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Th1598 details

Primary information
ID	15456
Therapeutic ID	Th1598
Protein Name	Galcanezumab
Sequence	>Th1598_Galcanezumab QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVYIQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG
Molecular Weight	147000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The mean serum half-life of galcanezumab is similar at all dose levels at about 25-30 days.[A33112] The elimination half-life of galcanezumab was ultimately approximately 27 days.[L4894]
Description	LY2951742/galcanezumab is a fully humanized monoclonal antibody against human calcitonin gene-related peptide (CGRP) that is developed by ELi Lilly and Company.[A33105] This therapy is given as a single subcutaneous injection twice a month and ongoing clinical trials for the agent are for episodic and chronic migraine as well as cluster headaches.[A33114] Although various small-molecule CGRP receptor antagonists have also been developed, humanized monoclonal antibodies like galcanezumab are specifically designed to potently and selectively bind to the CGRP entities directly.[A33112] Given this target specificity, lack of off-target toxicity, and characteristic proteolysis profile of immunoglobulin antibodies to not undergo metabolism by liver enzymes, galcanezumab possesses favourable and promising safety and tolerability.[A33112] Galcanezumab was given FDA approval on 27 September 2018.[L4894]
Indication/Disease	Galcanezumab is a humanized monoclonal antibody that is indicated for migraine prophylaxis and treatment of episodic cluster headaches in adults by binding endogenous human calcitonin gene-related peptide (CGRP).[A33112,L4894]
Pharmacodynamics	Galcanezumab is administered as a subcutaneous injection.[A33112,A33114,L4894] During clinical trials, it was noted that galcanezumab therapy resulted in a significant reduction in the mean number of migraine headache days and a good tolerability profile.[A33105] Additionally, post hoc efficacy analyses showed that 32% in the galcanezumab group versus 18% in the placebo group were complete responders.[A33105] Finally, the most commonly reported adverse events associated with galcanezumab use are headache, nasopharyngitis, hematuria, dermatitis, diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112]
Mechanism of Action	Galcanezumab is a fully humanized monoclonal antibody designed and manufactured specifically against calcitonin gene-related peptide (CGRP).[A33105,L4894] It binds avidly to human CGRP, with a binding affinity (Kd) of 31 pM (4.5 ng/mL). Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy.[A33090] Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients.[A33090] For all these reasons, the binding of CGRP to interfere with its activity was specifically designed to be the mechanism of action for galcanezumab to take advantage of in reversing the migraine-inducing activity of natural CGRP. The binding of galcanezumab to natural endogenous CGRP subsequently interferes with its activities, such as its binding to CGRP receptors, for example. Studies have also shown that humanized monoclonal antibodies against CGRP have proven successful in reducing the frequency of migraine headaches in early clinical trials as a preventative therapeutic.[A33112]
Toxicity	Overdose and LD₅₀ date are not readily available.[L4894] The most common adverse effects associated with galcanezumab during clinical trials include headache, nasopharyngitis, hematuria, and contact dermatitis.[A33112] However, with the exception of hematuria which was not present in placebo treatment arms, the frequencies of these events were similar to placebo.[A33112] Additional frequently reported adverse effects in subjects receiving galcanezumab were diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112] The pharmacokinetics of galcanezumab were not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), based on a population pharmacokinetic analysis.[L4894] Body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab.[L4894] Renal and hepatic impairment are not expected to affect the pharmacokinetics of galcanezumab.[L4894] Population pharmacokinetic analysis of integrated data from the galcanezumab clinical studies revealed that creatinine clearance did not affect the pharmacokinetics of galcanezumab in patients with mild or moderate renal impairment.[L4894] Patients with severe renal impairment (creatinine clearance <30 mL/min) have not been studied.[L4894] Based on a population PK analysis, bilirubin concentration did not significantly influence the CL/F of galcanezumab.[L4894] Studies regarding the carcinogenic potential and genetic toxicology of galcanezumab have not yet been conducted.[L4894] When galcanezumab (0, 30, or 250 mg/kg) was administered to male rats by subcutaneous injection prior to and during mating, no adverse effects on fertility was observed.[L4894] The higher dose tested was associated with a plasma exposure (Cave, ss) 8 times that in humans at the recommended human dose (RHD) of 120 mg.[L4894] When galcanezumab was administered to female rats by subcutaneous injection in two studies (0, 30, or 100 mg/kg; 0 or 250 mg/kg) prior to and during mating and continuing throughout organogenesis, no adverse effects on fertility were observed.[L4894] The highest dose tested (250 mg/kg) was associated with a plasma Cave, ss 38 times that in humans at the RHD.[L4894]
Metabolism	Monoclonal antibody agents like galcanezumab are not expected to generate toxic metabolites as they generally undergo proteolysis to their constituent amino acids.[F94] In particular, after administration galcanezumab is specifically expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous immunoglobulins.[L4894] Galcanezumab is also not believed to be metabolized by liver enzymes - making drug-drug interactions relatively unlikely.[L4894]
Absorption	Following single dose subcutaneous administration, the time to maximum concentration was recorded as 5 days.[L4894] The injection site location did not appear to significantly influence the absorption of galcanezumab.[L4894] The Cmax and the area under the concentration-time curve from dosing to infinity (AUC (0-8)) are generally considered to be dose proportional over a dose range.[A33112]
	The apparent volume of distribution of galcanezumab is documented to be 7.3 L, with 34% inter-individual variability.[L4894]
Clearance	It is noted that the clearance of galcanezumab is by proteolysis.[A33112] The apparent clearance of galcanezumab was recorded as 0.008 L/h.[L4894]
Categories	Amino Acids, Peptides, and Proteins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Calcitonin gene-related peptide 1,Calcitonin gene-related peptide 2
Brand Name	Emgality
Company	Eli Lilly & Co. Ltd.
Brand Description	Eli Lilly & Co. Ltd.
Prescribed For	Subcutaneous
Chemical Name	120 mg / mL
Formulation	EMGALITY is contraindicated in patients with serious hypersensitivity to galcanezumab-gnlm or to any of the excipients [see WARNINGS AND PRECAUTIONS].
Physical Appearance	injection site reactions such as pain, redness, and itching
Route of Administration	Emgality is a calcitonin-gene related peptide antagonist. Emgality is a prescription medicine used to prevent migraine headaches in adults. Emgality is also used to treat cluster headache episodes in adults. It is not known if Emgality is safe and effective in children. Warnings Follow all directions...
Recommended Dosage	Emgality (galcanezumab-gnlm) is a calcitonin-gene related peptide antagonist indicated for the preventive treatment of migraine in adults.
Contraindication	NA
Side Effects	NA
Useful Link 1	Link
Useful Link 2	Link
Remarks	NA

Primary information
ID	15457
Therapeutic ID	Th1598
Protein Name	Galcanezumab
Sequence	>Th1598_Galcanezumab QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVYIQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG
Molecular Weight	147000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The mean serum half-life of galcanezumab is similar at all dose levels at about 25-30 days.[A33112] The elimination half-life of galcanezumab was ultimately approximately 27 days.[L4894]
Description	LY2951742/galcanezumab is a fully humanized monoclonal antibody against human calcitonin gene-related peptide (CGRP) that is developed by ELi Lilly and Company.[A33105] This therapy is given as a single subcutaneous injection twice a month and ongoing clinical trials for the agent are for episodic and chronic migraine as well as cluster headaches.[A33114] Although various small-molecule CGRP receptor antagonists have also been developed, humanized monoclonal antibodies like galcanezumab are specifically designed to potently and selectively bind to the CGRP entities directly.[A33112] Given this target specificity, lack of off-target toxicity, and characteristic proteolysis profile of immunoglobulin antibodies to not undergo metabolism by liver enzymes, galcanezumab possesses favourable and promising safety and tolerability.[A33112] Galcanezumab was given FDA approval on 27 September 2018.[L4894]
Indication/Disease	Galcanezumab is a humanized monoclonal antibody that is indicated for migraine prophylaxis and treatment of episodic cluster headaches in adults by binding endogenous human calcitonin gene-related peptide (CGRP).[A33112,L4894]
Pharmacodynamics	Galcanezumab is administered as a subcutaneous injection.[A33112,A33114,L4894] During clinical trials, it was noted that galcanezumab therapy resulted in a significant reduction in the mean number of migraine headache days and a good tolerability profile.[A33105] Additionally, post hoc efficacy analyses showed that 32% in the galcanezumab group versus 18% in the placebo group were complete responders.[A33105] Finally, the most commonly reported adverse events associated with galcanezumab use are headache, nasopharyngitis, hematuria, dermatitis, diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112]
Mechanism of Action	Galcanezumab is a fully humanized monoclonal antibody designed and manufactured specifically against calcitonin gene-related peptide (CGRP).[A33105,L4894] It binds avidly to human CGRP, with a binding affinity (Kd) of 31 pM (4.5 ng/mL). Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy.[A33090] Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients.[A33090] For all these reasons, the binding of CGRP to interfere with its activity was specifically designed to be the mechanism of action for galcanezumab to take advantage of in reversing the migraine-inducing activity of natural CGRP. The binding of galcanezumab to natural endogenous CGRP subsequently interferes with its activities, such as its binding to CGRP receptors, for example. Studies have also shown that humanized monoclonal antibodies against CGRP have proven successful in reducing the frequency of migraine headaches in early clinical trials as a preventative therapeutic.[A33112]
Toxicity	Overdose and LD₅₀ date are not readily available.[L4894] The most common adverse effects associated with galcanezumab during clinical trials include headache, nasopharyngitis, hematuria, and contact dermatitis.[A33112] However, with the exception of hematuria which was not present in placebo treatment arms, the frequencies of these events were similar to placebo.[A33112] Additional frequently reported adverse effects in subjects receiving galcanezumab were diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112] The pharmacokinetics of galcanezumab were not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), based on a population pharmacokinetic analysis.[L4894] Body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab.[L4894] Renal and hepatic impairment are not expected to affect the pharmacokinetics of galcanezumab.[L4894] Population pharmacokinetic analysis of integrated data from the galcanezumab clinical studies revealed that creatinine clearance did not affect the pharmacokinetics of galcanezumab in patients with mild or moderate renal impairment.[L4894] Patients with severe renal impairment (creatinine clearance <30 mL/min) have not been studied.[L4894] Based on a population PK analysis, bilirubin concentration did not significantly influence the CL/F of galcanezumab.[L4894] Studies regarding the carcinogenic potential and genetic toxicology of galcanezumab have not yet been conducted.[L4894] When galcanezumab (0, 30, or 250 mg/kg) was administered to male rats by subcutaneous injection prior to and during mating, no adverse effects on fertility was observed.[L4894] The higher dose tested was associated with a plasma exposure (Cave, ss) 8 times that in humans at the recommended human dose (RHD) of 120 mg.[L4894] When galcanezumab was administered to female rats by subcutaneous injection in two studies (0, 30, or 100 mg/kg; 0 or 250 mg/kg) prior to and during mating and continuing throughout organogenesis, no adverse effects on fertility were observed.[L4894] The highest dose tested (250 mg/kg) was associated with a plasma Cave, ss 38 times that in humans at the RHD.[L4894]
Metabolism	Monoclonal antibody agents like galcanezumab are not expected to generate toxic metabolites as they generally undergo proteolysis to their constituent amino acids.[F94] In particular, after administration galcanezumab is specifically expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous immunoglobulins.[L4894] Galcanezumab is also not believed to be metabolized by liver enzymes - making drug-drug interactions relatively unlikely.[L4894]
Absorption	Following single dose subcutaneous administration, the time to maximum concentration was recorded as 5 days.[L4894] The injection site location did not appear to significantly influence the absorption of galcanezumab.[L4894] The Cmax and the area under the concentration-time curve from dosing to infinity (AUC (0-8)) are generally considered to be dose proportional over a dose range.[A33112]
	The apparent volume of distribution of galcanezumab is documented to be 7.3 L, with 34% inter-individual variability.[L4894]
Clearance	It is noted that the clearance of galcanezumab is by proteolysis.[A33112] The apparent clearance of galcanezumab was recorded as 0.008 L/h.[L4894]
Categories	Analgesics
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Calcitonin gene-related peptide 1,Calcitonin gene-related peptide 2
Brand Name	Emgality
Company	Eli Lilly & Co. Ltd.
Brand Description	Eli Lilly & Co. Ltd.
Prescribed For	Subcutaneous
Chemical Name	100 mg / mL
Formulation	EMGALITY is contraindicated in patients with serious hypersensitivity to galcanezumab-gnlm or to any of the excipients [see WARNINGS AND PRECAUTIONS].
Physical Appearance	injection site reactions such as pain, redness, and itching
Route of Administration	Emgality is a calcitonin-gene related peptide antagonist. Emgality is a prescription medicine used to prevent migraine headaches in adults. Emgality is also used to treat cluster headache episodes in adults. It is not known if Emgality is safe and effective in children. Warnings Follow all directions...
Recommended Dosage	Emgality (galcanezumab-gnlm) is a calcitonin-gene related peptide antagonist indicated for the preventive treatment of migraine in adults.
Contraindication	NA
Side Effects	NA
Useful Link 1	Link
Useful Link 2	Link
Remarks	NA

Primary information
ID	15458
Therapeutic ID	Th1598
Protein Name	Galcanezumab
Sequence	>Th1598_Galcanezumab QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVYIQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG
Molecular Weight	147000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The mean serum half-life of galcanezumab is similar at all dose levels at about 25-30 days.[A33112] The elimination half-life of galcanezumab was ultimately approximately 27 days.[L4894]
Description	LY2951742/galcanezumab is a fully humanized monoclonal antibody against human calcitonin gene-related peptide (CGRP) that is developed by ELi Lilly and Company.[A33105] This therapy is given as a single subcutaneous injection twice a month and ongoing clinical trials for the agent are for episodic and chronic migraine as well as cluster headaches.[A33114] Although various small-molecule CGRP receptor antagonists have also been developed, humanized monoclonal antibodies like galcanezumab are specifically designed to potently and selectively bind to the CGRP entities directly.[A33112] Given this target specificity, lack of off-target toxicity, and characteristic proteolysis profile of immunoglobulin antibodies to not undergo metabolism by liver enzymes, galcanezumab possesses favourable and promising safety and tolerability.[A33112] Galcanezumab was given FDA approval on 27 September 2018.[L4894]
Indication/Disease	Galcanezumab is a humanized monoclonal antibody that is indicated for migraine prophylaxis and treatment of episodic cluster headaches in adults by binding endogenous human calcitonin gene-related peptide (CGRP).[A33112,L4894]
Pharmacodynamics	Galcanezumab is administered as a subcutaneous injection.[A33112,A33114,L4894] During clinical trials, it was noted that galcanezumab therapy resulted in a significant reduction in the mean number of migraine headache days and a good tolerability profile.[A33105] Additionally, post hoc efficacy analyses showed that 32% in the galcanezumab group versus 18% in the placebo group were complete responders.[A33105] Finally, the most commonly reported adverse events associated with galcanezumab use are headache, nasopharyngitis, hematuria, dermatitis, diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112]
Mechanism of Action	Galcanezumab is a fully humanized monoclonal antibody designed and manufactured specifically against calcitonin gene-related peptide (CGRP).[A33105,L4894] It binds avidly to human CGRP, with a binding affinity (Kd) of 31 pM (4.5 ng/mL). Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy.[A33090] Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients.[A33090] For all these reasons, the binding of CGRP to interfere with its activity was specifically designed to be the mechanism of action for galcanezumab to take advantage of in reversing the migraine-inducing activity of natural CGRP. The binding of galcanezumab to natural endogenous CGRP subsequently interferes with its activities, such as its binding to CGRP receptors, for example. Studies have also shown that humanized monoclonal antibodies against CGRP have proven successful in reducing the frequency of migraine headaches in early clinical trials as a preventative therapeutic.[A33112]
Toxicity	Overdose and LD₅₀ date are not readily available.[L4894] The most common adverse effects associated with galcanezumab during clinical trials include headache, nasopharyngitis, hematuria, and contact dermatitis.[A33112] However, with the exception of hematuria which was not present in placebo treatment arms, the frequencies of these events were similar to placebo.[A33112] Additional frequently reported adverse effects in subjects receiving galcanezumab were diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112] The pharmacokinetics of galcanezumab were not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), based on a population pharmacokinetic analysis.[L4894] Body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab.[L4894] Renal and hepatic impairment are not expected to affect the pharmacokinetics of galcanezumab.[L4894] Population pharmacokinetic analysis of integrated data from the galcanezumab clinical studies revealed that creatinine clearance did not affect the pharmacokinetics of galcanezumab in patients with mild or moderate renal impairment.[L4894] Patients with severe renal impairment (creatinine clearance <30 mL/min) have not been studied.[L4894] Based on a population PK analysis, bilirubin concentration did not significantly influence the CL/F of galcanezumab.[L4894] Studies regarding the carcinogenic potential and genetic toxicology of galcanezumab have not yet been conducted.[L4894] When galcanezumab (0, 30, or 250 mg/kg) was administered to male rats by subcutaneous injection prior to and during mating, no adverse effects on fertility was observed.[L4894] The higher dose tested was associated with a plasma exposure (Cave, ss) 8 times that in humans at the recommended human dose (RHD) of 120 mg.[L4894] When galcanezumab was administered to female rats by subcutaneous injection in two studies (0, 30, or 100 mg/kg; 0 or 250 mg/kg) prior to and during mating and continuing throughout organogenesis, no adverse effects on fertility were observed.[L4894] The highest dose tested (250 mg/kg) was associated with a plasma Cave, ss 38 times that in humans at the RHD.[L4894]
Metabolism	Monoclonal antibody agents like galcanezumab are not expected to generate toxic metabolites as they generally undergo proteolysis to their constituent amino acids.[F94] In particular, after administration galcanezumab is specifically expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous immunoglobulins.[L4894] Galcanezumab is also not believed to be metabolized by liver enzymes - making drug-drug interactions relatively unlikely.[L4894]
Absorption	Following single dose subcutaneous administration, the time to maximum concentration was recorded as 5 days.[L4894] The injection site location did not appear to significantly influence the absorption of galcanezumab.[L4894] The Cmax and the area under the concentration-time curve from dosing to infinity (AUC (0-8)) are generally considered to be dose proportional over a dose range.[A33112]
	The apparent volume of distribution of galcanezumab is documented to be 7.3 L, with 34% inter-individual variability.[L4894]
Clearance	It is noted that the clearance of galcanezumab is by proteolysis.[A33112] The apparent clearance of galcanezumab was recorded as 0.008 L/h.[L4894]
Categories	Antibodies
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Calcitonin gene-related peptide 1,Calcitonin gene-related peptide 2
Brand Name	Emgality
Company	Eli Lilly and Company
Brand Description	Eli Lilly and Company
Prescribed For	Subcutaneous
Chemical Name	120 mg/1mL
Formulation	EMGALITY is contraindicated in patients with serious hypersensitivity to galcanezumab-gnlm or to any of the excipients [see WARNINGS AND PRECAUTIONS].
Physical Appearance	injection site reactions such as pain, redness, and itching
Route of Administration	Emgality is a calcitonin-gene related peptide antagonist. Emgality is a prescription medicine used to prevent migraine headaches in adults. Emgality is also used to treat cluster headache episodes in adults. It is not known if Emgality is safe and effective in children. Warnings Follow all directions...
Recommended Dosage	Emgality (galcanezumab-gnlm) is a calcitonin-gene related peptide antagonist indicated for the preventive treatment of migraine in adults.
Contraindication	NA
Side Effects	NA
Useful Link 1	Link
Useful Link 2	Link
Remarks	NA

Primary information
ID	15459
Therapeutic ID	Th1598
Protein Name	Galcanezumab
Sequence	>Th1598_Galcanezumab QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVYIQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG
Molecular Weight	147000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The mean serum half-life of galcanezumab is similar at all dose levels at about 25-30 days.[A33112] The elimination half-life of galcanezumab was ultimately approximately 27 days.[L4894]
Description	LY2951742/galcanezumab is a fully humanized monoclonal antibody against human calcitonin gene-related peptide (CGRP) that is developed by ELi Lilly and Company.[A33105] This therapy is given as a single subcutaneous injection twice a month and ongoing clinical trials for the agent are for episodic and chronic migraine as well as cluster headaches.[A33114] Although various small-molecule CGRP receptor antagonists have also been developed, humanized monoclonal antibodies like galcanezumab are specifically designed to potently and selectively bind to the CGRP entities directly.[A33112] Given this target specificity, lack of off-target toxicity, and characteristic proteolysis profile of immunoglobulin antibodies to not undergo metabolism by liver enzymes, galcanezumab possesses favourable and promising safety and tolerability.[A33112] Galcanezumab was given FDA approval on 27 September 2018.[L4894]
Indication/Disease	Galcanezumab is a humanized monoclonal antibody that is indicated for migraine prophylaxis and treatment of episodic cluster headaches in adults by binding endogenous human calcitonin gene-related peptide (CGRP).[A33112,L4894]
Pharmacodynamics	Galcanezumab is administered as a subcutaneous injection.[A33112,A33114,L4894] During clinical trials, it was noted that galcanezumab therapy resulted in a significant reduction in the mean number of migraine headache days and a good tolerability profile.[A33105] Additionally, post hoc efficacy analyses showed that 32% in the galcanezumab group versus 18% in the placebo group were complete responders.[A33105] Finally, the most commonly reported adverse events associated with galcanezumab use are headache, nasopharyngitis, hematuria, dermatitis, diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112]
Mechanism of Action	Galcanezumab is a fully humanized monoclonal antibody designed and manufactured specifically against calcitonin gene-related peptide (CGRP).[A33105,L4894] It binds avidly to human CGRP, with a binding affinity (Kd) of 31 pM (4.5 ng/mL). Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy.[A33090] Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients.[A33090] For all these reasons, the binding of CGRP to interfere with its activity was specifically designed to be the mechanism of action for galcanezumab to take advantage of in reversing the migraine-inducing activity of natural CGRP. The binding of galcanezumab to natural endogenous CGRP subsequently interferes with its activities, such as its binding to CGRP receptors, for example. Studies have also shown that humanized monoclonal antibodies against CGRP have proven successful in reducing the frequency of migraine headaches in early clinical trials as a preventative therapeutic.[A33112]
Toxicity	Overdose and LD₅₀ date are not readily available.[L4894] The most common adverse effects associated with galcanezumab during clinical trials include headache, nasopharyngitis, hematuria, and contact dermatitis.[A33112] However, with the exception of hematuria which was not present in placebo treatment arms, the frequencies of these events were similar to placebo.[A33112] Additional frequently reported adverse effects in subjects receiving galcanezumab were diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112] The pharmacokinetics of galcanezumab were not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), based on a population pharmacokinetic analysis.[L4894] Body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab.[L4894] Renal and hepatic impairment are not expected to affect the pharmacokinetics of galcanezumab.[L4894] Population pharmacokinetic analysis of integrated data from the galcanezumab clinical studies revealed that creatinine clearance did not affect the pharmacokinetics of galcanezumab in patients with mild or moderate renal impairment.[L4894] Patients with severe renal impairment (creatinine clearance <30 mL/min) have not been studied.[L4894] Based on a population PK analysis, bilirubin concentration did not significantly influence the CL/F of galcanezumab.[L4894] Studies regarding the carcinogenic potential and genetic toxicology of galcanezumab have not yet been conducted.[L4894] When galcanezumab (0, 30, or 250 mg/kg) was administered to male rats by subcutaneous injection prior to and during mating, no adverse effects on fertility was observed.[L4894] The higher dose tested was associated with a plasma exposure (Cave, ss) 8 times that in humans at the recommended human dose (RHD) of 120 mg.[L4894] When galcanezumab was administered to female rats by subcutaneous injection in two studies (0, 30, or 100 mg/kg; 0 or 250 mg/kg) prior to and during mating and continuing throughout organogenesis, no adverse effects on fertility were observed.[L4894] The highest dose tested (250 mg/kg) was associated with a plasma Cave, ss 38 times that in humans at the RHD.[L4894]
Metabolism	Monoclonal antibody agents like galcanezumab are not expected to generate toxic metabolites as they generally undergo proteolysis to their constituent amino acids.[F94] In particular, after administration galcanezumab is specifically expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous immunoglobulins.[L4894] Galcanezumab is also not believed to be metabolized by liver enzymes - making drug-drug interactions relatively unlikely.[L4894]
Absorption	Following single dose subcutaneous administration, the time to maximum concentration was recorded as 5 days.[L4894] The injection site location did not appear to significantly influence the absorption of galcanezumab.[L4894] The Cmax and the area under the concentration-time curve from dosing to infinity (AUC (0-8)) are generally considered to be dose proportional over a dose range.[A33112]
	The apparent volume of distribution of galcanezumab is documented to be 7.3 L, with 34% inter-individual variability.[L4894]
Clearance	It is noted that the clearance of galcanezumab is by proteolysis.[A33112] The apparent clearance of galcanezumab was recorded as 0.008 L/h.[L4894]
Categories	Antibodies, Monoclonal
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Calcitonin gene-related peptide 1,Calcitonin gene-related peptide 2
Brand Name	Emgality
Company	Eli Lilly Nederland B.V.
Brand Description	Eli Lilly Nederland B.V.
Prescribed For	Subcutaneous
Chemical Name	120 mg
Formulation	EMGALITY is contraindicated in patients with serious hypersensitivity to galcanezumab-gnlm or to any of the excipients [see WARNINGS AND PRECAUTIONS].
Physical Appearance	injection site reactions such as pain, redness, and itching
Route of Administration	Emgality is a calcitonin-gene related peptide antagonist. Emgality is a prescription medicine used to prevent migraine headaches in adults. Emgality is also used to treat cluster headache episodes in adults. It is not known if Emgality is safe and effective in children. Warnings Follow all directions...
Recommended Dosage	Emgality (galcanezumab-gnlm) is a calcitonin-gene related peptide antagonist indicated for the preventive treatment of migraine in adults.
Contraindication	NA
Side Effects	NA
Useful Link 1	Link
Useful Link 2	Link
Remarks	NA

Primary information
ID	15460
Therapeutic ID	Th1598
Protein Name	Galcanezumab
Sequence	>Th1598_Galcanezumab QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVYIQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG
Molecular Weight	147000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The mean serum half-life of galcanezumab is similar at all dose levels at about 25-30 days.[A33112] The elimination half-life of galcanezumab was ultimately approximately 27 days.[L4894]
Description	LY2951742/galcanezumab is a fully humanized monoclonal antibody against human calcitonin gene-related peptide (CGRP) that is developed by ELi Lilly and Company.[A33105] This therapy is given as a single subcutaneous injection twice a month and ongoing clinical trials for the agent are for episodic and chronic migraine as well as cluster headaches.[A33114] Although various small-molecule CGRP receptor antagonists have also been developed, humanized monoclonal antibodies like galcanezumab are specifically designed to potently and selectively bind to the CGRP entities directly.[A33112] Given this target specificity, lack of off-target toxicity, and characteristic proteolysis profile of immunoglobulin antibodies to not undergo metabolism by liver enzymes, galcanezumab possesses favourable and promising safety and tolerability.[A33112] Galcanezumab was given FDA approval on 27 September 2018.[L4894]
Indication/Disease	Galcanezumab is a humanized monoclonal antibody that is indicated for migraine prophylaxis and treatment of episodic cluster headaches in adults by binding endogenous human calcitonin gene-related peptide (CGRP).[A33112,L4894]
Pharmacodynamics	Galcanezumab is administered as a subcutaneous injection.[A33112,A33114,L4894] During clinical trials, it was noted that galcanezumab therapy resulted in a significant reduction in the mean number of migraine headache days and a good tolerability profile.[A33105] Additionally, post hoc efficacy analyses showed that 32% in the galcanezumab group versus 18% in the placebo group were complete responders.[A33105] Finally, the most commonly reported adverse events associated with galcanezumab use are headache, nasopharyngitis, hematuria, dermatitis, diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112]
Mechanism of Action	Galcanezumab is a fully humanized monoclonal antibody designed and manufactured specifically against calcitonin gene-related peptide (CGRP).[A33105,L4894] It binds avidly to human CGRP, with a binding affinity (Kd) of 31 pM (4.5 ng/mL). Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy.[A33090] Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients.[A33090] For all these reasons, the binding of CGRP to interfere with its activity was specifically designed to be the mechanism of action for galcanezumab to take advantage of in reversing the migraine-inducing activity of natural CGRP. The binding of galcanezumab to natural endogenous CGRP subsequently interferes with its activities, such as its binding to CGRP receptors, for example. Studies have also shown that humanized monoclonal antibodies against CGRP have proven successful in reducing the frequency of migraine headaches in early clinical trials as a preventative therapeutic.[A33112]
Toxicity	Overdose and LD₅₀ date are not readily available.[L4894] The most common adverse effects associated with galcanezumab during clinical trials include headache, nasopharyngitis, hematuria, and contact dermatitis.[A33112] However, with the exception of hematuria which was not present in placebo treatment arms, the frequencies of these events were similar to placebo.[A33112] Additional frequently reported adverse effects in subjects receiving galcanezumab were diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112] The pharmacokinetics of galcanezumab were not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), based on a population pharmacokinetic analysis.[L4894] Body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab.[L4894] Renal and hepatic impairment are not expected to affect the pharmacokinetics of galcanezumab.[L4894] Population pharmacokinetic analysis of integrated data from the galcanezumab clinical studies revealed that creatinine clearance did not affect the pharmacokinetics of galcanezumab in patients with mild or moderate renal impairment.[L4894] Patients with severe renal impairment (creatinine clearance <30 mL/min) have not been studied.[L4894] Based on a population PK analysis, bilirubin concentration did not significantly influence the CL/F of galcanezumab.[L4894] Studies regarding the carcinogenic potential and genetic toxicology of galcanezumab have not yet been conducted.[L4894] When galcanezumab (0, 30, or 250 mg/kg) was administered to male rats by subcutaneous injection prior to and during mating, no adverse effects on fertility was observed.[L4894] The higher dose tested was associated with a plasma exposure (Cave, ss) 8 times that in humans at the recommended human dose (RHD) of 120 mg.[L4894] When galcanezumab was administered to female rats by subcutaneous injection in two studies (0, 30, or 100 mg/kg; 0 or 250 mg/kg) prior to and during mating and continuing throughout organogenesis, no adverse effects on fertility were observed.[L4894] The highest dose tested (250 mg/kg) was associated with a plasma Cave, ss 38 times that in humans at the RHD.[L4894]
Metabolism	Monoclonal antibody agents like galcanezumab are not expected to generate toxic metabolites as they generally undergo proteolysis to their constituent amino acids.[F94] In particular, after administration galcanezumab is specifically expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous immunoglobulins.[L4894] Galcanezumab is also not believed to be metabolized by liver enzymes - making drug-drug interactions relatively unlikely.[L4894]
Absorption	Following single dose subcutaneous administration, the time to maximum concentration was recorded as 5 days.[L4894] The injection site location did not appear to significantly influence the absorption of galcanezumab.[L4894] The Cmax and the area under the concentration-time curve from dosing to infinity (AUC (0-8)) are generally considered to be dose proportional over a dose range.[A33112]
	The apparent volume of distribution of galcanezumab is documented to be 7.3 L, with 34% inter-individual variability.[L4894]
Clearance	It is noted that the clearance of galcanezumab is by proteolysis.[A33112] The apparent clearance of galcanezumab was recorded as 0.008 L/h.[L4894]
Categories	Antibodies, Monoclonal, Humanized
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Calcitonin gene-related peptide 1,Calcitonin gene-related peptide 2
Brand Name	Emgality
Company	Eli Lilly and Company
Brand Description	Eli Lilly and Company
Prescribed For	Subcutaneous
Chemical Name	100 mg/1mL
Formulation	EMGALITY is contraindicated in patients with serious hypersensitivity to galcanezumab-gnlm or to any of the excipients [see WARNINGS AND PRECAUTIONS].
Physical Appearance	injection site reactions such as pain, redness, and itching
Route of Administration	Emgality is a calcitonin-gene related peptide antagonist. Emgality is a prescription medicine used to prevent migraine headaches in adults. Emgality is also used to treat cluster headache episodes in adults. It is not known if Emgality is safe and effective in children. Warnings Follow all directions...
Recommended Dosage	Emgality (galcanezumab-gnlm) is a calcitonin-gene related peptide antagonist indicated for the preventive treatment of migraine in adults.
Contraindication	NA
Side Effects	NA
Useful Link 1	Link
Useful Link 2	Link
Remarks	NA

Primary information
ID	15461
Therapeutic ID	Th1598
Protein Name	Galcanezumab
Sequence	>Th1598_Galcanezumab QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVYIQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG
Molecular Weight	147000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The mean serum half-life of galcanezumab is similar at all dose levels at about 25-30 days.[A33112] The elimination half-life of galcanezumab was ultimately approximately 27 days.[L4894]
Description	LY2951742/galcanezumab is a fully humanized monoclonal antibody against human calcitonin gene-related peptide (CGRP) that is developed by ELi Lilly and Company.[A33105] This therapy is given as a single subcutaneous injection twice a month and ongoing clinical trials for the agent are for episodic and chronic migraine as well as cluster headaches.[A33114] Although various small-molecule CGRP receptor antagonists have also been developed, humanized monoclonal antibodies like galcanezumab are specifically designed to potently and selectively bind to the CGRP entities directly.[A33112] Given this target specificity, lack of off-target toxicity, and characteristic proteolysis profile of immunoglobulin antibodies to not undergo metabolism by liver enzymes, galcanezumab possesses favourable and promising safety and tolerability.[A33112] Galcanezumab was given FDA approval on 27 September 2018.[L4894]
Indication/Disease	Galcanezumab is a humanized monoclonal antibody that is indicated for migraine prophylaxis and treatment of episodic cluster headaches in adults by binding endogenous human calcitonin gene-related peptide (CGRP).[A33112,L4894]
Pharmacodynamics	Galcanezumab is administered as a subcutaneous injection.[A33112,A33114,L4894] During clinical trials, it was noted that galcanezumab therapy resulted in a significant reduction in the mean number of migraine headache days and a good tolerability profile.[A33105] Additionally, post hoc efficacy analyses showed that 32% in the galcanezumab group versus 18% in the placebo group were complete responders.[A33105] Finally, the most commonly reported adverse events associated with galcanezumab use are headache, nasopharyngitis, hematuria, dermatitis, diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112]
Mechanism of Action	Galcanezumab is a fully humanized monoclonal antibody designed and manufactured specifically against calcitonin gene-related peptide (CGRP).[A33105,L4894] It binds avidly to human CGRP, with a binding affinity (Kd) of 31 pM (4.5 ng/mL). Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy.[A33090] Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients.[A33090] For all these reasons, the binding of CGRP to interfere with its activity was specifically designed to be the mechanism of action for galcanezumab to take advantage of in reversing the migraine-inducing activity of natural CGRP. The binding of galcanezumab to natural endogenous CGRP subsequently interferes with its activities, such as its binding to CGRP receptors, for example. Studies have also shown that humanized monoclonal antibodies against CGRP have proven successful in reducing the frequency of migraine headaches in early clinical trials as a preventative therapeutic.[A33112]
Toxicity	Overdose and LD₅₀ date are not readily available.[L4894] The most common adverse effects associated with galcanezumab during clinical trials include headache, nasopharyngitis, hematuria, and contact dermatitis.[A33112] However, with the exception of hematuria which was not present in placebo treatment arms, the frequencies of these events were similar to placebo.[A33112] Additional frequently reported adverse effects in subjects receiving galcanezumab were diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112] The pharmacokinetics of galcanezumab were not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), based on a population pharmacokinetic analysis.[L4894] Body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab.[L4894] Renal and hepatic impairment are not expected to affect the pharmacokinetics of galcanezumab.[L4894] Population pharmacokinetic analysis of integrated data from the galcanezumab clinical studies revealed that creatinine clearance did not affect the pharmacokinetics of galcanezumab in patients with mild or moderate renal impairment.[L4894] Patients with severe renal impairment (creatinine clearance <30 mL/min) have not been studied.[L4894] Based on a population PK analysis, bilirubin concentration did not significantly influence the CL/F of galcanezumab.[L4894] Studies regarding the carcinogenic potential and genetic toxicology of galcanezumab have not yet been conducted.[L4894] When galcanezumab (0, 30, or 250 mg/kg) was administered to male rats by subcutaneous injection prior to and during mating, no adverse effects on fertility was observed.[L4894] The higher dose tested was associated with a plasma exposure (Cave, ss) 8 times that in humans at the recommended human dose (RHD) of 120 mg.[L4894] When galcanezumab was administered to female rats by subcutaneous injection in two studies (0, 30, or 100 mg/kg; 0 or 250 mg/kg) prior to and during mating and continuing throughout organogenesis, no adverse effects on fertility were observed.[L4894] The highest dose tested (250 mg/kg) was associated with a plasma Cave, ss 38 times that in humans at the RHD.[L4894]
Metabolism	Monoclonal antibody agents like galcanezumab are not expected to generate toxic metabolites as they generally undergo proteolysis to their constituent amino acids.[F94] In particular, after administration galcanezumab is specifically expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous immunoglobulins.[L4894] Galcanezumab is also not believed to be metabolized by liver enzymes - making drug-drug interactions relatively unlikely.[L4894]
Absorption	Following single dose subcutaneous administration, the time to maximum concentration was recorded as 5 days.[L4894] The injection site location did not appear to significantly influence the absorption of galcanezumab.[L4894] The Cmax and the area under the concentration-time curve from dosing to infinity (AUC (0-8)) are generally considered to be dose proportional over a dose range.[A33112]
	The apparent volume of distribution of galcanezumab is documented to be 7.3 L, with 34% inter-individual variability.[L4894]
Clearance	It is noted that the clearance of galcanezumab is by proteolysis.[A33112] The apparent clearance of galcanezumab was recorded as 0.008 L/h.[L4894]
Categories	Antimigraine Preparations
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Calcitonin gene-related peptide 1,Calcitonin gene-related peptide 2
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	NA
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15462
Therapeutic ID	Th1598
Protein Name	Galcanezumab
Sequence	>Th1598_Galcanezumab QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVYIQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG
Molecular Weight	147000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The mean serum half-life of galcanezumab is similar at all dose levels at about 25-30 days.[A33112] The elimination half-life of galcanezumab was ultimately approximately 27 days.[L4894]
Description	LY2951742/galcanezumab is a fully humanized monoclonal antibody against human calcitonin gene-related peptide (CGRP) that is developed by ELi Lilly and Company.[A33105] This therapy is given as a single subcutaneous injection twice a month and ongoing clinical trials for the agent are for episodic and chronic migraine as well as cluster headaches.[A33114] Although various small-molecule CGRP receptor antagonists have also been developed, humanized monoclonal antibodies like galcanezumab are specifically designed to potently and selectively bind to the CGRP entities directly.[A33112] Given this target specificity, lack of off-target toxicity, and characteristic proteolysis profile of immunoglobulin antibodies to not undergo metabolism by liver enzymes, galcanezumab possesses favourable and promising safety and tolerability.[A33112] Galcanezumab was given FDA approval on 27 September 2018.[L4894]
Indication/Disease	Galcanezumab is a humanized monoclonal antibody that is indicated for migraine prophylaxis and treatment of episodic cluster headaches in adults by binding endogenous human calcitonin gene-related peptide (CGRP).[A33112,L4894]
Pharmacodynamics	Galcanezumab is administered as a subcutaneous injection.[A33112,A33114,L4894] During clinical trials, it was noted that galcanezumab therapy resulted in a significant reduction in the mean number of migraine headache days and a good tolerability profile.[A33105] Additionally, post hoc efficacy analyses showed that 32% in the galcanezumab group versus 18% in the placebo group were complete responders.[A33105] Finally, the most commonly reported adverse events associated with galcanezumab use are headache, nasopharyngitis, hematuria, dermatitis, diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112]
Mechanism of Action	Galcanezumab is a fully humanized monoclonal antibody designed and manufactured specifically against calcitonin gene-related peptide (CGRP).[A33105,L4894] It binds avidly to human CGRP, with a binding affinity (Kd) of 31 pM (4.5 ng/mL). Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy.[A33090] Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients.[A33090] For all these reasons, the binding of CGRP to interfere with its activity was specifically designed to be the mechanism of action for galcanezumab to take advantage of in reversing the migraine-inducing activity of natural CGRP. The binding of galcanezumab to natural endogenous CGRP subsequently interferes with its activities, such as its binding to CGRP receptors, for example. Studies have also shown that humanized monoclonal antibodies against CGRP have proven successful in reducing the frequency of migraine headaches in early clinical trials as a preventative therapeutic.[A33112]
Toxicity	Overdose and LD₅₀ date are not readily available.[L4894] The most common adverse effects associated with galcanezumab during clinical trials include headache, nasopharyngitis, hematuria, and contact dermatitis.[A33112] However, with the exception of hematuria which was not present in placebo treatment arms, the frequencies of these events were similar to placebo.[A33112] Additional frequently reported adverse effects in subjects receiving galcanezumab were diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112] The pharmacokinetics of galcanezumab were not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), based on a population pharmacokinetic analysis.[L4894] Body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab.[L4894] Renal and hepatic impairment are not expected to affect the pharmacokinetics of galcanezumab.[L4894] Population pharmacokinetic analysis of integrated data from the galcanezumab clinical studies revealed that creatinine clearance did not affect the pharmacokinetics of galcanezumab in patients with mild or moderate renal impairment.[L4894] Patients with severe renal impairment (creatinine clearance <30 mL/min) have not been studied.[L4894] Based on a population PK analysis, bilirubin concentration did not significantly influence the CL/F of galcanezumab.[L4894] Studies regarding the carcinogenic potential and genetic toxicology of galcanezumab have not yet been conducted.[L4894] When galcanezumab (0, 30, or 250 mg/kg) was administered to male rats by subcutaneous injection prior to and during mating, no adverse effects on fertility was observed.[L4894] The higher dose tested was associated with a plasma exposure (Cave, ss) 8 times that in humans at the recommended human dose (RHD) of 120 mg.[L4894] When galcanezumab was administered to female rats by subcutaneous injection in two studies (0, 30, or 100 mg/kg; 0 or 250 mg/kg) prior to and during mating and continuing throughout organogenesis, no adverse effects on fertility were observed.[L4894] The highest dose tested (250 mg/kg) was associated with a plasma Cave, ss 38 times that in humans at the RHD.[L4894]
Metabolism	Monoclonal antibody agents like galcanezumab are not expected to generate toxic metabolites as they generally undergo proteolysis to their constituent amino acids.[F94] In particular, after administration galcanezumab is specifically expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous immunoglobulins.[L4894] Galcanezumab is also not believed to be metabolized by liver enzymes - making drug-drug interactions relatively unlikely.[L4894]
Absorption	Following single dose subcutaneous administration, the time to maximum concentration was recorded as 5 days.[L4894] The injection site location did not appear to significantly influence the absorption of galcanezumab.[L4894] The Cmax and the area under the concentration-time curve from dosing to infinity (AUC (0-8)) are generally considered to be dose proportional over a dose range.[A33112]
	The apparent volume of distribution of galcanezumab is documented to be 7.3 L, with 34% inter-individual variability.[L4894]
Clearance	It is noted that the clearance of galcanezumab is by proteolysis.[A33112] The apparent clearance of galcanezumab was recorded as 0.008 L/h.[L4894]
Categories	Blood Proteins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Calcitonin gene-related peptide 1,Calcitonin gene-related peptide 2
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	NA
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15463
Therapeutic ID	Th1598
Protein Name	Galcanezumab
Sequence	>Th1598_Galcanezumab QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVYIQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG
Molecular Weight	147000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The mean serum half-life of galcanezumab is similar at all dose levels at about 25-30 days.[A33112] The elimination half-life of galcanezumab was ultimately approximately 27 days.[L4894]
Description	LY2951742/galcanezumab is a fully humanized monoclonal antibody against human calcitonin gene-related peptide (CGRP) that is developed by ELi Lilly and Company.[A33105] This therapy is given as a single subcutaneous injection twice a month and ongoing clinical trials for the agent are for episodic and chronic migraine as well as cluster headaches.[A33114] Although various small-molecule CGRP receptor antagonists have also been developed, humanized monoclonal antibodies like galcanezumab are specifically designed to potently and selectively bind to the CGRP entities directly.[A33112] Given this target specificity, lack of off-target toxicity, and characteristic proteolysis profile of immunoglobulin antibodies to not undergo metabolism by liver enzymes, galcanezumab possesses favourable and promising safety and tolerability.[A33112] Galcanezumab was given FDA approval on 27 September 2018.[L4894]
Indication/Disease	Galcanezumab is a humanized monoclonal antibody that is indicated for migraine prophylaxis and treatment of episodic cluster headaches in adults by binding endogenous human calcitonin gene-related peptide (CGRP).[A33112,L4894]
Pharmacodynamics	Galcanezumab is administered as a subcutaneous injection.[A33112,A33114,L4894] During clinical trials, it was noted that galcanezumab therapy resulted in a significant reduction in the mean number of migraine headache days and a good tolerability profile.[A33105] Additionally, post hoc efficacy analyses showed that 32% in the galcanezumab group versus 18% in the placebo group were complete responders.[A33105] Finally, the most commonly reported adverse events associated with galcanezumab use are headache, nasopharyngitis, hematuria, dermatitis, diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112]
Mechanism of Action	Galcanezumab is a fully humanized monoclonal antibody designed and manufactured specifically against calcitonin gene-related peptide (CGRP).[A33105,L4894] It binds avidly to human CGRP, with a binding affinity (Kd) of 31 pM (4.5 ng/mL). Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy.[A33090] Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients.[A33090] For all these reasons, the binding of CGRP to interfere with its activity was specifically designed to be the mechanism of action for galcanezumab to take advantage of in reversing the migraine-inducing activity of natural CGRP. The binding of galcanezumab to natural endogenous CGRP subsequently interferes with its activities, such as its binding to CGRP receptors, for example. Studies have also shown that humanized monoclonal antibodies against CGRP have proven successful in reducing the frequency of migraine headaches in early clinical trials as a preventative therapeutic.[A33112]
Toxicity	Overdose and LD₅₀ date are not readily available.[L4894] The most common adverse effects associated with galcanezumab during clinical trials include headache, nasopharyngitis, hematuria, and contact dermatitis.[A33112] However, with the exception of hematuria which was not present in placebo treatment arms, the frequencies of these events were similar to placebo.[A33112] Additional frequently reported adverse effects in subjects receiving galcanezumab were diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112] The pharmacokinetics of galcanezumab were not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), based on a population pharmacokinetic analysis.[L4894] Body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab.[L4894] Renal and hepatic impairment are not expected to affect the pharmacokinetics of galcanezumab.[L4894] Population pharmacokinetic analysis of integrated data from the galcanezumab clinical studies revealed that creatinine clearance did not affect the pharmacokinetics of galcanezumab in patients with mild or moderate renal impairment.[L4894] Patients with severe renal impairment (creatinine clearance <30 mL/min) have not been studied.[L4894] Based on a population PK analysis, bilirubin concentration did not significantly influence the CL/F of galcanezumab.[L4894] Studies regarding the carcinogenic potential and genetic toxicology of galcanezumab have not yet been conducted.[L4894] When galcanezumab (0, 30, or 250 mg/kg) was administered to male rats by subcutaneous injection prior to and during mating, no adverse effects on fertility was observed.[L4894] The higher dose tested was associated with a plasma exposure (Cave, ss) 8 times that in humans at the recommended human dose (RHD) of 120 mg.[L4894] When galcanezumab was administered to female rats by subcutaneous injection in two studies (0, 30, or 100 mg/kg; 0 or 250 mg/kg) prior to and during mating and continuing throughout organogenesis, no adverse effects on fertility were observed.[L4894] The highest dose tested (250 mg/kg) was associated with a plasma Cave, ss 38 times that in humans at the RHD.[L4894]
Metabolism	Monoclonal antibody agents like galcanezumab are not expected to generate toxic metabolites as they generally undergo proteolysis to their constituent amino acids.[F94] In particular, after administration galcanezumab is specifically expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous immunoglobulins.[L4894] Galcanezumab is also not believed to be metabolized by liver enzymes - making drug-drug interactions relatively unlikely.[L4894]
Absorption	Following single dose subcutaneous administration, the time to maximum concentration was recorded as 5 days.[L4894] The injection site location did not appear to significantly influence the absorption of galcanezumab.[L4894] The Cmax and the area under the concentration-time curve from dosing to infinity (AUC (0-8)) are generally considered to be dose proportional over a dose range.[A33112]
	The apparent volume of distribution of galcanezumab is documented to be 7.3 L, with 34% inter-individual variability.[L4894]
Clearance	It is noted that the clearance of galcanezumab is by proteolysis.[A33112] The apparent clearance of galcanezumab was recorded as 0.008 L/h.[L4894]
Categories	Calcitonin Gene-Related Peptide (CGRP) Antagonists
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Calcitonin gene-related peptide 1,Calcitonin gene-related peptide 2
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	NA
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15464
Therapeutic ID	Th1598
Protein Name	Galcanezumab
Sequence	>Th1598_Galcanezumab QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVYIQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG
Molecular Weight	147000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The mean serum half-life of galcanezumab is similar at all dose levels at about 25-30 days.[A33112] The elimination half-life of galcanezumab was ultimately approximately 27 days.[L4894]
Description	LY2951742/galcanezumab is a fully humanized monoclonal antibody against human calcitonin gene-related peptide (CGRP) that is developed by ELi Lilly and Company.[A33105] This therapy is given as a single subcutaneous injection twice a month and ongoing clinical trials for the agent are for episodic and chronic migraine as well as cluster headaches.[A33114] Although various small-molecule CGRP receptor antagonists have also been developed, humanized monoclonal antibodies like galcanezumab are specifically designed to potently and selectively bind to the CGRP entities directly.[A33112] Given this target specificity, lack of off-target toxicity, and characteristic proteolysis profile of immunoglobulin antibodies to not undergo metabolism by liver enzymes, galcanezumab possesses favourable and promising safety and tolerability.[A33112] Galcanezumab was given FDA approval on 27 September 2018.[L4894]
Indication/Disease	Galcanezumab is a humanized monoclonal antibody that is indicated for migraine prophylaxis and treatment of episodic cluster headaches in adults by binding endogenous human calcitonin gene-related peptide (CGRP).[A33112,L4894]
Pharmacodynamics	Galcanezumab is administered as a subcutaneous injection.[A33112,A33114,L4894] During clinical trials, it was noted that galcanezumab therapy resulted in a significant reduction in the mean number of migraine headache days and a good tolerability profile.[A33105] Additionally, post hoc efficacy analyses showed that 32% in the galcanezumab group versus 18% in the placebo group were complete responders.[A33105] Finally, the most commonly reported adverse events associated with galcanezumab use are headache, nasopharyngitis, hematuria, dermatitis, diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112]
Mechanism of Action	Galcanezumab is a fully humanized monoclonal antibody designed and manufactured specifically against calcitonin gene-related peptide (CGRP).[A33105,L4894] It binds avidly to human CGRP, with a binding affinity (Kd) of 31 pM (4.5 ng/mL). Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy.[A33090] Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients.[A33090] For all these reasons, the binding of CGRP to interfere with its activity was specifically designed to be the mechanism of action for galcanezumab to take advantage of in reversing the migraine-inducing activity of natural CGRP. The binding of galcanezumab to natural endogenous CGRP subsequently interferes with its activities, such as its binding to CGRP receptors, for example. Studies have also shown that humanized monoclonal antibodies against CGRP have proven successful in reducing the frequency of migraine headaches in early clinical trials as a preventative therapeutic.[A33112]
Toxicity	Overdose and LD₅₀ date are not readily available.[L4894] The most common adverse effects associated with galcanezumab during clinical trials include headache, nasopharyngitis, hematuria, and contact dermatitis.[A33112] However, with the exception of hematuria which was not present in placebo treatment arms, the frequencies of these events were similar to placebo.[A33112] Additional frequently reported adverse effects in subjects receiving galcanezumab were diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112] The pharmacokinetics of galcanezumab were not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), based on a population pharmacokinetic analysis.[L4894] Body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab.[L4894] Renal and hepatic impairment are not expected to affect the pharmacokinetics of galcanezumab.[L4894] Population pharmacokinetic analysis of integrated data from the galcanezumab clinical studies revealed that creatinine clearance did not affect the pharmacokinetics of galcanezumab in patients with mild or moderate renal impairment.[L4894] Patients with severe renal impairment (creatinine clearance <30 mL/min) have not been studied.[L4894] Based on a population PK analysis, bilirubin concentration did not significantly influence the CL/F of galcanezumab.[L4894] Studies regarding the carcinogenic potential and genetic toxicology of galcanezumab have not yet been conducted.[L4894] When galcanezumab (0, 30, or 250 mg/kg) was administered to male rats by subcutaneous injection prior to and during mating, no adverse effects on fertility was observed.[L4894] The higher dose tested was associated with a plasma exposure (Cave, ss) 8 times that in humans at the recommended human dose (RHD) of 120 mg.[L4894] When galcanezumab was administered to female rats by subcutaneous injection in two studies (0, 30, or 100 mg/kg; 0 or 250 mg/kg) prior to and during mating and continuing throughout organogenesis, no adverse effects on fertility were observed.[L4894] The highest dose tested (250 mg/kg) was associated with a plasma Cave, ss 38 times that in humans at the RHD.[L4894]
Metabolism	Monoclonal antibody agents like galcanezumab are not expected to generate toxic metabolites as they generally undergo proteolysis to their constituent amino acids.[F94] In particular, after administration galcanezumab is specifically expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous immunoglobulins.[L4894] Galcanezumab is also not believed to be metabolized by liver enzymes - making drug-drug interactions relatively unlikely.[L4894]
Absorption	Following single dose subcutaneous administration, the time to maximum concentration was recorded as 5 days.[L4894] The injection site location did not appear to significantly influence the absorption of galcanezumab.[L4894] The Cmax and the area under the concentration-time curve from dosing to infinity (AUC (0-8)) are generally considered to be dose proportional over a dose range.[A33112]
	The apparent volume of distribution of galcanezumab is documented to be 7.3 L, with 34% inter-individual variability.[L4894]
Clearance	It is noted that the clearance of galcanezumab is by proteolysis.[A33112] The apparent clearance of galcanezumab was recorded as 0.008 L/h.[L4894]
Categories	Calcitonin Gene-Related Peptide Receptor Antagonists
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Calcitonin gene-related peptide 1,Calcitonin gene-related peptide 2
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	NA
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15465
Therapeutic ID	Th1598
Protein Name	Galcanezumab
Sequence	>Th1598_Galcanezumab QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVYIQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG
Molecular Weight	147000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The mean serum half-life of galcanezumab is similar at all dose levels at about 25-30 days.[A33112] The elimination half-life of galcanezumab was ultimately approximately 27 days.[L4894]
Description	LY2951742/galcanezumab is a fully humanized monoclonal antibody against human calcitonin gene-related peptide (CGRP) that is developed by ELi Lilly and Company.[A33105] This therapy is given as a single subcutaneous injection twice a month and ongoing clinical trials for the agent are for episodic and chronic migraine as well as cluster headaches.[A33114] Although various small-molecule CGRP receptor antagonists have also been developed, humanized monoclonal antibodies like galcanezumab are specifically designed to potently and selectively bind to the CGRP entities directly.[A33112] Given this target specificity, lack of off-target toxicity, and characteristic proteolysis profile of immunoglobulin antibodies to not undergo metabolism by liver enzymes, galcanezumab possesses favourable and promising safety and tolerability.[A33112] Galcanezumab was given FDA approval on 27 September 2018.[L4894]
Indication/Disease	Galcanezumab is a humanized monoclonal antibody that is indicated for migraine prophylaxis and treatment of episodic cluster headaches in adults by binding endogenous human calcitonin gene-related peptide (CGRP).[A33112,L4894]
Pharmacodynamics	Galcanezumab is administered as a subcutaneous injection.[A33112,A33114,L4894] During clinical trials, it was noted that galcanezumab therapy resulted in a significant reduction in the mean number of migraine headache days and a good tolerability profile.[A33105] Additionally, post hoc efficacy analyses showed that 32% in the galcanezumab group versus 18% in the placebo group were complete responders.[A33105] Finally, the most commonly reported adverse events associated with galcanezumab use are headache, nasopharyngitis, hematuria, dermatitis, diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112]
Mechanism of Action	Galcanezumab is a fully humanized monoclonal antibody designed and manufactured specifically against calcitonin gene-related peptide (CGRP).[A33105,L4894] It binds avidly to human CGRP, with a binding affinity (Kd) of 31 pM (4.5 ng/mL). Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy.[A33090] Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients.[A33090] For all these reasons, the binding of CGRP to interfere with its activity was specifically designed to be the mechanism of action for galcanezumab to take advantage of in reversing the migraine-inducing activity of natural CGRP. The binding of galcanezumab to natural endogenous CGRP subsequently interferes with its activities, such as its binding to CGRP receptors, for example. Studies have also shown that humanized monoclonal antibodies against CGRP have proven successful in reducing the frequency of migraine headaches in early clinical trials as a preventative therapeutic.[A33112]
Toxicity	Overdose and LD₅₀ date are not readily available.[L4894] The most common adverse effects associated with galcanezumab during clinical trials include headache, nasopharyngitis, hematuria, and contact dermatitis.[A33112] However, with the exception of hematuria which was not present in placebo treatment arms, the frequencies of these events were similar to placebo.[A33112] Additional frequently reported adverse effects in subjects receiving galcanezumab were diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112] The pharmacokinetics of galcanezumab were not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), based on a population pharmacokinetic analysis.[L4894] Body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab.[L4894] Renal and hepatic impairment are not expected to affect the pharmacokinetics of galcanezumab.[L4894] Population pharmacokinetic analysis of integrated data from the galcanezumab clinical studies revealed that creatinine clearance did not affect the pharmacokinetics of galcanezumab in patients with mild or moderate renal impairment.[L4894] Patients with severe renal impairment (creatinine clearance <30 mL/min) have not been studied.[L4894] Based on a population PK analysis, bilirubin concentration did not significantly influence the CL/F of galcanezumab.[L4894] Studies regarding the carcinogenic potential and genetic toxicology of galcanezumab have not yet been conducted.[L4894] When galcanezumab (0, 30, or 250 mg/kg) was administered to male rats by subcutaneous injection prior to and during mating, no adverse effects on fertility was observed.[L4894] The higher dose tested was associated with a plasma exposure (Cave, ss) 8 times that in humans at the recommended human dose (RHD) of 120 mg.[L4894] When galcanezumab was administered to female rats by subcutaneous injection in two studies (0, 30, or 100 mg/kg; 0 or 250 mg/kg) prior to and during mating and continuing throughout organogenesis, no adverse effects on fertility were observed.[L4894] The highest dose tested (250 mg/kg) was associated with a plasma Cave, ss 38 times that in humans at the RHD.[L4894]
Metabolism	Monoclonal antibody agents like galcanezumab are not expected to generate toxic metabolites as they generally undergo proteolysis to their constituent amino acids.[F94] In particular, after administration galcanezumab is specifically expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous immunoglobulins.[L4894] Galcanezumab is also not believed to be metabolized by liver enzymes - making drug-drug interactions relatively unlikely.[L4894]
Absorption	Following single dose subcutaneous administration, the time to maximum concentration was recorded as 5 days.[L4894] The injection site location did not appear to significantly influence the absorption of galcanezumab.[L4894] The Cmax and the area under the concentration-time curve from dosing to infinity (AUC (0-8)) are generally considered to be dose proportional over a dose range.[A33112]
	The apparent volume of distribution of galcanezumab is documented to be 7.3 L, with 34% inter-individual variability.[L4894]
Clearance	It is noted that the clearance of galcanezumab is by proteolysis.[A33112] The apparent clearance of galcanezumab was recorded as 0.008 L/h.[L4894]
Categories	Central Nervous System Agents
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Calcitonin gene-related peptide 1,Calcitonin gene-related peptide 2
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	NA
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15466
Therapeutic ID	Th1598
Protein Name	Galcanezumab
Sequence	>Th1598_Galcanezumab QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVYIQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG
Molecular Weight	147000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The mean serum half-life of galcanezumab is similar at all dose levels at about 25-30 days.[A33112] The elimination half-life of galcanezumab was ultimately approximately 27 days.[L4894]
Description	LY2951742/galcanezumab is a fully humanized monoclonal antibody against human calcitonin gene-related peptide (CGRP) that is developed by ELi Lilly and Company.[A33105] This therapy is given as a single subcutaneous injection twice a month and ongoing clinical trials for the agent are for episodic and chronic migraine as well as cluster headaches.[A33114] Although various small-molecule CGRP receptor antagonists have also been developed, humanized monoclonal antibodies like galcanezumab are specifically designed to potently and selectively bind to the CGRP entities directly.[A33112] Given this target specificity, lack of off-target toxicity, and characteristic proteolysis profile of immunoglobulin antibodies to not undergo metabolism by liver enzymes, galcanezumab possesses favourable and promising safety and tolerability.[A33112] Galcanezumab was given FDA approval on 27 September 2018.[L4894]
Indication/Disease	Galcanezumab is a humanized monoclonal antibody that is indicated for migraine prophylaxis and treatment of episodic cluster headaches in adults by binding endogenous human calcitonin gene-related peptide (CGRP).[A33112,L4894]
Pharmacodynamics	Galcanezumab is administered as a subcutaneous injection.[A33112,A33114,L4894] During clinical trials, it was noted that galcanezumab therapy resulted in a significant reduction in the mean number of migraine headache days and a good tolerability profile.[A33105] Additionally, post hoc efficacy analyses showed that 32% in the galcanezumab group versus 18% in the placebo group were complete responders.[A33105] Finally, the most commonly reported adverse events associated with galcanezumab use are headache, nasopharyngitis, hematuria, dermatitis, diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112]
Mechanism of Action	Galcanezumab is a fully humanized monoclonal antibody designed and manufactured specifically against calcitonin gene-related peptide (CGRP).[A33105,L4894] It binds avidly to human CGRP, with a binding affinity (Kd) of 31 pM (4.5 ng/mL). Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy.[A33090] Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients.[A33090] For all these reasons, the binding of CGRP to interfere with its activity was specifically designed to be the mechanism of action for galcanezumab to take advantage of in reversing the migraine-inducing activity of natural CGRP. The binding of galcanezumab to natural endogenous CGRP subsequently interferes with its activities, such as its binding to CGRP receptors, for example. Studies have also shown that humanized monoclonal antibodies against CGRP have proven successful in reducing the frequency of migraine headaches in early clinical trials as a preventative therapeutic.[A33112]
Toxicity	Overdose and LD₅₀ date are not readily available.[L4894] The most common adverse effects associated with galcanezumab during clinical trials include headache, nasopharyngitis, hematuria, and contact dermatitis.[A33112] However, with the exception of hematuria which was not present in placebo treatment arms, the frequencies of these events were similar to placebo.[A33112] Additional frequently reported adverse effects in subjects receiving galcanezumab were diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112] The pharmacokinetics of galcanezumab were not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), based on a population pharmacokinetic analysis.[L4894] Body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab.[L4894] Renal and hepatic impairment are not expected to affect the pharmacokinetics of galcanezumab.[L4894] Population pharmacokinetic analysis of integrated data from the galcanezumab clinical studies revealed that creatinine clearance did not affect the pharmacokinetics of galcanezumab in patients with mild or moderate renal impairment.[L4894] Patients with severe renal impairment (creatinine clearance <30 mL/min) have not been studied.[L4894] Based on a population PK analysis, bilirubin concentration did not significantly influence the CL/F of galcanezumab.[L4894] Studies regarding the carcinogenic potential and genetic toxicology of galcanezumab have not yet been conducted.[L4894] When galcanezumab (0, 30, or 250 mg/kg) was administered to male rats by subcutaneous injection prior to and during mating, no adverse effects on fertility was observed.[L4894] The higher dose tested was associated with a plasma exposure (Cave, ss) 8 times that in humans at the recommended human dose (RHD) of 120 mg.[L4894] When galcanezumab was administered to female rats by subcutaneous injection in two studies (0, 30, or 100 mg/kg; 0 or 250 mg/kg) prior to and during mating and continuing throughout organogenesis, no adverse effects on fertility were observed.[L4894] The highest dose tested (250 mg/kg) was associated with a plasma Cave, ss 38 times that in humans at the RHD.[L4894]
Metabolism	Monoclonal antibody agents like galcanezumab are not expected to generate toxic metabolites as they generally undergo proteolysis to their constituent amino acids.[F94] In particular, after administration galcanezumab is specifically expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous immunoglobulins.[L4894] Galcanezumab is also not believed to be metabolized by liver enzymes - making drug-drug interactions relatively unlikely.[L4894]
Absorption	Following single dose subcutaneous administration, the time to maximum concentration was recorded as 5 days.[L4894] The injection site location did not appear to significantly influence the absorption of galcanezumab.[L4894] The Cmax and the area under the concentration-time curve from dosing to infinity (AUC (0-8)) are generally considered to be dose proportional over a dose range.[A33112]
	The apparent volume of distribution of galcanezumab is documented to be 7.3 L, with 34% inter-individual variability.[L4894]
Clearance	It is noted that the clearance of galcanezumab is by proteolysis.[A33112] The apparent clearance of galcanezumab was recorded as 0.008 L/h.[L4894]
Categories	Globulins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Calcitonin gene-related peptide 1,Calcitonin gene-related peptide 2
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	NA
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15467
Therapeutic ID	Th1598
Protein Name	Galcanezumab
Sequence	>Th1598_Galcanezumab QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVYIQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG
Molecular Weight	147000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The mean serum half-life of galcanezumab is similar at all dose levels at about 25-30 days.[A33112] The elimination half-life of galcanezumab was ultimately approximately 27 days.[L4894]
Description	LY2951742/galcanezumab is a fully humanized monoclonal antibody against human calcitonin gene-related peptide (CGRP) that is developed by ELi Lilly and Company.[A33105] This therapy is given as a single subcutaneous injection twice a month and ongoing clinical trials for the agent are for episodic and chronic migraine as well as cluster headaches.[A33114] Although various small-molecule CGRP receptor antagonists have also been developed, humanized monoclonal antibodies like galcanezumab are specifically designed to potently and selectively bind to the CGRP entities directly.[A33112] Given this target specificity, lack of off-target toxicity, and characteristic proteolysis profile of immunoglobulin antibodies to not undergo metabolism by liver enzymes, galcanezumab possesses favourable and promising safety and tolerability.[A33112] Galcanezumab was given FDA approval on 27 September 2018.[L4894]
Indication/Disease	Galcanezumab is a humanized monoclonal antibody that is indicated for migraine prophylaxis and treatment of episodic cluster headaches in adults by binding endogenous human calcitonin gene-related peptide (CGRP).[A33112,L4894]
Pharmacodynamics	Galcanezumab is administered as a subcutaneous injection.[A33112,A33114,L4894] During clinical trials, it was noted that galcanezumab therapy resulted in a significant reduction in the mean number of migraine headache days and a good tolerability profile.[A33105] Additionally, post hoc efficacy analyses showed that 32% in the galcanezumab group versus 18% in the placebo group were complete responders.[A33105] Finally, the most commonly reported adverse events associated with galcanezumab use are headache, nasopharyngitis, hematuria, dermatitis, diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112]
Mechanism of Action	Galcanezumab is a fully humanized monoclonal antibody designed and manufactured specifically against calcitonin gene-related peptide (CGRP).[A33105,L4894] It binds avidly to human CGRP, with a binding affinity (Kd) of 31 pM (4.5 ng/mL). Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy.[A33090] Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients.[A33090] For all these reasons, the binding of CGRP to interfere with its activity was specifically designed to be the mechanism of action for galcanezumab to take advantage of in reversing the migraine-inducing activity of natural CGRP. The binding of galcanezumab to natural endogenous CGRP subsequently interferes with its activities, such as its binding to CGRP receptors, for example. Studies have also shown that humanized monoclonal antibodies against CGRP have proven successful in reducing the frequency of migraine headaches in early clinical trials as a preventative therapeutic.[A33112]
Toxicity	Overdose and LD₅₀ date are not readily available.[L4894] The most common adverse effects associated with galcanezumab during clinical trials include headache, nasopharyngitis, hematuria, and contact dermatitis.[A33112] However, with the exception of hematuria which was not present in placebo treatment arms, the frequencies of these events were similar to placebo.[A33112] Additional frequently reported adverse effects in subjects receiving galcanezumab were diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112] The pharmacokinetics of galcanezumab were not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), based on a population pharmacokinetic analysis.[L4894] Body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab.[L4894] Renal and hepatic impairment are not expected to affect the pharmacokinetics of galcanezumab.[L4894] Population pharmacokinetic analysis of integrated data from the galcanezumab clinical studies revealed that creatinine clearance did not affect the pharmacokinetics of galcanezumab in patients with mild or moderate renal impairment.[L4894] Patients with severe renal impairment (creatinine clearance <30 mL/min) have not been studied.[L4894] Based on a population PK analysis, bilirubin concentration did not significantly influence the CL/F of galcanezumab.[L4894] Studies regarding the carcinogenic potential and genetic toxicology of galcanezumab have not yet been conducted.[L4894] When galcanezumab (0, 30, or 250 mg/kg) was administered to male rats by subcutaneous injection prior to and during mating, no adverse effects on fertility was observed.[L4894] The higher dose tested was associated with a plasma exposure (Cave, ss) 8 times that in humans at the recommended human dose (RHD) of 120 mg.[L4894] When galcanezumab was administered to female rats by subcutaneous injection in two studies (0, 30, or 100 mg/kg; 0 or 250 mg/kg) prior to and during mating and continuing throughout organogenesis, no adverse effects on fertility were observed.[L4894] The highest dose tested (250 mg/kg) was associated with a plasma Cave, ss 38 times that in humans at the RHD.[L4894]
Metabolism	Monoclonal antibody agents like galcanezumab are not expected to generate toxic metabolites as they generally undergo proteolysis to their constituent amino acids.[F94] In particular, after administration galcanezumab is specifically expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous immunoglobulins.[L4894] Galcanezumab is also not believed to be metabolized by liver enzymes - making drug-drug interactions relatively unlikely.[L4894]
Absorption	Following single dose subcutaneous administration, the time to maximum concentration was recorded as 5 days.[L4894] The injection site location did not appear to significantly influence the absorption of galcanezumab.[L4894] The Cmax and the area under the concentration-time curve from dosing to infinity (AUC (0-8)) are generally considered to be dose proportional over a dose range.[A33112]
	The apparent volume of distribution of galcanezumab is documented to be 7.3 L, with 34% inter-individual variability.[L4894]
Clearance	It is noted that the clearance of galcanezumab is by proteolysis.[A33112] The apparent clearance of galcanezumab was recorded as 0.008 L/h.[L4894]
Categories	Immunoglobulins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Calcitonin gene-related peptide 1,Calcitonin gene-related peptide 2
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	NA
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15468
Therapeutic ID	Th1598
Protein Name	Galcanezumab
Sequence	>Th1598_Galcanezumab QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVYIQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG
Molecular Weight	147000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The mean serum half-life of galcanezumab is similar at all dose levels at about 25-30 days.[A33112] The elimination half-life of galcanezumab was ultimately approximately 27 days.[L4894]
Description	LY2951742/galcanezumab is a fully humanized monoclonal antibody against human calcitonin gene-related peptide (CGRP) that is developed by ELi Lilly and Company.[A33105] This therapy is given as a single subcutaneous injection twice a month and ongoing clinical trials for the agent are for episodic and chronic migraine as well as cluster headaches.[A33114] Although various small-molecule CGRP receptor antagonists have also been developed, humanized monoclonal antibodies like galcanezumab are specifically designed to potently and selectively bind to the CGRP entities directly.[A33112] Given this target specificity, lack of off-target toxicity, and characteristic proteolysis profile of immunoglobulin antibodies to not undergo metabolism by liver enzymes, galcanezumab possesses favourable and promising safety and tolerability.[A33112] Galcanezumab was given FDA approval on 27 September 2018.[L4894]
Indication/Disease	Galcanezumab is a humanized monoclonal antibody that is indicated for migraine prophylaxis and treatment of episodic cluster headaches in adults by binding endogenous human calcitonin gene-related peptide (CGRP).[A33112,L4894]
Pharmacodynamics	Galcanezumab is administered as a subcutaneous injection.[A33112,A33114,L4894] During clinical trials, it was noted that galcanezumab therapy resulted in a significant reduction in the mean number of migraine headache days and a good tolerability profile.[A33105] Additionally, post hoc efficacy analyses showed that 32% in the galcanezumab group versus 18% in the placebo group were complete responders.[A33105] Finally, the most commonly reported adverse events associated with galcanezumab use are headache, nasopharyngitis, hematuria, dermatitis, diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112]
Mechanism of Action	Galcanezumab is a fully humanized monoclonal antibody designed and manufactured specifically against calcitonin gene-related peptide (CGRP).[A33105,L4894] It binds avidly to human CGRP, with a binding affinity (Kd) of 31 pM (4.5 ng/mL). Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy.[A33090] Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients.[A33090] For all these reasons, the binding of CGRP to interfere with its activity was specifically designed to be the mechanism of action for galcanezumab to take advantage of in reversing the migraine-inducing activity of natural CGRP. The binding of galcanezumab to natural endogenous CGRP subsequently interferes with its activities, such as its binding to CGRP receptors, for example. Studies have also shown that humanized monoclonal antibodies against CGRP have proven successful in reducing the frequency of migraine headaches in early clinical trials as a preventative therapeutic.[A33112]
Toxicity	Overdose and LD₅₀ date are not readily available.[L4894] The most common adverse effects associated with galcanezumab during clinical trials include headache, nasopharyngitis, hematuria, and contact dermatitis.[A33112] However, with the exception of hematuria which was not present in placebo treatment arms, the frequencies of these events were similar to placebo.[A33112] Additional frequently reported adverse effects in subjects receiving galcanezumab were diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112] The pharmacokinetics of galcanezumab were not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), based on a population pharmacokinetic analysis.[L4894] Body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab.[L4894] Renal and hepatic impairment are not expected to affect the pharmacokinetics of galcanezumab.[L4894] Population pharmacokinetic analysis of integrated data from the galcanezumab clinical studies revealed that creatinine clearance did not affect the pharmacokinetics of galcanezumab in patients with mild or moderate renal impairment.[L4894] Patients with severe renal impairment (creatinine clearance <30 mL/min) have not been studied.[L4894] Based on a population PK analysis, bilirubin concentration did not significantly influence the CL/F of galcanezumab.[L4894] Studies regarding the carcinogenic potential and genetic toxicology of galcanezumab have not yet been conducted.[L4894] When galcanezumab (0, 30, or 250 mg/kg) was administered to male rats by subcutaneous injection prior to and during mating, no adverse effects on fertility was observed.[L4894] The higher dose tested was associated with a plasma exposure (Cave, ss) 8 times that in humans at the recommended human dose (RHD) of 120 mg.[L4894] When galcanezumab was administered to female rats by subcutaneous injection in two studies (0, 30, or 100 mg/kg; 0 or 250 mg/kg) prior to and during mating and continuing throughout organogenesis, no adverse effects on fertility were observed.[L4894] The highest dose tested (250 mg/kg) was associated with a plasma Cave, ss 38 times that in humans at the RHD.[L4894]
Metabolism	Monoclonal antibody agents like galcanezumab are not expected to generate toxic metabolites as they generally undergo proteolysis to their constituent amino acids.[F94] In particular, after administration galcanezumab is specifically expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous immunoglobulins.[L4894] Galcanezumab is also not believed to be metabolized by liver enzymes - making drug-drug interactions relatively unlikely.[L4894]
Absorption	Following single dose subcutaneous administration, the time to maximum concentration was recorded as 5 days.[L4894] The injection site location did not appear to significantly influence the absorption of galcanezumab.[L4894] The Cmax and the area under the concentration-time curve from dosing to infinity (AUC (0-8)) are generally considered to be dose proportional over a dose range.[A33112]
	The apparent volume of distribution of galcanezumab is documented to be 7.3 L, with 34% inter-individual variability.[L4894]
Clearance	It is noted that the clearance of galcanezumab is by proteolysis.[A33112] The apparent clearance of galcanezumab was recorded as 0.008 L/h.[L4894]
Categories	Immunoproteins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Calcitonin gene-related peptide 1,Calcitonin gene-related peptide 2
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	NA
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15469
Therapeutic ID	Th1598
Protein Name	Galcanezumab
Sequence	>Th1598_Galcanezumab QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVYIQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG
Molecular Weight	147000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The mean serum half-life of galcanezumab is similar at all dose levels at about 25-30 days.[A33112] The elimination half-life of galcanezumab was ultimately approximately 27 days.[L4894]
Description	LY2951742/galcanezumab is a fully humanized monoclonal antibody against human calcitonin gene-related peptide (CGRP) that is developed by ELi Lilly and Company.[A33105] This therapy is given as a single subcutaneous injection twice a month and ongoing clinical trials for the agent are for episodic and chronic migraine as well as cluster headaches.[A33114] Although various small-molecule CGRP receptor antagonists have also been developed, humanized monoclonal antibodies like galcanezumab are specifically designed to potently and selectively bind to the CGRP entities directly.[A33112] Given this target specificity, lack of off-target toxicity, and characteristic proteolysis profile of immunoglobulin antibodies to not undergo metabolism by liver enzymes, galcanezumab possesses favourable and promising safety and tolerability.[A33112] Galcanezumab was given FDA approval on 27 September 2018.[L4894]
Indication/Disease	Galcanezumab is a humanized monoclonal antibody that is indicated for migraine prophylaxis and treatment of episodic cluster headaches in adults by binding endogenous human calcitonin gene-related peptide (CGRP).[A33112,L4894]
Pharmacodynamics	Galcanezumab is administered as a subcutaneous injection.[A33112,A33114,L4894] During clinical trials, it was noted that galcanezumab therapy resulted in a significant reduction in the mean number of migraine headache days and a good tolerability profile.[A33105] Additionally, post hoc efficacy analyses showed that 32% in the galcanezumab group versus 18% in the placebo group were complete responders.[A33105] Finally, the most commonly reported adverse events associated with galcanezumab use are headache, nasopharyngitis, hematuria, dermatitis, diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112]
Mechanism of Action	Galcanezumab is a fully humanized monoclonal antibody designed and manufactured specifically against calcitonin gene-related peptide (CGRP).[A33105,L4894] It binds avidly to human CGRP, with a binding affinity (Kd) of 31 pM (4.5 ng/mL). Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy.[A33090] Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients.[A33090] For all these reasons, the binding of CGRP to interfere with its activity was specifically designed to be the mechanism of action for galcanezumab to take advantage of in reversing the migraine-inducing activity of natural CGRP. The binding of galcanezumab to natural endogenous CGRP subsequently interferes with its activities, such as its binding to CGRP receptors, for example. Studies have also shown that humanized monoclonal antibodies against CGRP have proven successful in reducing the frequency of migraine headaches in early clinical trials as a preventative therapeutic.[A33112]
Toxicity	Overdose and LD₅₀ date are not readily available.[L4894] The most common adverse effects associated with galcanezumab during clinical trials include headache, nasopharyngitis, hematuria, and contact dermatitis.[A33112] However, with the exception of hematuria which was not present in placebo treatment arms, the frequencies of these events were similar to placebo.[A33112] Additional frequently reported adverse effects in subjects receiving galcanezumab were diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112] The pharmacokinetics of galcanezumab were not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), based on a population pharmacokinetic analysis.[L4894] Body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab.[L4894] Renal and hepatic impairment are not expected to affect the pharmacokinetics of galcanezumab.[L4894] Population pharmacokinetic analysis of integrated data from the galcanezumab clinical studies revealed that creatinine clearance did not affect the pharmacokinetics of galcanezumab in patients with mild or moderate renal impairment.[L4894] Patients with severe renal impairment (creatinine clearance <30 mL/min) have not been studied.[L4894] Based on a population PK analysis, bilirubin concentration did not significantly influence the CL/F of galcanezumab.[L4894] Studies regarding the carcinogenic potential and genetic toxicology of galcanezumab have not yet been conducted.[L4894] When galcanezumab (0, 30, or 250 mg/kg) was administered to male rats by subcutaneous injection prior to and during mating, no adverse effects on fertility was observed.[L4894] The higher dose tested was associated with a plasma exposure (Cave, ss) 8 times that in humans at the recommended human dose (RHD) of 120 mg.[L4894] When galcanezumab was administered to female rats by subcutaneous injection in two studies (0, 30, or 100 mg/kg; 0 or 250 mg/kg) prior to and during mating and continuing throughout organogenesis, no adverse effects on fertility were observed.[L4894] The highest dose tested (250 mg/kg) was associated with a plasma Cave, ss 38 times that in humans at the RHD.[L4894]
Metabolism	Monoclonal antibody agents like galcanezumab are not expected to generate toxic metabolites as they generally undergo proteolysis to their constituent amino acids.[F94] In particular, after administration galcanezumab is specifically expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous immunoglobulins.[L4894] Galcanezumab is also not believed to be metabolized by liver enzymes - making drug-drug interactions relatively unlikely.[L4894]
Absorption	Following single dose subcutaneous administration, the time to maximum concentration was recorded as 5 days.[L4894] The injection site location did not appear to significantly influence the absorption of galcanezumab.[L4894] The Cmax and the area under the concentration-time curve from dosing to infinity (AUC (0-8)) are generally considered to be dose proportional over a dose range.[A33112]
	The apparent volume of distribution of galcanezumab is documented to be 7.3 L, with 34% inter-individual variability.[L4894]
Clearance	It is noted that the clearance of galcanezumab is by proteolysis.[A33112] The apparent clearance of galcanezumab was recorded as 0.008 L/h.[L4894]
Categories	Nervous System
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Calcitonin gene-related peptide 1,Calcitonin gene-related peptide 2
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	NA
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15470
Therapeutic ID	Th1598
Protein Name	Galcanezumab
Sequence	>Th1598_Galcanezumab QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVYIQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG
Molecular Weight	147000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The mean serum half-life of galcanezumab is similar at all dose levels at about 25-30 days.[A33112] The elimination half-life of galcanezumab was ultimately approximately 27 days.[L4894]
Description	LY2951742/galcanezumab is a fully humanized monoclonal antibody against human calcitonin gene-related peptide (CGRP) that is developed by ELi Lilly and Company.[A33105] This therapy is given as a single subcutaneous injection twice a month and ongoing clinical trials for the agent are for episodic and chronic migraine as well as cluster headaches.[A33114] Although various small-molecule CGRP receptor antagonists have also been developed, humanized monoclonal antibodies like galcanezumab are specifically designed to potently and selectively bind to the CGRP entities directly.[A33112] Given this target specificity, lack of off-target toxicity, and characteristic proteolysis profile of immunoglobulin antibodies to not undergo metabolism by liver enzymes, galcanezumab possesses favourable and promising safety and tolerability.[A33112] Galcanezumab was given FDA approval on 27 September 2018.[L4894]
Indication/Disease	Galcanezumab is a humanized monoclonal antibody that is indicated for migraine prophylaxis and treatment of episodic cluster headaches in adults by binding endogenous human calcitonin gene-related peptide (CGRP).[A33112,L4894]
Pharmacodynamics	Galcanezumab is administered as a subcutaneous injection.[A33112,A33114,L4894] During clinical trials, it was noted that galcanezumab therapy resulted in a significant reduction in the mean number of migraine headache days and a good tolerability profile.[A33105] Additionally, post hoc efficacy analyses showed that 32% in the galcanezumab group versus 18% in the placebo group were complete responders.[A33105] Finally, the most commonly reported adverse events associated with galcanezumab use are headache, nasopharyngitis, hematuria, dermatitis, diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112]
Mechanism of Action	Galcanezumab is a fully humanized monoclonal antibody designed and manufactured specifically against calcitonin gene-related peptide (CGRP).[A33105,L4894] It binds avidly to human CGRP, with a binding affinity (Kd) of 31 pM (4.5 ng/mL). Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy.[A33090] Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients.[A33090] For all these reasons, the binding of CGRP to interfere with its activity was specifically designed to be the mechanism of action for galcanezumab to take advantage of in reversing the migraine-inducing activity of natural CGRP. The binding of galcanezumab to natural endogenous CGRP subsequently interferes with its activities, such as its binding to CGRP receptors, for example. Studies have also shown that humanized monoclonal antibodies against CGRP have proven successful in reducing the frequency of migraine headaches in early clinical trials as a preventative therapeutic.[A33112]
Toxicity	Overdose and LD₅₀ date are not readily available.[L4894] The most common adverse effects associated with galcanezumab during clinical trials include headache, nasopharyngitis, hematuria, and contact dermatitis.[A33112] However, with the exception of hematuria which was not present in placebo treatment arms, the frequencies of these events were similar to placebo.[A33112] Additional frequently reported adverse effects in subjects receiving galcanezumab were diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112] The pharmacokinetics of galcanezumab were not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), based on a population pharmacokinetic analysis.[L4894] Body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab.[L4894] Renal and hepatic impairment are not expected to affect the pharmacokinetics of galcanezumab.[L4894] Population pharmacokinetic analysis of integrated data from the galcanezumab clinical studies revealed that creatinine clearance did not affect the pharmacokinetics of galcanezumab in patients with mild or moderate renal impairment.[L4894] Patients with severe renal impairment (creatinine clearance <30 mL/min) have not been studied.[L4894] Based on a population PK analysis, bilirubin concentration did not significantly influence the CL/F of galcanezumab.[L4894] Studies regarding the carcinogenic potential and genetic toxicology of galcanezumab have not yet been conducted.[L4894] When galcanezumab (0, 30, or 250 mg/kg) was administered to male rats by subcutaneous injection prior to and during mating, no adverse effects on fertility was observed.[L4894] The higher dose tested was associated with a plasma exposure (Cave, ss) 8 times that in humans at the recommended human dose (RHD) of 120 mg.[L4894] When galcanezumab was administered to female rats by subcutaneous injection in two studies (0, 30, or 100 mg/kg; 0 or 250 mg/kg) prior to and during mating and continuing throughout organogenesis, no adverse effects on fertility were observed.[L4894] The highest dose tested (250 mg/kg) was associated with a plasma Cave, ss 38 times that in humans at the RHD.[L4894]
Metabolism	Monoclonal antibody agents like galcanezumab are not expected to generate toxic metabolites as they generally undergo proteolysis to their constituent amino acids.[F94] In particular, after administration galcanezumab is specifically expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous immunoglobulins.[L4894] Galcanezumab is also not believed to be metabolized by liver enzymes - making drug-drug interactions relatively unlikely.[L4894]
Absorption	Following single dose subcutaneous administration, the time to maximum concentration was recorded as 5 days.[L4894] The injection site location did not appear to significantly influence the absorption of galcanezumab.[L4894] The Cmax and the area under the concentration-time curve from dosing to infinity (AUC (0-8)) are generally considered to be dose proportional over a dose range.[A33112]
	The apparent volume of distribution of galcanezumab is documented to be 7.3 L, with 34% inter-individual variability.[L4894]
Clearance	It is noted that the clearance of galcanezumab is by proteolysis.[A33112] The apparent clearance of galcanezumab was recorded as 0.008 L/h.[L4894]
Categories	Peripheral Nervous System Agents
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Calcitonin gene-related peptide 1,Calcitonin gene-related peptide 2
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	NA
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15471
Therapeutic ID	Th1598
Protein Name	Galcanezumab
Sequence	>Th1598_Galcanezumab QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVYIQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG
Molecular Weight	147000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The mean serum half-life of galcanezumab is similar at all dose levels at about 25-30 days.[A33112] The elimination half-life of galcanezumab was ultimately approximately 27 days.[L4894]
Description	LY2951742/galcanezumab is a fully humanized monoclonal antibody against human calcitonin gene-related peptide (CGRP) that is developed by ELi Lilly and Company.[A33105] This therapy is given as a single subcutaneous injection twice a month and ongoing clinical trials for the agent are for episodic and chronic migraine as well as cluster headaches.[A33114] Although various small-molecule CGRP receptor antagonists have also been developed, humanized monoclonal antibodies like galcanezumab are specifically designed to potently and selectively bind to the CGRP entities directly.[A33112] Given this target specificity, lack of off-target toxicity, and characteristic proteolysis profile of immunoglobulin antibodies to not undergo metabolism by liver enzymes, galcanezumab possesses favourable and promising safety and tolerability.[A33112] Galcanezumab was given FDA approval on 27 September 2018.[L4894]
Indication/Disease	Galcanezumab is a humanized monoclonal antibody that is indicated for migraine prophylaxis and treatment of episodic cluster headaches in adults by binding endogenous human calcitonin gene-related peptide (CGRP).[A33112,L4894]
Pharmacodynamics	Galcanezumab is administered as a subcutaneous injection.[A33112,A33114,L4894] During clinical trials, it was noted that galcanezumab therapy resulted in a significant reduction in the mean number of migraine headache days and a good tolerability profile.[A33105] Additionally, post hoc efficacy analyses showed that 32% in the galcanezumab group versus 18% in the placebo group were complete responders.[A33105] Finally, the most commonly reported adverse events associated with galcanezumab use are headache, nasopharyngitis, hematuria, dermatitis, diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112]
Mechanism of Action	Galcanezumab is a fully humanized monoclonal antibody designed and manufactured specifically against calcitonin gene-related peptide (CGRP).[A33105,L4894] It binds avidly to human CGRP, with a binding affinity (Kd) of 31 pM (4.5 ng/mL). Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy.[A33090] Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients.[A33090] For all these reasons, the binding of CGRP to interfere with its activity was specifically designed to be the mechanism of action for galcanezumab to take advantage of in reversing the migraine-inducing activity of natural CGRP. The binding of galcanezumab to natural endogenous CGRP subsequently interferes with its activities, such as its binding to CGRP receptors, for example. Studies have also shown that humanized monoclonal antibodies against CGRP have proven successful in reducing the frequency of migraine headaches in early clinical trials as a preventative therapeutic.[A33112]
Toxicity	Overdose and LD₅₀ date are not readily available.[L4894] The most common adverse effects associated with galcanezumab during clinical trials include headache, nasopharyngitis, hematuria, and contact dermatitis.[A33112] However, with the exception of hematuria which was not present in placebo treatment arms, the frequencies of these events were similar to placebo.[A33112] Additional frequently reported adverse effects in subjects receiving galcanezumab were diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112] The pharmacokinetics of galcanezumab were not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), based on a population pharmacokinetic analysis.[L4894] Body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab.[L4894] Renal and hepatic impairment are not expected to affect the pharmacokinetics of galcanezumab.[L4894] Population pharmacokinetic analysis of integrated data from the galcanezumab clinical studies revealed that creatinine clearance did not affect the pharmacokinetics of galcanezumab in patients with mild or moderate renal impairment.[L4894] Patients with severe renal impairment (creatinine clearance <30 mL/min) have not been studied.[L4894] Based on a population PK analysis, bilirubin concentration did not significantly influence the CL/F of galcanezumab.[L4894] Studies regarding the carcinogenic potential and genetic toxicology of galcanezumab have not yet been conducted.[L4894] When galcanezumab (0, 30, or 250 mg/kg) was administered to male rats by subcutaneous injection prior to and during mating, no adverse effects on fertility was observed.[L4894] The higher dose tested was associated with a plasma exposure (Cave, ss) 8 times that in humans at the recommended human dose (RHD) of 120 mg.[L4894] When galcanezumab was administered to female rats by subcutaneous injection in two studies (0, 30, or 100 mg/kg; 0 or 250 mg/kg) prior to and during mating and continuing throughout organogenesis, no adverse effects on fertility were observed.[L4894] The highest dose tested (250 mg/kg) was associated with a plasma Cave, ss 38 times that in humans at the RHD.[L4894]
Metabolism	Monoclonal antibody agents like galcanezumab are not expected to generate toxic metabolites as they generally undergo proteolysis to their constituent amino acids.[F94] In particular, after administration galcanezumab is specifically expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous immunoglobulins.[L4894] Galcanezumab is also not believed to be metabolized by liver enzymes - making drug-drug interactions relatively unlikely.[L4894]
Absorption	Following single dose subcutaneous administration, the time to maximum concentration was recorded as 5 days.[L4894] The injection site location did not appear to significantly influence the absorption of galcanezumab.[L4894] The Cmax and the area under the concentration-time curve from dosing to infinity (AUC (0-8)) are generally considered to be dose proportional over a dose range.[A33112]
	The apparent volume of distribution of galcanezumab is documented to be 7.3 L, with 34% inter-individual variability.[L4894]
Clearance	It is noted that the clearance of galcanezumab is by proteolysis.[A33112] The apparent clearance of galcanezumab was recorded as 0.008 L/h.[L4894]
Categories	Proteins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Calcitonin gene-related peptide 1,Calcitonin gene-related peptide 2
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	NA
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15472
Therapeutic ID	Th1598
Protein Name	Galcanezumab
Sequence	>Th1598_Galcanezumab QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVYIQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG
Molecular Weight	147000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The mean serum half-life of galcanezumab is similar at all dose levels at about 25-30 days.[A33112] The elimination half-life of galcanezumab was ultimately approximately 27 days.[L4894]
Description	LY2951742/galcanezumab is a fully humanized monoclonal antibody against human calcitonin gene-related peptide (CGRP) that is developed by ELi Lilly and Company.[A33105] This therapy is given as a single subcutaneous injection twice a month and ongoing clinical trials for the agent are for episodic and chronic migraine as well as cluster headaches.[A33114] Although various small-molecule CGRP receptor antagonists have also been developed, humanized monoclonal antibodies like galcanezumab are specifically designed to potently and selectively bind to the CGRP entities directly.[A33112] Given this target specificity, lack of off-target toxicity, and characteristic proteolysis profile of immunoglobulin antibodies to not undergo metabolism by liver enzymes, galcanezumab possesses favourable and promising safety and tolerability.[A33112] Galcanezumab was given FDA approval on 27 September 2018.[L4894]
Indication/Disease	Galcanezumab is a humanized monoclonal antibody that is indicated for migraine prophylaxis and treatment of episodic cluster headaches in adults by binding endogenous human calcitonin gene-related peptide (CGRP).[A33112,L4894]
Pharmacodynamics	Galcanezumab is administered as a subcutaneous injection.[A33112,A33114,L4894] During clinical trials, it was noted that galcanezumab therapy resulted in a significant reduction in the mean number of migraine headache days and a good tolerability profile.[A33105] Additionally, post hoc efficacy analyses showed that 32% in the galcanezumab group versus 18% in the placebo group were complete responders.[A33105] Finally, the most commonly reported adverse events associated with galcanezumab use are headache, nasopharyngitis, hematuria, dermatitis, diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112]
Mechanism of Action	Galcanezumab is a fully humanized monoclonal antibody designed and manufactured specifically against calcitonin gene-related peptide (CGRP).[A33105,L4894] It binds avidly to human CGRP, with a binding affinity (Kd) of 31 pM (4.5 ng/mL). Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy.[A33090] Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients.[A33090] For all these reasons, the binding of CGRP to interfere with its activity was specifically designed to be the mechanism of action for galcanezumab to take advantage of in reversing the migraine-inducing activity of natural CGRP. The binding of galcanezumab to natural endogenous CGRP subsequently interferes with its activities, such as its binding to CGRP receptors, for example. Studies have also shown that humanized monoclonal antibodies against CGRP have proven successful in reducing the frequency of migraine headaches in early clinical trials as a preventative therapeutic.[A33112]
Toxicity	Overdose and LD₅₀ date are not readily available.[L4894] The most common adverse effects associated with galcanezumab during clinical trials include headache, nasopharyngitis, hematuria, and contact dermatitis.[A33112] However, with the exception of hematuria which was not present in placebo treatment arms, the frequencies of these events were similar to placebo.[A33112] Additional frequently reported adverse effects in subjects receiving galcanezumab were diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112] The pharmacokinetics of galcanezumab were not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), based on a population pharmacokinetic analysis.[L4894] Body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab.[L4894] Renal and hepatic impairment are not expected to affect the pharmacokinetics of galcanezumab.[L4894] Population pharmacokinetic analysis of integrated data from the galcanezumab clinical studies revealed that creatinine clearance did not affect the pharmacokinetics of galcanezumab in patients with mild or moderate renal impairment.[L4894] Patients with severe renal impairment (creatinine clearance <30 mL/min) have not been studied.[L4894] Based on a population PK analysis, bilirubin concentration did not significantly influence the CL/F of galcanezumab.[L4894] Studies regarding the carcinogenic potential and genetic toxicology of galcanezumab have not yet been conducted.[L4894] When galcanezumab (0, 30, or 250 mg/kg) was administered to male rats by subcutaneous injection prior to and during mating, no adverse effects on fertility was observed.[L4894] The higher dose tested was associated with a plasma exposure (Cave, ss) 8 times that in humans at the recommended human dose (RHD) of 120 mg.[L4894] When galcanezumab was administered to female rats by subcutaneous injection in two studies (0, 30, or 100 mg/kg; 0 or 250 mg/kg) prior to and during mating and continuing throughout organogenesis, no adverse effects on fertility were observed.[L4894] The highest dose tested (250 mg/kg) was associated with a plasma Cave, ss 38 times that in humans at the RHD.[L4894]
Metabolism	Monoclonal antibody agents like galcanezumab are not expected to generate toxic metabolites as they generally undergo proteolysis to their constituent amino acids.[F94] In particular, after administration galcanezumab is specifically expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous immunoglobulins.[L4894] Galcanezumab is also not believed to be metabolized by liver enzymes - making drug-drug interactions relatively unlikely.[L4894]
Absorption	Following single dose subcutaneous administration, the time to maximum concentration was recorded as 5 days.[L4894] The injection site location did not appear to significantly influence the absorption of galcanezumab.[L4894] The Cmax and the area under the concentration-time curve from dosing to infinity (AUC (0-8)) are generally considered to be dose proportional over a dose range.[A33112]
	The apparent volume of distribution of galcanezumab is documented to be 7.3 L, with 34% inter-individual variability.[L4894]
Clearance	It is noted that the clearance of galcanezumab is by proteolysis.[A33112] The apparent clearance of galcanezumab was recorded as 0.008 L/h.[L4894]
Categories	Sensory System Agents
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Calcitonin gene-related peptide 1,Calcitonin gene-related peptide 2
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	NA
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15473
Therapeutic ID	Th1598
Protein Name	Galcanezumab
Sequence	>Th1598_Galcanezumab QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVYIQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG
Molecular Weight	147000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The mean serum half-life of galcanezumab is similar at all dose levels at about 25-30 days.[A33112] The elimination half-life of galcanezumab was ultimately approximately 27 days.[L4894]
Description	LY2951742/galcanezumab is a fully humanized monoclonal antibody against human calcitonin gene-related peptide (CGRP) that is developed by ELi Lilly and Company.[A33105] This therapy is given as a single subcutaneous injection twice a month and ongoing clinical trials for the agent are for episodic and chronic migraine as well as cluster headaches.[A33114] Although various small-molecule CGRP receptor antagonists have also been developed, humanized monoclonal antibodies like galcanezumab are specifically designed to potently and selectively bind to the CGRP entities directly.[A33112] Given this target specificity, lack of off-target toxicity, and characteristic proteolysis profile of immunoglobulin antibodies to not undergo metabolism by liver enzymes, galcanezumab possesses favourable and promising safety and tolerability.[A33112] Galcanezumab was given FDA approval on 27 September 2018.[L4894]
Indication/Disease	Galcanezumab is a humanized monoclonal antibody that is indicated for migraine prophylaxis and treatment of episodic cluster headaches in adults by binding endogenous human calcitonin gene-related peptide (CGRP).[A33112,L4894]
Pharmacodynamics	Galcanezumab is administered as a subcutaneous injection.[A33112,A33114,L4894] During clinical trials, it was noted that galcanezumab therapy resulted in a significant reduction in the mean number of migraine headache days and a good tolerability profile.[A33105] Additionally, post hoc efficacy analyses showed that 32% in the galcanezumab group versus 18% in the placebo group were complete responders.[A33105] Finally, the most commonly reported adverse events associated with galcanezumab use are headache, nasopharyngitis, hematuria, dermatitis, diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112]
Mechanism of Action	Galcanezumab is a fully humanized monoclonal antibody designed and manufactured specifically against calcitonin gene-related peptide (CGRP).[A33105,L4894] It binds avidly to human CGRP, with a binding affinity (Kd) of 31 pM (4.5 ng/mL). Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy.[A33090] Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients.[A33090] For all these reasons, the binding of CGRP to interfere with its activity was specifically designed to be the mechanism of action for galcanezumab to take advantage of in reversing the migraine-inducing activity of natural CGRP. The binding of galcanezumab to natural endogenous CGRP subsequently interferes with its activities, such as its binding to CGRP receptors, for example. Studies have also shown that humanized monoclonal antibodies against CGRP have proven successful in reducing the frequency of migraine headaches in early clinical trials as a preventative therapeutic.[A33112]
Toxicity	Overdose and LD₅₀ date are not readily available.[L4894] The most common adverse effects associated with galcanezumab during clinical trials include headache, nasopharyngitis, hematuria, and contact dermatitis.[A33112] However, with the exception of hematuria which was not present in placebo treatment arms, the frequencies of these events were similar to placebo.[A33112] Additional frequently reported adverse effects in subjects receiving galcanezumab were diarrhea, toothache, and increased alanine aminotransferase (ALT).[A33112] The pharmacokinetics of galcanezumab were not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), based on a population pharmacokinetic analysis.[L4894] Body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab.[L4894] Renal and hepatic impairment are not expected to affect the pharmacokinetics of galcanezumab.[L4894] Population pharmacokinetic analysis of integrated data from the galcanezumab clinical studies revealed that creatinine clearance did not affect the pharmacokinetics of galcanezumab in patients with mild or moderate renal impairment.[L4894] Patients with severe renal impairment (creatinine clearance <30 mL/min) have not been studied.[L4894] Based on a population PK analysis, bilirubin concentration did not significantly influence the CL/F of galcanezumab.[L4894] Studies regarding the carcinogenic potential and genetic toxicology of galcanezumab have not yet been conducted.[L4894] When galcanezumab (0, 30, or 250 mg/kg) was administered to male rats by subcutaneous injection prior to and during mating, no adverse effects on fertility was observed.[L4894] The higher dose tested was associated with a plasma exposure (Cave, ss) 8 times that in humans at the recommended human dose (RHD) of 120 mg.[L4894] When galcanezumab was administered to female rats by subcutaneous injection in two studies (0, 30, or 100 mg/kg; 0 or 250 mg/kg) prior to and during mating and continuing throughout organogenesis, no adverse effects on fertility were observed.[L4894] The highest dose tested (250 mg/kg) was associated with a plasma Cave, ss 38 times that in humans at the RHD.[L4894]
Metabolism	Monoclonal antibody agents like galcanezumab are not expected to generate toxic metabolites as they generally undergo proteolysis to their constituent amino acids.[F94] In particular, after administration galcanezumab is specifically expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous immunoglobulins.[L4894] Galcanezumab is also not believed to be metabolized by liver enzymes - making drug-drug interactions relatively unlikely.[L4894]
Absorption	Following single dose subcutaneous administration, the time to maximum concentration was recorded as 5 days.[L4894] The injection site location did not appear to significantly influence the absorption of galcanezumab.[L4894] The Cmax and the area under the concentration-time curve from dosing to infinity (AUC (0-8)) are generally considered to be dose proportional over a dose range.[A33112]
	The apparent volume of distribution of galcanezumab is documented to be 7.3 L, with 34% inter-individual variability.[L4894]
Clearance	It is noted that the clearance of galcanezumab is by proteolysis.[A33112] The apparent clearance of galcanezumab was recorded as 0.008 L/h.[L4894]
Categories	Serum Globulins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Calcitonin gene-related peptide 1,Calcitonin gene-related peptide 2
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	NA
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA