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Th1444 details

Primary information
ID	13884
Therapeutic ID	Th1444
Protein Name	Anifrolumab
Sequence	>Th1444_Anifrolumab EVQLVQSGAEVKKPGESLKISCKGSGYIFTNYWIAWVRQMPGKGLESMGIIYPGDSDIRYSPSFQGQVTISADKSITTAYLQWSSLKASDTAMYYCARHDIEGFDYWGRGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Molecular Weight	148000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The serum elimination half life anifrolumab in a phase 1 trial in patients with scleroderma was 0.84 days for a 0.1 mg/kg single dose, 1.24 days for a 0.3 mg/kg single dose, 2.96 days for a 1.0 mg/kg single dose, 4.07 days for a 3.0 mg/kg single dose, and 7.70 days for a 10.0 mg/kg single dose.[A237044]
Description	Anifrolumab, or MEDI-546, is a type 1 interferon receptor (IFNAR) inhibiting IgG1 monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[A237074,L34929] The standard therapy for systemic lupus erythematosus consists of antimalarials like [hydroxychloroquine], glucocorticoids like [dexamethasone], and disease modifying antirheumatic drugs like [methotrexate].[A237079,L34929] Three monoclonal antibodies (anifrolumab, [rontalizumab], and [sifalimumab]) that target the type 1 interferon pathway entered clinical trials as potential treatments for systemic lupus erythematosus, but so far only anifrolumab has been approved.[A237054] The design of early clinical trials of anti-interferon treatments such as anifrolumab, rontalizumab, and sifalimumab have come under criticism.[A237054] The design of the clinical trials use different definitions of autoantibody positivity, making comparison between trials difficult; all trials involve large portions of patients also using corticosteroids, which may alter patient responses in the experimental and placebo groups; and patient populations were largely homogenous, which may have increased the odds of success of the trial.[A237054] Anifrolumab has also been investigated for the treatment of Scleroderma.[A237044] Anifrolumab was granted FDA approval on 30 July 2021.[L34929]
Indication/Disease	Anifrolumab is indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[L34929]
Pharmacodynamics	Anifrolumab is a type 1 interferon receptor (IFNAR) inhibiting IgG1 monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[A237074,L34929] It has a long duration of action as it is given every 4 weeks.[L34929] Patients should be counselled regarding the risks of serious infections, hypersensitivity reactions, and malignancies.[L34929]
Mechanism of Action	Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple systems in the body.[A237059] SLE may manifest as a rash on the skin, and can progress to life-threatening autoimmune reactions in the kidney or nervous system.[A237069] Type 1 interferon pathway activation has been identified as a mediator of pathogenesis in SLE, and the level of type 1 interferon expression is correlated with severity of SLE.[A237059,A237069,A237084] Activation of the type 1 interferon receptor (INFAR1) by interferons alpha, beta, epsilon, kappa, and omega lead to stimulation of gene transcription.[A237059] Activation of INFAR1 and INFAR2 lead to phosphorylation of STAT1 and STAT2, which are translocated with interferon regulatory factor 9 (IRF9) to the cell nucleus to activate the interferon-stimulated response element (ISRE).[A237069] Activation of ISRE leads to the expression of many proinflammatory and immunomodulatory proteins, as well as the activation of a positive feedback loop that produces more type 1 interferons.[A237069] Interferon alpha stimulates monocytes to mature into myeloid dendritic cells that express self antigens.[A237084] CD4+ and CD8+ T-cells, as well as B cells, that are autoreactive will respond to the self antigens and induce inflammmation and apoptosis in cells.[A237084] This self-reactive immune response damages otherwise healthy tissue throughout the body.[A237084] Anifrolumab is an immunoglobulin gamma 1 kappa (IgG1) monoclonal antibody that selectively binds to subunit 1 of INFAR1.[A237049,L34929] The binding of anifrolumab to IFNAR1 inhibits the activity of the receptor, decreasing downstream signalling and gene transcription of inflammatory mediators.[A237059,L34929] The Fc region of anifrolumab carries the triple mutaion L234F/L235E/P331S to prevent binding of the Fc region of the antibody to cell surface Fc receptors.[A237069] In a phase IIb clinical trial, the primary endpoint was reached by 34.3% of patients in the 300 mg treatment group, 28.8% of patients in the 1000 mg treatment group, and 17.6% of patients in the placebo group.[A237059] Patients with higher interferon-stimulated gene transcription at baseline showed a greater response to treatment.[A237059]
Toxicity	Data regarding overdose is not readily available.[L34929] In a phase 1 clinical trial, patients given a single dose of 20.0 mg/kg experienced upper respiratory tract infections, headache, diarrhea, and nausea.[A237044] 2 patients in the 3.0 mg/kg single dose group experienced osteomyelitis and skin ulcer.[A237044] A single patient in the 1.0 mg/kg/week group developed chronic myelogenous leukemia.[A237044] The frequency and severity of adverse effects does not appear to be closely related to dose.[A237044] In the event of an overdose, treat patients with symptomatic and supportive measures.
Metabolism	Monoclonal antibodies are mainly catabolized to smaller oligopeptides and individual amino acids.[A40006,L34929]
Absorption	A 300 mg intravenous dose reaches a mean C_max of 82.4 µg/mL, with a T_max of 0.03 days, and an AUC of 907 day
	The estimated volume of distribution of anifrolumab at steady state is 6.23 L for a 69.1 kg patient.[L34929]
Clearance	The estimated systemic clearance of anifrolumab is 0.193 L/day.[L34929]
Categories	Amino Acids, Peptides, and Proteins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Interferon alpha/beta receptor 1
Brand Name	Saphnelo
Company	AstraZeneca Pharmaceuticals LP
Brand Description	AstraZeneca Pharmaceuticals LP
Prescribed For	Intravenous
Chemical Name	300 mg/2.0mL
Formulation	SAPHNELO is contraindicated in patients with a history of anaphylaxis with anifrolumab-fnia [see WARNINGS AND PRECAUTIONS].
Physical Appearance	runny or stuffy nose, upper respiratory tract infections, bronchitis, infusion related reactions, herpes zoster, and cough.
Route of Administration	Saphnelo is a prescription medicine used to treat adults with moderate to severe systemic lupus erythematosus (SLE or lupus) who are receiving other lupus medicines. Saphnelo contains anifrolumab-fnia which is in a group of medicines called monoclonal antibodies. Lupus is a disease of the immune system...
Recommended Dosage	Saphnelo is a prescription medicine used to treat the symptoms of Systemic Lupus Erythematosus. Saphnelo may be used alone or with other medications.
Contraindication	NA
Side Effects	Anifrolumab-fnia is a type I interferon (IFN) receptor antagonist, immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that is produced in mouse myeloma cells (NS0) by recombinant DNA technology. The molecular weight is approximately 148 kDa.
Useful Link 1	Link
Useful Link 2	Link
Remarks	NA

Primary information
ID	13885
Therapeutic ID	Th1444
Protein Name	Anifrolumab
Sequence	>Th1444_Anifrolumab EVQLVQSGAEVKKPGESLKISCKGSGYIFTNYWIAWVRQMPGKGLESMGIIYPGDSDIRYSPSFQGQVTISADKSITTAYLQWSSLKASDTAMYYCARHDIEGFDYWGRGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Molecular Weight	148000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The serum elimination half life anifrolumab in a phase 1 trial in patients with scleroderma was 0.84 days for a 0.1 mg/kg single dose, 1.24 days for a 0.3 mg/kg single dose, 2.96 days for a 1.0 mg/kg single dose, 4.07 days for a 3.0 mg/kg single dose, and 7.70 days for a 10.0 mg/kg single dose.[A237044]
Description	Anifrolumab, or MEDI-546, is a type 1 interferon receptor (IFNAR) inhibiting IgG1 monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[A237074,L34929] The standard therapy for systemic lupus erythematosus consists of antimalarials like [hydroxychloroquine], glucocorticoids like [dexamethasone], and disease modifying antirheumatic drugs like [methotrexate].[A237079,L34929] Three monoclonal antibodies (anifrolumab, [rontalizumab], and [sifalimumab]) that target the type 1 interferon pathway entered clinical trials as potential treatments for systemic lupus erythematosus, but so far only anifrolumab has been approved.[A237054] The design of early clinical trials of anti-interferon treatments such as anifrolumab, rontalizumab, and sifalimumab have come under criticism.[A237054] The design of the clinical trials use different definitions of autoantibody positivity, making comparison between trials difficult; all trials involve large portions of patients also using corticosteroids, which may alter patient responses in the experimental and placebo groups; and patient populations were largely homogenous, which may have increased the odds of success of the trial.[A237054] Anifrolumab has also been investigated for the treatment of Scleroderma.[A237044] Anifrolumab was granted FDA approval on 30 July 2021.[L34929]
Indication/Disease	Anifrolumab is indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[L34929]
Pharmacodynamics	Anifrolumab is a type 1 interferon receptor (IFNAR) inhibiting IgG1 monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[A237074,L34929] It has a long duration of action as it is given every 4 weeks.[L34929] Patients should be counselled regarding the risks of serious infections, hypersensitivity reactions, and malignancies.[L34929]
Mechanism of Action	Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple systems in the body.[A237059] SLE may manifest as a rash on the skin, and can progress to life-threatening autoimmune reactions in the kidney or nervous system.[A237069] Type 1 interferon pathway activation has been identified as a mediator of pathogenesis in SLE, and the level of type 1 interferon expression is correlated with severity of SLE.[A237059,A237069,A237084] Activation of the type 1 interferon receptor (INFAR1) by interferons alpha, beta, epsilon, kappa, and omega lead to stimulation of gene transcription.[A237059] Activation of INFAR1 and INFAR2 lead to phosphorylation of STAT1 and STAT2, which are translocated with interferon regulatory factor 9 (IRF9) to the cell nucleus to activate the interferon-stimulated response element (ISRE).[A237069] Activation of ISRE leads to the expression of many proinflammatory and immunomodulatory proteins, as well as the activation of a positive feedback loop that produces more type 1 interferons.[A237069] Interferon alpha stimulates monocytes to mature into myeloid dendritic cells that express self antigens.[A237084] CD4+ and CD8+ T-cells, as well as B cells, that are autoreactive will respond to the self antigens and induce inflammmation and apoptosis in cells.[A237084] This self-reactive immune response damages otherwise healthy tissue throughout the body.[A237084] Anifrolumab is an immunoglobulin gamma 1 kappa (IgG1) monoclonal antibody that selectively binds to subunit 1 of INFAR1.[A237049,L34929] The binding of anifrolumab to IFNAR1 inhibits the activity of the receptor, decreasing downstream signalling and gene transcription of inflammatory mediators.[A237059,L34929] The Fc region of anifrolumab carries the triple mutaion L234F/L235E/P331S to prevent binding of the Fc region of the antibody to cell surface Fc receptors.[A237069] In a phase IIb clinical trial, the primary endpoint was reached by 34.3% of patients in the 300 mg treatment group, 28.8% of patients in the 1000 mg treatment group, and 17.6% of patients in the placebo group.[A237059] Patients with higher interferon-stimulated gene transcription at baseline showed a greater response to treatment.[A237059]
Toxicity	Data regarding overdose is not readily available.[L34929] In a phase 1 clinical trial, patients given a single dose of 20.0 mg/kg experienced upper respiratory tract infections, headache, diarrhea, and nausea.[A237044] 2 patients in the 3.0 mg/kg single dose group experienced osteomyelitis and skin ulcer.[A237044] A single patient in the 1.0 mg/kg/week group developed chronic myelogenous leukemia.[A237044] The frequency and severity of adverse effects does not appear to be closely related to dose.[A237044] In the event of an overdose, treat patients with symptomatic and supportive measures.
Metabolism	Monoclonal antibodies are mainly catabolized to smaller oligopeptides and individual amino acids.[A40006,L34929]
Absorption	A 300 mg intravenous dose reaches a mean C_max of 82.4 µg/mL, with a T_max of 0.03 days, and an AUC of 907 day
	The estimated volume of distribution of anifrolumab at steady state is 6.23 L for a 69.1 kg patient.[L34929]
Clearance	The estimated systemic clearance of anifrolumab is 0.193 L/day.[L34929]
Categories	Antibodies
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Interferon alpha/beta receptor 1
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	13886
Therapeutic ID	Th1444
Protein Name	Anifrolumab
Sequence	>Th1444_Anifrolumab EVQLVQSGAEVKKPGESLKISCKGSGYIFTNYWIAWVRQMPGKGLESMGIIYPGDSDIRYSPSFQGQVTISADKSITTAYLQWSSLKASDTAMYYCARHDIEGFDYWGRGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Molecular Weight	148000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The serum elimination half life anifrolumab in a phase 1 trial in patients with scleroderma was 0.84 days for a 0.1 mg/kg single dose, 1.24 days for a 0.3 mg/kg single dose, 2.96 days for a 1.0 mg/kg single dose, 4.07 days for a 3.0 mg/kg single dose, and 7.70 days for a 10.0 mg/kg single dose.[A237044]
Description	Anifrolumab, or MEDI-546, is a type 1 interferon receptor (IFNAR) inhibiting IgG1 monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[A237074,L34929] The standard therapy for systemic lupus erythematosus consists of antimalarials like [hydroxychloroquine], glucocorticoids like [dexamethasone], and disease modifying antirheumatic drugs like [methotrexate].[A237079,L34929] Three monoclonal antibodies (anifrolumab, [rontalizumab], and [sifalimumab]) that target the type 1 interferon pathway entered clinical trials as potential treatments for systemic lupus erythematosus, but so far only anifrolumab has been approved.[A237054] The design of early clinical trials of anti-interferon treatments such as anifrolumab, rontalizumab, and sifalimumab have come under criticism.[A237054] The design of the clinical trials use different definitions of autoantibody positivity, making comparison between trials difficult; all trials involve large portions of patients also using corticosteroids, which may alter patient responses in the experimental and placebo groups; and patient populations were largely homogenous, which may have increased the odds of success of the trial.[A237054] Anifrolumab has also been investigated for the treatment of Scleroderma.[A237044] Anifrolumab was granted FDA approval on 30 July 2021.[L34929]
Indication/Disease	Anifrolumab is indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[L34929]
Pharmacodynamics	Anifrolumab is a type 1 interferon receptor (IFNAR) inhibiting IgG1 monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[A237074,L34929] It has a long duration of action as it is given every 4 weeks.[L34929] Patients should be counselled regarding the risks of serious infections, hypersensitivity reactions, and malignancies.[L34929]
Mechanism of Action	Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple systems in the body.[A237059] SLE may manifest as a rash on the skin, and can progress to life-threatening autoimmune reactions in the kidney or nervous system.[A237069] Type 1 interferon pathway activation has been identified as a mediator of pathogenesis in SLE, and the level of type 1 interferon expression is correlated with severity of SLE.[A237059,A237069,A237084] Activation of the type 1 interferon receptor (INFAR1) by interferons alpha, beta, epsilon, kappa, and omega lead to stimulation of gene transcription.[A237059] Activation of INFAR1 and INFAR2 lead to phosphorylation of STAT1 and STAT2, which are translocated with interferon regulatory factor 9 (IRF9) to the cell nucleus to activate the interferon-stimulated response element (ISRE).[A237069] Activation of ISRE leads to the expression of many proinflammatory and immunomodulatory proteins, as well as the activation of a positive feedback loop that produces more type 1 interferons.[A237069] Interferon alpha stimulates monocytes to mature into myeloid dendritic cells that express self antigens.[A237084] CD4+ and CD8+ T-cells, as well as B cells, that are autoreactive will respond to the self antigens and induce inflammmation and apoptosis in cells.[A237084] This self-reactive immune response damages otherwise healthy tissue throughout the body.[A237084] Anifrolumab is an immunoglobulin gamma 1 kappa (IgG1) monoclonal antibody that selectively binds to subunit 1 of INFAR1.[A237049,L34929] The binding of anifrolumab to IFNAR1 inhibits the activity of the receptor, decreasing downstream signalling and gene transcription of inflammatory mediators.[A237059,L34929] The Fc region of anifrolumab carries the triple mutaion L234F/L235E/P331S to prevent binding of the Fc region of the antibody to cell surface Fc receptors.[A237069] In a phase IIb clinical trial, the primary endpoint was reached by 34.3% of patients in the 300 mg treatment group, 28.8% of patients in the 1000 mg treatment group, and 17.6% of patients in the placebo group.[A237059] Patients with higher interferon-stimulated gene transcription at baseline showed a greater response to treatment.[A237059]
Toxicity	Data regarding overdose is not readily available.[L34929] In a phase 1 clinical trial, patients given a single dose of 20.0 mg/kg experienced upper respiratory tract infections, headache, diarrhea, and nausea.[A237044] 2 patients in the 3.0 mg/kg single dose group experienced osteomyelitis and skin ulcer.[A237044] A single patient in the 1.0 mg/kg/week group developed chronic myelogenous leukemia.[A237044] The frequency and severity of adverse effects does not appear to be closely related to dose.[A237044] In the event of an overdose, treat patients with symptomatic and supportive measures.
Metabolism	Monoclonal antibodies are mainly catabolized to smaller oligopeptides and individual amino acids.[A40006,L34929]
Absorption	A 300 mg intravenous dose reaches a mean C_max of 82.4 µg/mL, with a T_max of 0.03 days, and an AUC of 907 day
	The estimated volume of distribution of anifrolumab at steady state is 6.23 L for a 69.1 kg patient.[L34929]
Clearance	The estimated systemic clearance of anifrolumab is 0.193 L/day.[L34929]
Categories	Blood Proteins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Interferon alpha/beta receptor 1
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	13887
Therapeutic ID	Th1444
Protein Name	Anifrolumab
Sequence	>Th1444_Anifrolumab EVQLVQSGAEVKKPGESLKISCKGSGYIFTNYWIAWVRQMPGKGLESMGIIYPGDSDIRYSPSFQGQVTISADKSITTAYLQWSSLKASDTAMYYCARHDIEGFDYWGRGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Molecular Weight	148000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The serum elimination half life anifrolumab in a phase 1 trial in patients with scleroderma was 0.84 days for a 0.1 mg/kg single dose, 1.24 days for a 0.3 mg/kg single dose, 2.96 days for a 1.0 mg/kg single dose, 4.07 days for a 3.0 mg/kg single dose, and 7.70 days for a 10.0 mg/kg single dose.[A237044]
Description	Anifrolumab, or MEDI-546, is a type 1 interferon receptor (IFNAR) inhibiting IgG1 monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[A237074,L34929] The standard therapy for systemic lupus erythematosus consists of antimalarials like [hydroxychloroquine], glucocorticoids like [dexamethasone], and disease modifying antirheumatic drugs like [methotrexate].[A237079,L34929] Three monoclonal antibodies (anifrolumab, [rontalizumab], and [sifalimumab]) that target the type 1 interferon pathway entered clinical trials as potential treatments for systemic lupus erythematosus, but so far only anifrolumab has been approved.[A237054] The design of early clinical trials of anti-interferon treatments such as anifrolumab, rontalizumab, and sifalimumab have come under criticism.[A237054] The design of the clinical trials use different definitions of autoantibody positivity, making comparison between trials difficult; all trials involve large portions of patients also using corticosteroids, which may alter patient responses in the experimental and placebo groups; and patient populations were largely homogenous, which may have increased the odds of success of the trial.[A237054] Anifrolumab has also been investigated for the treatment of Scleroderma.[A237044] Anifrolumab was granted FDA approval on 30 July 2021.[L34929]
Indication/Disease	Anifrolumab is indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[L34929]
Pharmacodynamics	Anifrolumab is a type 1 interferon receptor (IFNAR) inhibiting IgG1 monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[A237074,L34929] It has a long duration of action as it is given every 4 weeks.[L34929] Patients should be counselled regarding the risks of serious infections, hypersensitivity reactions, and malignancies.[L34929]
Mechanism of Action	Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple systems in the body.[A237059] SLE may manifest as a rash on the skin, and can progress to life-threatening autoimmune reactions in the kidney or nervous system.[A237069] Type 1 interferon pathway activation has been identified as a mediator of pathogenesis in SLE, and the level of type 1 interferon expression is correlated with severity of SLE.[A237059,A237069,A237084] Activation of the type 1 interferon receptor (INFAR1) by interferons alpha, beta, epsilon, kappa, and omega lead to stimulation of gene transcription.[A237059] Activation of INFAR1 and INFAR2 lead to phosphorylation of STAT1 and STAT2, which are translocated with interferon regulatory factor 9 (IRF9) to the cell nucleus to activate the interferon-stimulated response element (ISRE).[A237069] Activation of ISRE leads to the expression of many proinflammatory and immunomodulatory proteins, as well as the activation of a positive feedback loop that produces more type 1 interferons.[A237069] Interferon alpha stimulates monocytes to mature into myeloid dendritic cells that express self antigens.[A237084] CD4+ and CD8+ T-cells, as well as B cells, that are autoreactive will respond to the self antigens and induce inflammmation and apoptosis in cells.[A237084] This self-reactive immune response damages otherwise healthy tissue throughout the body.[A237084] Anifrolumab is an immunoglobulin gamma 1 kappa (IgG1) monoclonal antibody that selectively binds to subunit 1 of INFAR1.[A237049,L34929] The binding of anifrolumab to IFNAR1 inhibits the activity of the receptor, decreasing downstream signalling and gene transcription of inflammatory mediators.[A237059,L34929] The Fc region of anifrolumab carries the triple mutaion L234F/L235E/P331S to prevent binding of the Fc region of the antibody to cell surface Fc receptors.[A237069] In a phase IIb clinical trial, the primary endpoint was reached by 34.3% of patients in the 300 mg treatment group, 28.8% of patients in the 1000 mg treatment group, and 17.6% of patients in the placebo group.[A237059] Patients with higher interferon-stimulated gene transcription at baseline showed a greater response to treatment.[A237059]
Toxicity	Data regarding overdose is not readily available.[L34929] In a phase 1 clinical trial, patients given a single dose of 20.0 mg/kg experienced upper respiratory tract infections, headache, diarrhea, and nausea.[A237044] 2 patients in the 3.0 mg/kg single dose group experienced osteomyelitis and skin ulcer.[A237044] A single patient in the 1.0 mg/kg/week group developed chronic myelogenous leukemia.[A237044] The frequency and severity of adverse effects does not appear to be closely related to dose.[A237044] In the event of an overdose, treat patients with symptomatic and supportive measures.
Metabolism	Monoclonal antibodies are mainly catabolized to smaller oligopeptides and individual amino acids.[A40006,L34929]
Absorption	A 300 mg intravenous dose reaches a mean C_max of 82.4 µg/mL, with a T_max of 0.03 days, and an AUC of 907 day
	The estimated volume of distribution of anifrolumab at steady state is 6.23 L for a 69.1 kg patient.[L34929]
Clearance	The estimated systemic clearance of anifrolumab is 0.193 L/day.[L34929]
Categories	Globulins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Interferon alpha/beta receptor 1
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	13888
Therapeutic ID	Th1444
Protein Name	Anifrolumab
Sequence	>Th1444_Anifrolumab EVQLVQSGAEVKKPGESLKISCKGSGYIFTNYWIAWVRQMPGKGLESMGIIYPGDSDIRYSPSFQGQVTISADKSITTAYLQWSSLKASDTAMYYCARHDIEGFDYWGRGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Molecular Weight	148000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The serum elimination half life anifrolumab in a phase 1 trial in patients with scleroderma was 0.84 days for a 0.1 mg/kg single dose, 1.24 days for a 0.3 mg/kg single dose, 2.96 days for a 1.0 mg/kg single dose, 4.07 days for a 3.0 mg/kg single dose, and 7.70 days for a 10.0 mg/kg single dose.[A237044]
Description	Anifrolumab, or MEDI-546, is a type 1 interferon receptor (IFNAR) inhibiting IgG1 monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[A237074,L34929] The standard therapy for systemic lupus erythematosus consists of antimalarials like [hydroxychloroquine], glucocorticoids like [dexamethasone], and disease modifying antirheumatic drugs like [methotrexate].[A237079,L34929] Three monoclonal antibodies (anifrolumab, [rontalizumab], and [sifalimumab]) that target the type 1 interferon pathway entered clinical trials as potential treatments for systemic lupus erythematosus, but so far only anifrolumab has been approved.[A237054] The design of early clinical trials of anti-interferon treatments such as anifrolumab, rontalizumab, and sifalimumab have come under criticism.[A237054] The design of the clinical trials use different definitions of autoantibody positivity, making comparison between trials difficult; all trials involve large portions of patients also using corticosteroids, which may alter patient responses in the experimental and placebo groups; and patient populations were largely homogenous, which may have increased the odds of success of the trial.[A237054] Anifrolumab has also been investigated for the treatment of Scleroderma.[A237044] Anifrolumab was granted FDA approval on 30 July 2021.[L34929]
Indication/Disease	Anifrolumab is indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[L34929]
Pharmacodynamics	Anifrolumab is a type 1 interferon receptor (IFNAR) inhibiting IgG1 monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[A237074,L34929] It has a long duration of action as it is given every 4 weeks.[L34929] Patients should be counselled regarding the risks of serious infections, hypersensitivity reactions, and malignancies.[L34929]
Mechanism of Action	Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple systems in the body.[A237059] SLE may manifest as a rash on the skin, and can progress to life-threatening autoimmune reactions in the kidney or nervous system.[A237069] Type 1 interferon pathway activation has been identified as a mediator of pathogenesis in SLE, and the level of type 1 interferon expression is correlated with severity of SLE.[A237059,A237069,A237084] Activation of the type 1 interferon receptor (INFAR1) by interferons alpha, beta, epsilon, kappa, and omega lead to stimulation of gene transcription.[A237059] Activation of INFAR1 and INFAR2 lead to phosphorylation of STAT1 and STAT2, which are translocated with interferon regulatory factor 9 (IRF9) to the cell nucleus to activate the interferon-stimulated response element (ISRE).[A237069] Activation of ISRE leads to the expression of many proinflammatory and immunomodulatory proteins, as well as the activation of a positive feedback loop that produces more type 1 interferons.[A237069] Interferon alpha stimulates monocytes to mature into myeloid dendritic cells that express self antigens.[A237084] CD4+ and CD8+ T-cells, as well as B cells, that are autoreactive will respond to the self antigens and induce inflammmation and apoptosis in cells.[A237084] This self-reactive immune response damages otherwise healthy tissue throughout the body.[A237084] Anifrolumab is an immunoglobulin gamma 1 kappa (IgG1) monoclonal antibody that selectively binds to subunit 1 of INFAR1.[A237049,L34929] The binding of anifrolumab to IFNAR1 inhibits the activity of the receptor, decreasing downstream signalling and gene transcription of inflammatory mediators.[A237059,L34929] The Fc region of anifrolumab carries the triple mutaion L234F/L235E/P331S to prevent binding of the Fc region of the antibody to cell surface Fc receptors.[A237069] In a phase IIb clinical trial, the primary endpoint was reached by 34.3% of patients in the 300 mg treatment group, 28.8% of patients in the 1000 mg treatment group, and 17.6% of patients in the placebo group.[A237059] Patients with higher interferon-stimulated gene transcription at baseline showed a greater response to treatment.[A237059]
Toxicity	Data regarding overdose is not readily available.[L34929] In a phase 1 clinical trial, patients given a single dose of 20.0 mg/kg experienced upper respiratory tract infections, headache, diarrhea, and nausea.[A237044] 2 patients in the 3.0 mg/kg single dose group experienced osteomyelitis and skin ulcer.[A237044] A single patient in the 1.0 mg/kg/week group developed chronic myelogenous leukemia.[A237044] The frequency and severity of adverse effects does not appear to be closely related to dose.[A237044] In the event of an overdose, treat patients with symptomatic and supportive measures.
Metabolism	Monoclonal antibodies are mainly catabolized to smaller oligopeptides and individual amino acids.[A40006,L34929]
Absorption	A 300 mg intravenous dose reaches a mean C_max of 82.4 µg/mL, with a T_max of 0.03 days, and an AUC of 907 day
	The estimated volume of distribution of anifrolumab at steady state is 6.23 L for a 69.1 kg patient.[L34929]
Clearance	The estimated systemic clearance of anifrolumab is 0.193 L/day.[L34929]
Categories	Immunoglobulins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Interferon alpha/beta receptor 1
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	13889
Therapeutic ID	Th1444
Protein Name	Anifrolumab
Sequence	>Th1444_Anifrolumab EVQLVQSGAEVKKPGESLKISCKGSGYIFTNYWIAWVRQMPGKGLESMGIIYPGDSDIRYSPSFQGQVTISADKSITTAYLQWSSLKASDTAMYYCARHDIEGFDYWGRGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Molecular Weight	148000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The serum elimination half life anifrolumab in a phase 1 trial in patients with scleroderma was 0.84 days for a 0.1 mg/kg single dose, 1.24 days for a 0.3 mg/kg single dose, 2.96 days for a 1.0 mg/kg single dose, 4.07 days for a 3.0 mg/kg single dose, and 7.70 days for a 10.0 mg/kg single dose.[A237044]
Description	Anifrolumab, or MEDI-546, is a type 1 interferon receptor (IFNAR) inhibiting IgG1 monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[A237074,L34929] The standard therapy for systemic lupus erythematosus consists of antimalarials like [hydroxychloroquine], glucocorticoids like [dexamethasone], and disease modifying antirheumatic drugs like [methotrexate].[A237079,L34929] Three monoclonal antibodies (anifrolumab, [rontalizumab], and [sifalimumab]) that target the type 1 interferon pathway entered clinical trials as potential treatments for systemic lupus erythematosus, but so far only anifrolumab has been approved.[A237054] The design of early clinical trials of anti-interferon treatments such as anifrolumab, rontalizumab, and sifalimumab have come under criticism.[A237054] The design of the clinical trials use different definitions of autoantibody positivity, making comparison between trials difficult; all trials involve large portions of patients also using corticosteroids, which may alter patient responses in the experimental and placebo groups; and patient populations were largely homogenous, which may have increased the odds of success of the trial.[A237054] Anifrolumab has also been investigated for the treatment of Scleroderma.[A237044] Anifrolumab was granted FDA approval on 30 July 2021.[L34929]
Indication/Disease	Anifrolumab is indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[L34929]
Pharmacodynamics	Anifrolumab is a type 1 interferon receptor (IFNAR) inhibiting IgG1 monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[A237074,L34929] It has a long duration of action as it is given every 4 weeks.[L34929] Patients should be counselled regarding the risks of serious infections, hypersensitivity reactions, and malignancies.[L34929]
Mechanism of Action	Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple systems in the body.[A237059] SLE may manifest as a rash on the skin, and can progress to life-threatening autoimmune reactions in the kidney or nervous system.[A237069] Type 1 interferon pathway activation has been identified as a mediator of pathogenesis in SLE, and the level of type 1 interferon expression is correlated with severity of SLE.[A237059,A237069,A237084] Activation of the type 1 interferon receptor (INFAR1) by interferons alpha, beta, epsilon, kappa, and omega lead to stimulation of gene transcription.[A237059] Activation of INFAR1 and INFAR2 lead to phosphorylation of STAT1 and STAT2, which are translocated with interferon regulatory factor 9 (IRF9) to the cell nucleus to activate the interferon-stimulated response element (ISRE).[A237069] Activation of ISRE leads to the expression of many proinflammatory and immunomodulatory proteins, as well as the activation of a positive feedback loop that produces more type 1 interferons.[A237069] Interferon alpha stimulates monocytes to mature into myeloid dendritic cells that express self antigens.[A237084] CD4+ and CD8+ T-cells, as well as B cells, that are autoreactive will respond to the self antigens and induce inflammmation and apoptosis in cells.[A237084] This self-reactive immune response damages otherwise healthy tissue throughout the body.[A237084] Anifrolumab is an immunoglobulin gamma 1 kappa (IgG1) monoclonal antibody that selectively binds to subunit 1 of INFAR1.[A237049,L34929] The binding of anifrolumab to IFNAR1 inhibits the activity of the receptor, decreasing downstream signalling and gene transcription of inflammatory mediators.[A237059,L34929] The Fc region of anifrolumab carries the triple mutaion L234F/L235E/P331S to prevent binding of the Fc region of the antibody to cell surface Fc receptors.[A237069] In a phase IIb clinical trial, the primary endpoint was reached by 34.3% of patients in the 300 mg treatment group, 28.8% of patients in the 1000 mg treatment group, and 17.6% of patients in the placebo group.[A237059] Patients with higher interferon-stimulated gene transcription at baseline showed a greater response to treatment.[A237059]
Toxicity	Data regarding overdose is not readily available.[L34929] In a phase 1 clinical trial, patients given a single dose of 20.0 mg/kg experienced upper respiratory tract infections, headache, diarrhea, and nausea.[A237044] 2 patients in the 3.0 mg/kg single dose group experienced osteomyelitis and skin ulcer.[A237044] A single patient in the 1.0 mg/kg/week group developed chronic myelogenous leukemia.[A237044] The frequency and severity of adverse effects does not appear to be closely related to dose.[A237044] In the event of an overdose, treat patients with symptomatic and supportive measures.
Metabolism	Monoclonal antibodies are mainly catabolized to smaller oligopeptides and individual amino acids.[A40006,L34929]
Absorption	A 300 mg intravenous dose reaches a mean C_max of 82.4 µg/mL, with a T_max of 0.03 days, and an AUC of 907 day
	The estimated volume of distribution of anifrolumab at steady state is 6.23 L for a 69.1 kg patient.[L34929]
Clearance	The estimated systemic clearance of anifrolumab is 0.193 L/day.[L34929]
Categories	Immunoproteins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Interferon alpha/beta receptor 1
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	13890
Therapeutic ID	Th1444
Protein Name	Anifrolumab
Sequence	>Th1444_Anifrolumab EVQLVQSGAEVKKPGESLKISCKGSGYIFTNYWIAWVRQMPGKGLESMGIIYPGDSDIRYSPSFQGQVTISADKSITTAYLQWSSLKASDTAMYYCARHDIEGFDYWGRGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Molecular Weight	148000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The serum elimination half life anifrolumab in a phase 1 trial in patients with scleroderma was 0.84 days for a 0.1 mg/kg single dose, 1.24 days for a 0.3 mg/kg single dose, 2.96 days for a 1.0 mg/kg single dose, 4.07 days for a 3.0 mg/kg single dose, and 7.70 days for a 10.0 mg/kg single dose.[A237044]
Description	Anifrolumab, or MEDI-546, is a type 1 interferon receptor (IFNAR) inhibiting IgG1 monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[A237074,L34929] The standard therapy for systemic lupus erythematosus consists of antimalarials like [hydroxychloroquine], glucocorticoids like [dexamethasone], and disease modifying antirheumatic drugs like [methotrexate].[A237079,L34929] Three monoclonal antibodies (anifrolumab, [rontalizumab], and [sifalimumab]) that target the type 1 interferon pathway entered clinical trials as potential treatments for systemic lupus erythematosus, but so far only anifrolumab has been approved.[A237054] The design of early clinical trials of anti-interferon treatments such as anifrolumab, rontalizumab, and sifalimumab have come under criticism.[A237054] The design of the clinical trials use different definitions of autoantibody positivity, making comparison between trials difficult; all trials involve large portions of patients also using corticosteroids, which may alter patient responses in the experimental and placebo groups; and patient populations were largely homogenous, which may have increased the odds of success of the trial.[A237054] Anifrolumab has also been investigated for the treatment of Scleroderma.[A237044] Anifrolumab was granted FDA approval on 30 July 2021.[L34929]
Indication/Disease	Anifrolumab is indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[L34929]
Pharmacodynamics	Anifrolumab is a type 1 interferon receptor (IFNAR) inhibiting IgG1 monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[A237074,L34929] It has a long duration of action as it is given every 4 weeks.[L34929] Patients should be counselled regarding the risks of serious infections, hypersensitivity reactions, and malignancies.[L34929]
Mechanism of Action	Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple systems in the body.[A237059] SLE may manifest as a rash on the skin, and can progress to life-threatening autoimmune reactions in the kidney or nervous system.[A237069] Type 1 interferon pathway activation has been identified as a mediator of pathogenesis in SLE, and the level of type 1 interferon expression is correlated with severity of SLE.[A237059,A237069,A237084] Activation of the type 1 interferon receptor (INFAR1) by interferons alpha, beta, epsilon, kappa, and omega lead to stimulation of gene transcription.[A237059] Activation of INFAR1 and INFAR2 lead to phosphorylation of STAT1 and STAT2, which are translocated with interferon regulatory factor 9 (IRF9) to the cell nucleus to activate the interferon-stimulated response element (ISRE).[A237069] Activation of ISRE leads to the expression of many proinflammatory and immunomodulatory proteins, as well as the activation of a positive feedback loop that produces more type 1 interferons.[A237069] Interferon alpha stimulates monocytes to mature into myeloid dendritic cells that express self antigens.[A237084] CD4+ and CD8+ T-cells, as well as B cells, that are autoreactive will respond to the self antigens and induce inflammmation and apoptosis in cells.[A237084] This self-reactive immune response damages otherwise healthy tissue throughout the body.[A237084] Anifrolumab is an immunoglobulin gamma 1 kappa (IgG1) monoclonal antibody that selectively binds to subunit 1 of INFAR1.[A237049,L34929] The binding of anifrolumab to IFNAR1 inhibits the activity of the receptor, decreasing downstream signalling and gene transcription of inflammatory mediators.[A237059,L34929] The Fc region of anifrolumab carries the triple mutaion L234F/L235E/P331S to prevent binding of the Fc region of the antibody to cell surface Fc receptors.[A237069] In a phase IIb clinical trial, the primary endpoint was reached by 34.3% of patients in the 300 mg treatment group, 28.8% of patients in the 1000 mg treatment group, and 17.6% of patients in the placebo group.[A237059] Patients with higher interferon-stimulated gene transcription at baseline showed a greater response to treatment.[A237059]
Toxicity	Data regarding overdose is not readily available.[L34929] In a phase 1 clinical trial, patients given a single dose of 20.0 mg/kg experienced upper respiratory tract infections, headache, diarrhea, and nausea.[A237044] 2 patients in the 3.0 mg/kg single dose group experienced osteomyelitis and skin ulcer.[A237044] A single patient in the 1.0 mg/kg/week group developed chronic myelogenous leukemia.[A237044] The frequency and severity of adverse effects does not appear to be closely related to dose.[A237044] In the event of an overdose, treat patients with symptomatic and supportive measures.
Metabolism	Monoclonal antibodies are mainly catabolized to smaller oligopeptides and individual amino acids.[A40006,L34929]
Absorption	A 300 mg intravenous dose reaches a mean C_max of 82.4 µg/mL, with a T_max of 0.03 days, and an AUC of 907 day
	The estimated volume of distribution of anifrolumab at steady state is 6.23 L for a 69.1 kg patient.[L34929]
Clearance	The estimated systemic clearance of anifrolumab is 0.193 L/day.[L34929]
Categories	Proteins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Interferon alpha/beta receptor 1
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	13891
Therapeutic ID	Th1444
Protein Name	Anifrolumab
Sequence	>Th1444_Anifrolumab EVQLVQSGAEVKKPGESLKISCKGSGYIFTNYWIAWVRQMPGKGLESMGIIYPGDSDIRYSPSFQGQVTISADKSITTAYLQWSSLKASDTAMYYCARHDIEGFDYWGRGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Molecular Weight	148000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The serum elimination half life anifrolumab in a phase 1 trial in patients with scleroderma was 0.84 days for a 0.1 mg/kg single dose, 1.24 days for a 0.3 mg/kg single dose, 2.96 days for a 1.0 mg/kg single dose, 4.07 days for a 3.0 mg/kg single dose, and 7.70 days for a 10.0 mg/kg single dose.[A237044]
Description	Anifrolumab, or MEDI-546, is a type 1 interferon receptor (IFNAR) inhibiting IgG1 monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[A237074,L34929] The standard therapy for systemic lupus erythematosus consists of antimalarials like [hydroxychloroquine], glucocorticoids like [dexamethasone], and disease modifying antirheumatic drugs like [methotrexate].[A237079,L34929] Three monoclonal antibodies (anifrolumab, [rontalizumab], and [sifalimumab]) that target the type 1 interferon pathway entered clinical trials as potential treatments for systemic lupus erythematosus, but so far only anifrolumab has been approved.[A237054] The design of early clinical trials of anti-interferon treatments such as anifrolumab, rontalizumab, and sifalimumab have come under criticism.[A237054] The design of the clinical trials use different definitions of autoantibody positivity, making comparison between trials difficult; all trials involve large portions of patients also using corticosteroids, which may alter patient responses in the experimental and placebo groups; and patient populations were largely homogenous, which may have increased the odds of success of the trial.[A237054] Anifrolumab has also been investigated for the treatment of Scleroderma.[A237044] Anifrolumab was granted FDA approval on 30 July 2021.[L34929]
Indication/Disease	Anifrolumab is indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[L34929]
Pharmacodynamics	Anifrolumab is a type 1 interferon receptor (IFNAR) inhibiting IgG1 monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[A237074,L34929] It has a long duration of action as it is given every 4 weeks.[L34929] Patients should be counselled regarding the risks of serious infections, hypersensitivity reactions, and malignancies.[L34929]
Mechanism of Action	Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple systems in the body.[A237059] SLE may manifest as a rash on the skin, and can progress to life-threatening autoimmune reactions in the kidney or nervous system.[A237069] Type 1 interferon pathway activation has been identified as a mediator of pathogenesis in SLE, and the level of type 1 interferon expression is correlated with severity of SLE.[A237059,A237069,A237084] Activation of the type 1 interferon receptor (INFAR1) by interferons alpha, beta, epsilon, kappa, and omega lead to stimulation of gene transcription.[A237059] Activation of INFAR1 and INFAR2 lead to phosphorylation of STAT1 and STAT2, which are translocated with interferon regulatory factor 9 (IRF9) to the cell nucleus to activate the interferon-stimulated response element (ISRE).[A237069] Activation of ISRE leads to the expression of many proinflammatory and immunomodulatory proteins, as well as the activation of a positive feedback loop that produces more type 1 interferons.[A237069] Interferon alpha stimulates monocytes to mature into myeloid dendritic cells that express self antigens.[A237084] CD4+ and CD8+ T-cells, as well as B cells, that are autoreactive will respond to the self antigens and induce inflammmation and apoptosis in cells.[A237084] This self-reactive immune response damages otherwise healthy tissue throughout the body.[A237084] Anifrolumab is an immunoglobulin gamma 1 kappa (IgG1) monoclonal antibody that selectively binds to subunit 1 of INFAR1.[A237049,L34929] The binding of anifrolumab to IFNAR1 inhibits the activity of the receptor, decreasing downstream signalling and gene transcription of inflammatory mediators.[A237059,L34929] The Fc region of anifrolumab carries the triple mutaion L234F/L235E/P331S to prevent binding of the Fc region of the antibody to cell surface Fc receptors.[A237069] In a phase IIb clinical trial, the primary endpoint was reached by 34.3% of patients in the 300 mg treatment group, 28.8% of patients in the 1000 mg treatment group, and 17.6% of patients in the placebo group.[A237059] Patients with higher interferon-stimulated gene transcription at baseline showed a greater response to treatment.[A237059]
Toxicity	Data regarding overdose is not readily available.[L34929] In a phase 1 clinical trial, patients given a single dose of 20.0 mg/kg experienced upper respiratory tract infections, headache, diarrhea, and nausea.[A237044] 2 patients in the 3.0 mg/kg single dose group experienced osteomyelitis and skin ulcer.[A237044] A single patient in the 1.0 mg/kg/week group developed chronic myelogenous leukemia.[A237044] The frequency and severity of adverse effects does not appear to be closely related to dose.[A237044] In the event of an overdose, treat patients with symptomatic and supportive measures.
Metabolism	Monoclonal antibodies are mainly catabolized to smaller oligopeptides and individual amino acids.[A40006,L34929]
Absorption	A 300 mg intravenous dose reaches a mean C_max of 82.4 µg/mL, with a T_max of 0.03 days, and an AUC of 907 day
	The estimated volume of distribution of anifrolumab at steady state is 6.23 L for a 69.1 kg patient.[L34929]
Clearance	The estimated systemic clearance of anifrolumab is 0.193 L/day.[L34929]
Categories	Serum Globulins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Interferon alpha/beta receptor 1
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	13892
Therapeutic ID	Th1444
Protein Name	Anifrolumab
Sequence	>Th1444_Anifrolumab EVQLVQSGAEVKKPGESLKISCKGSGYIFTNYWIAWVRQMPGKGLESMGIIYPGDSDIRYSPSFQGQVTISADKSITTAYLQWSSLKASDTAMYYCARHDIEGFDYWGRGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Molecular Weight	148000
Chemical Formula	NA
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	The serum elimination half life anifrolumab in a phase 1 trial in patients with scleroderma was 0.84 days for a 0.1 mg/kg single dose, 1.24 days for a 0.3 mg/kg single dose, 2.96 days for a 1.0 mg/kg single dose, 4.07 days for a 3.0 mg/kg single dose, and 7.70 days for a 10.0 mg/kg single dose.[A237044]
Description	Anifrolumab, or MEDI-546, is a type 1 interferon receptor (IFNAR) inhibiting IgG1 monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[A237074,L34929] The standard therapy for systemic lupus erythematosus consists of antimalarials like [hydroxychloroquine], glucocorticoids like [dexamethasone], and disease modifying antirheumatic drugs like [methotrexate].[A237079,L34929] Three monoclonal antibodies (anifrolumab, [rontalizumab], and [sifalimumab]) that target the type 1 interferon pathway entered clinical trials as potential treatments for systemic lupus erythematosus, but so far only anifrolumab has been approved.[A237054] The design of early clinical trials of anti-interferon treatments such as anifrolumab, rontalizumab, and sifalimumab have come under criticism.[A237054] The design of the clinical trials use different definitions of autoantibody positivity, making comparison between trials difficult; all trials involve large portions of patients also using corticosteroids, which may alter patient responses in the experimental and placebo groups; and patient populations were largely homogenous, which may have increased the odds of success of the trial.[A237054] Anifrolumab has also been investigated for the treatment of Scleroderma.[A237044] Anifrolumab was granted FDA approval on 30 July 2021.[L34929]
Indication/Disease	Anifrolumab is indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[L34929]
Pharmacodynamics	Anifrolumab is a type 1 interferon receptor (IFNAR) inhibiting IgG1 monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.[A237074,L34929] It has a long duration of action as it is given every 4 weeks.[L34929] Patients should be counselled regarding the risks of serious infections, hypersensitivity reactions, and malignancies.[L34929]
Mechanism of Action	Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple systems in the body.[A237059] SLE may manifest as a rash on the skin, and can progress to life-threatening autoimmune reactions in the kidney or nervous system.[A237069] Type 1 interferon pathway activation has been identified as a mediator of pathogenesis in SLE, and the level of type 1 interferon expression is correlated with severity of SLE.[A237059,A237069,A237084] Activation of the type 1 interferon receptor (INFAR1) by interferons alpha, beta, epsilon, kappa, and omega lead to stimulation of gene transcription.[A237059] Activation of INFAR1 and INFAR2 lead to phosphorylation of STAT1 and STAT2, which are translocated with interferon regulatory factor 9 (IRF9) to the cell nucleus to activate the interferon-stimulated response element (ISRE).[A237069] Activation of ISRE leads to the expression of many proinflammatory and immunomodulatory proteins, as well as the activation of a positive feedback loop that produces more type 1 interferons.[A237069] Interferon alpha stimulates monocytes to mature into myeloid dendritic cells that express self antigens.[A237084] CD4+ and CD8+ T-cells, as well as B cells, that are autoreactive will respond to the self antigens and induce inflammmation and apoptosis in cells.[A237084] This self-reactive immune response damages otherwise healthy tissue throughout the body.[A237084] Anifrolumab is an immunoglobulin gamma 1 kappa (IgG1) monoclonal antibody that selectively binds to subunit 1 of INFAR1.[A237049,L34929] The binding of anifrolumab to IFNAR1 inhibits the activity of the receptor, decreasing downstream signalling and gene transcription of inflammatory mediators.[A237059,L34929] The Fc region of anifrolumab carries the triple mutaion L234F/L235E/P331S to prevent binding of the Fc region of the antibody to cell surface Fc receptors.[A237069] In a phase IIb clinical trial, the primary endpoint was reached by 34.3% of patients in the 300 mg treatment group, 28.8% of patients in the 1000 mg treatment group, and 17.6% of patients in the placebo group.[A237059] Patients with higher interferon-stimulated gene transcription at baseline showed a greater response to treatment.[A237059]
Toxicity	Data regarding overdose is not readily available.[L34929] In a phase 1 clinical trial, patients given a single dose of 20.0 mg/kg experienced upper respiratory tract infections, headache, diarrhea, and nausea.[A237044] 2 patients in the 3.0 mg/kg single dose group experienced osteomyelitis and skin ulcer.[A237044] A single patient in the 1.0 mg/kg/week group developed chronic myelogenous leukemia.[A237044] The frequency and severity of adverse effects does not appear to be closely related to dose.[A237044] In the event of an overdose, treat patients with symptomatic and supportive measures.
Metabolism	Monoclonal antibodies are mainly catabolized to smaller oligopeptides and individual amino acids.[A40006,L34929]
Absorption	A 300 mg intravenous dose reaches a mean C_max of 82.4 µg/mL, with a T_max of 0.03 days, and an AUC of 907 day
	The estimated volume of distribution of anifrolumab at steady state is 6.23 L for a 69.1 kg patient.[L34929]
Clearance	The estimated systemic clearance of anifrolumab is 0.193 L/day.[L34929]
Categories	Type I Interferon Receptor Antagonist
Patents Number	NA
Date of Issue	NA
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Drug Interaction	NA
Target	Interferon alpha/beta receptor 1
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Route of Administration	NA
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Contraindication	NA
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Useful Link 1	Link
Useful Link 2	NA
Remarks	NA