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Th1670 details

Primary information
ID	16062
Therapeutic ID	Th1670
Protein Name	Tixagevimab
Sequence	NA
Molecular Weight	149000
Chemical Formula	C6488H10034N1746O2038S50
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	Tixagevimab has a half-life of 87.9 ± 13.9 days.[L39411]
Description	SARS-CoV-2, the causative agent of COVID-19, enters cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Blocking the interaction between the receptor-binding domain (RBD) of the S1 subunit and ACE2 inhibits viral host cell entry; animal studies indicate that antibodies capable of blocking this interaction reduce viral load and improve clinical symptoms of infection.[A243356, A243361] Tixagevimab (formerly AZD8895) is a recombinant monoclonal antibody produced in Chinese hamster ovary (CHO) cells derived from a neutralizing antibody isolated from a patient with a natural history of SARS-CoV-2 infection and modified through targeted amino acid substitutions to exhibit an extended (~85-day) half-life.[A243351, A243356, L39411] As the RBD binding site of tixagevimab does not overlap with that of [cilgavimab], the two can be administered to synergistically impair SARS-CoV-2 infection in individuals who may be exposed to the virus.[A243351, A243361, L39411] Tixagevimab is not approved for any indication by the FDA. Tixagevimab, in combination with [cilgavimab], was issued an FDA emergency use authorization (EUA) on December 9, 2021, for the pre-exposure prophylaxis of COVID-19 in individuals at increased risk for whom vaccination is not recommended. The combination is co-packaged and available under the name EVUSHELD (formerly AZD7442).[L39411]
Indication/Disease	Tixagevimab has been issued an emergency use authorization (EUA) by the FDA, in combination with [cilgavimab], for the pre-exposure prophylaxis of COVID-19 in adult and pediatric patients aged 12 years and older weighing at least 40 kg. Furthermore, patients must not be currently infected with SARS-CoV-2 or have had known exposure to an individual infected with SARS-CoV-2 and must either be immunocompromised due to a medical condition, medication, or treatment or be otherwise ineligible for vaccination with any eligible COVID-19 vaccine due to a history of severe adverse reactions.[L39411] The combination of tixagevimab and [cilgavimab] is not authorized for the treatment or post-exposure prophylaxis of COVID-19 and is not a substitute for COVID-19 vaccination. Individuals receiving therapy following COVID-19 vaccination should wait at least two weeks.[L39411]
Pharmacodynamics	Tixagevimab is an extended half-life recombinant human IgG1 monoclonal antibody directed against the SARS-CoV-2 spike (S) protein. Administered concurrently with [cilgavimab], the combination carries a risk of hypersensitivity reactions and requires caution when administering to patients with thrombocytopenia or a coagulation disorder. Based on limited clinical experience, caution should also be exercised in patients with cardiac risk factors or a history of cardiovascular disease. As there is limited experience with this combination, unexpected serious adverse events may occur.[L39411]
Mechanism of Action	SARS-CoV-2, the causative agent of COVID-19, enters cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Of the two subunits comprising the trimeric S glycoprotein, the S1 subunit binds ACE2 via its receptor-binding domain (RBD) while the central S2 subunit mediates fusion following S1 shedding.[A243351, A243356] Large-scale screens suggest that the most potently neutralizing antibodies recovered from the B cells of those convalescing following natural infection with SARS-CoV-2 bind to the RBD of S1 and are capable of disrupting the interaction between the RBD and human ACE2.[A243356] Tixagevimab (AZD8895)is a recombinant human IgG1 monoclonal antibody based on a neutralizing antibody (COV2-2196) isolated from patients with a natural history of SARS-CoV-2 infection and modified through specific amino acid substitutions to extend its half-life and reduce antibody effector functions.[L39411] Tixagevimab binds to a non-overlapping region of the S1 RBD as [cilgavimab] but is only capable of binding the S protein in its "up" conformation (K_D of 2.76 pM).[A243356, A243361, L39411] Cell culture studies suggest little to no antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), or antibody-dependent natural killer cell activation (ADNKA), suggesting the protective effect is due solely to inhibition of the RBD-ACE2 interaction. Tixagevimab inhibits RBD-ACE2 binding with an IC₅₀ of 0.32 nM (48 ng/mL) and neutralizes SARS-CoV-2 (strain USA-WA1/2020) in a cellular assay with an EC₅₀ value of 60.7 pM (9 ng/mL).[L39411] As with other antiviral treatments, there is a risk of resistant variants emerging during treatment. Experiments to identify escape variants during culture of recombinant vesicular stomatitis virus expressing the S protein (VSV-SARS-CoV-2) or authentic SARS-CoV-2 (strain USA-WA1/2020) identified K444E, K444R, and R346I as potential single-nucleotide escape variants for [cilgavimab] (conferring a >200-fold reduction in susceptibility). However, no escape variants were identified to tixagevimab or the combination of [cilgavimab] and tixagevimab.[A243361, L39411]
Toxicity	Toxicity information regarding tixagevimab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects. Symptomatic and supportive measures are recommended.[L39411]
Metabolism	As a monoclonal antibody, tixagevimab is expected to undergo proteolytic degradation.[L39411]
Absorption	A single 150 mg intramuscular dose of tixagevimab, given concurrently with 150 mg of [cilgavimab], resulted in a C_max geometric mean (%CV) of 16.5 (35.6) µg/mL in a median T_max of 14.0 (range 3.1-30) days. The observed geometric mean (%CV) one, 150, or 210 days following dosing was 4.4 (92.2), 6.6 (25.6), and 4.0 (31.6) µg/mL. This single dose resulted in an AUC_0-8 of 2529 (30.2) µg
	Tixagevimab has an apparent volume of distribution of 7.7 ± 1.97 L.[L39411]
Clearance	Tixagevimab has an apparent clearance of 0.062 ± 0.019 L/day.[L39411]
Categories	Amino Acids, Peptides, and Proteins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Spike glycoprotein
Brand Name	Evusheld
Company	AstraZeneca Pharmaceuticals LP
Brand Description	AstraZeneca Pharmaceuticals LP
Prescribed For	Intramuscular; Intravenous
Chemical Name	NA
Formulation	NA
Physical Appearance	Most common treatment-emergent adverse events occurring in ≥3% of individuals (median duration of follow-up of 83 days): Headache (6%), fatigue (4%), and cough (3%).
Route of Administration	Cilgavimab in combination with tixagevimab is an experimental medicine being studied for the prevention before exposure of COVID-19. It is not yet known if Evusheld is safe and effective. The US Food and Drug Administration (FDA) has authorized emergency use of cilgavimab in combination with another...
Recommended Dosage	NA
Contraindication	NA
Side Effects	NA
Useful Link 1	Link
Useful Link 2	Link
Remarks	NA

Primary information
ID	16063
Therapeutic ID	Th1670
Protein Name	Tixagevimab
Sequence	NA
Molecular Weight	149000
Chemical Formula	C6488H10034N1746O2038S50
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	Tixagevimab has a half-life of 87.9 ± 13.9 days.[L39411]
Description	SARS-CoV-2, the causative agent of COVID-19, enters cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Blocking the interaction between the receptor-binding domain (RBD) of the S1 subunit and ACE2 inhibits viral host cell entry; animal studies indicate that antibodies capable of blocking this interaction reduce viral load and improve clinical symptoms of infection.[A243356, A243361] Tixagevimab (formerly AZD8895) is a recombinant monoclonal antibody produced in Chinese hamster ovary (CHO) cells derived from a neutralizing antibody isolated from a patient with a natural history of SARS-CoV-2 infection and modified through targeted amino acid substitutions to exhibit an extended (~85-day) half-life.[A243351, A243356, L39411] As the RBD binding site of tixagevimab does not overlap with that of [cilgavimab], the two can be administered to synergistically impair SARS-CoV-2 infection in individuals who may be exposed to the virus.[A243351, A243361, L39411] Tixagevimab is not approved for any indication by the FDA. Tixagevimab, in combination with [cilgavimab], was issued an FDA emergency use authorization (EUA) on December 9, 2021, for the pre-exposure prophylaxis of COVID-19 in individuals at increased risk for whom vaccination is not recommended. The combination is co-packaged and available under the name EVUSHELD (formerly AZD7442).[L39411]
Indication/Disease	Tixagevimab has been issued an emergency use authorization (EUA) by the FDA, in combination with [cilgavimab], for the pre-exposure prophylaxis of COVID-19 in adult and pediatric patients aged 12 years and older weighing at least 40 kg. Furthermore, patients must not be currently infected with SARS-CoV-2 or have had known exposure to an individual infected with SARS-CoV-2 and must either be immunocompromised due to a medical condition, medication, or treatment or be otherwise ineligible for vaccination with any eligible COVID-19 vaccine due to a history of severe adverse reactions.[L39411] The combination of tixagevimab and [cilgavimab] is not authorized for the treatment or post-exposure prophylaxis of COVID-19 and is not a substitute for COVID-19 vaccination. Individuals receiving therapy following COVID-19 vaccination should wait at least two weeks.[L39411]
Pharmacodynamics	Tixagevimab is an extended half-life recombinant human IgG1 monoclonal antibody directed against the SARS-CoV-2 spike (S) protein. Administered concurrently with [cilgavimab], the combination carries a risk of hypersensitivity reactions and requires caution when administering to patients with thrombocytopenia or a coagulation disorder. Based on limited clinical experience, caution should also be exercised in patients with cardiac risk factors or a history of cardiovascular disease. As there is limited experience with this combination, unexpected serious adverse events may occur.[L39411]
Mechanism of Action	SARS-CoV-2, the causative agent of COVID-19, enters cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Of the two subunits comprising the trimeric S glycoprotein, the S1 subunit binds ACE2 via its receptor-binding domain (RBD) while the central S2 subunit mediates fusion following S1 shedding.[A243351, A243356] Large-scale screens suggest that the most potently neutralizing antibodies recovered from the B cells of those convalescing following natural infection with SARS-CoV-2 bind to the RBD of S1 and are capable of disrupting the interaction between the RBD and human ACE2.[A243356] Tixagevimab (AZD8895)is a recombinant human IgG1 monoclonal antibody based on a neutralizing antibody (COV2-2196) isolated from patients with a natural history of SARS-CoV-2 infection and modified through specific amino acid substitutions to extend its half-life and reduce antibody effector functions.[L39411] Tixagevimab binds to a non-overlapping region of the S1 RBD as [cilgavimab] but is only capable of binding the S protein in its "up" conformation (K_D of 2.76 pM).[A243356, A243361, L39411] Cell culture studies suggest little to no antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), or antibody-dependent natural killer cell activation (ADNKA), suggesting the protective effect is due solely to inhibition of the RBD-ACE2 interaction. Tixagevimab inhibits RBD-ACE2 binding with an IC₅₀ of 0.32 nM (48 ng/mL) and neutralizes SARS-CoV-2 (strain USA-WA1/2020) in a cellular assay with an EC₅₀ value of 60.7 pM (9 ng/mL).[L39411] As with other antiviral treatments, there is a risk of resistant variants emerging during treatment. Experiments to identify escape variants during culture of recombinant vesicular stomatitis virus expressing the S protein (VSV-SARS-CoV-2) or authentic SARS-CoV-2 (strain USA-WA1/2020) identified K444E, K444R, and R346I as potential single-nucleotide escape variants for [cilgavimab] (conferring a >200-fold reduction in susceptibility). However, no escape variants were identified to tixagevimab or the combination of [cilgavimab] and tixagevimab.[A243361, L39411]
Toxicity	Toxicity information regarding tixagevimab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects. Symptomatic and supportive measures are recommended.[L39411]
Metabolism	As a monoclonal antibody, tixagevimab is expected to undergo proteolytic degradation.[L39411]
Absorption	A single 150 mg intramuscular dose of tixagevimab, given concurrently with 150 mg of [cilgavimab], resulted in a C_max geometric mean (%CV) of 16.5 (35.6) µg/mL in a median T_max of 14.0 (range 3.1-30) days. The observed geometric mean (%CV) one, 150, or 210 days following dosing was 4.4 (92.2), 6.6 (25.6), and 4.0 (31.6) µg/mL. This single dose resulted in an AUC_0-8 of 2529 (30.2) µg
	Tixagevimab has an apparent volume of distribution of 7.7 ± 1.97 L.[L39411]
Clearance	Tixagevimab has an apparent clearance of 0.062 ± 0.019 L/day.[L39411]
Categories	Antibodies, Monoclonal
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Spike glycoprotein
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	16064
Therapeutic ID	Th1670
Protein Name	Tixagevimab
Sequence	NA
Molecular Weight	149000
Chemical Formula	C6488H10034N1746O2038S50
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	Tixagevimab has a half-life of 87.9 ± 13.9 days.[L39411]
Description	SARS-CoV-2, the causative agent of COVID-19, enters cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Blocking the interaction between the receptor-binding domain (RBD) of the S1 subunit and ACE2 inhibits viral host cell entry; animal studies indicate that antibodies capable of blocking this interaction reduce viral load and improve clinical symptoms of infection.[A243356, A243361] Tixagevimab (formerly AZD8895) is a recombinant monoclonal antibody produced in Chinese hamster ovary (CHO) cells derived from a neutralizing antibody isolated from a patient with a natural history of SARS-CoV-2 infection and modified through targeted amino acid substitutions to exhibit an extended (~85-day) half-life.[A243351, A243356, L39411] As the RBD binding site of tixagevimab does not overlap with that of [cilgavimab], the two can be administered to synergistically impair SARS-CoV-2 infection in individuals who may be exposed to the virus.[A243351, A243361, L39411] Tixagevimab is not approved for any indication by the FDA. Tixagevimab, in combination with [cilgavimab], was issued an FDA emergency use authorization (EUA) on December 9, 2021, for the pre-exposure prophylaxis of COVID-19 in individuals at increased risk for whom vaccination is not recommended. The combination is co-packaged and available under the name EVUSHELD (formerly AZD7442).[L39411]
Indication/Disease	Tixagevimab has been issued an emergency use authorization (EUA) by the FDA, in combination with [cilgavimab], for the pre-exposure prophylaxis of COVID-19 in adult and pediatric patients aged 12 years and older weighing at least 40 kg. Furthermore, patients must not be currently infected with SARS-CoV-2 or have had known exposure to an individual infected with SARS-CoV-2 and must either be immunocompromised due to a medical condition, medication, or treatment or be otherwise ineligible for vaccination with any eligible COVID-19 vaccine due to a history of severe adverse reactions.[L39411] The combination of tixagevimab and [cilgavimab] is not authorized for the treatment or post-exposure prophylaxis of COVID-19 and is not a substitute for COVID-19 vaccination. Individuals receiving therapy following COVID-19 vaccination should wait at least two weeks.[L39411]
Pharmacodynamics	Tixagevimab is an extended half-life recombinant human IgG1 monoclonal antibody directed against the SARS-CoV-2 spike (S) protein. Administered concurrently with [cilgavimab], the combination carries a risk of hypersensitivity reactions and requires caution when administering to patients with thrombocytopenia or a coagulation disorder. Based on limited clinical experience, caution should also be exercised in patients with cardiac risk factors or a history of cardiovascular disease. As there is limited experience with this combination, unexpected serious adverse events may occur.[L39411]
Mechanism of Action	SARS-CoV-2, the causative agent of COVID-19, enters cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Of the two subunits comprising the trimeric S glycoprotein, the S1 subunit binds ACE2 via its receptor-binding domain (RBD) while the central S2 subunit mediates fusion following S1 shedding.[A243351, A243356] Large-scale screens suggest that the most potently neutralizing antibodies recovered from the B cells of those convalescing following natural infection with SARS-CoV-2 bind to the RBD of S1 and are capable of disrupting the interaction between the RBD and human ACE2.[A243356] Tixagevimab (AZD8895)is a recombinant human IgG1 monoclonal antibody based on a neutralizing antibody (COV2-2196) isolated from patients with a natural history of SARS-CoV-2 infection and modified through specific amino acid substitutions to extend its half-life and reduce antibody effector functions.[L39411] Tixagevimab binds to a non-overlapping region of the S1 RBD as [cilgavimab] but is only capable of binding the S protein in its "up" conformation (K_D of 2.76 pM).[A243356, A243361, L39411] Cell culture studies suggest little to no antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), or antibody-dependent natural killer cell activation (ADNKA), suggesting the protective effect is due solely to inhibition of the RBD-ACE2 interaction. Tixagevimab inhibits RBD-ACE2 binding with an IC₅₀ of 0.32 nM (48 ng/mL) and neutralizes SARS-CoV-2 (strain USA-WA1/2020) in a cellular assay with an EC₅₀ value of 60.7 pM (9 ng/mL).[L39411] As with other antiviral treatments, there is a risk of resistant variants emerging during treatment. Experiments to identify escape variants during culture of recombinant vesicular stomatitis virus expressing the S protein (VSV-SARS-CoV-2) or authentic SARS-CoV-2 (strain USA-WA1/2020) identified K444E, K444R, and R346I as potential single-nucleotide escape variants for [cilgavimab] (conferring a >200-fold reduction in susceptibility). However, no escape variants were identified to tixagevimab or the combination of [cilgavimab] and tixagevimab.[A243361, L39411]
Toxicity	Toxicity information regarding tixagevimab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects. Symptomatic and supportive measures are recommended.[L39411]
Metabolism	As a monoclonal antibody, tixagevimab is expected to undergo proteolytic degradation.[L39411]
Absorption	A single 150 mg intramuscular dose of tixagevimab, given concurrently with 150 mg of [cilgavimab], resulted in a C_max geometric mean (%CV) of 16.5 (35.6) µg/mL in a median T_max of 14.0 (range 3.1-30) days. The observed geometric mean (%CV) one, 150, or 210 days following dosing was 4.4 (92.2), 6.6 (25.6), and 4.0 (31.6) µg/mL. This single dose resulted in an AUC_0-8 of 2529 (30.2) µg
	Tixagevimab has an apparent volume of distribution of 7.7 ± 1.97 L.[L39411]
Clearance	Tixagevimab has an apparent clearance of 0.062 ± 0.019 L/day.[L39411]
Categories	Antiviral Agents
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Spike glycoprotein
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	16065
Therapeutic ID	Th1670
Protein Name	Tixagevimab
Sequence	NA
Molecular Weight	149000
Chemical Formula	C6488H10034N1746O2038S50
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	Tixagevimab has a half-life of 87.9 ± 13.9 days.[L39411]
Description	SARS-CoV-2, the causative agent of COVID-19, enters cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Blocking the interaction between the receptor-binding domain (RBD) of the S1 subunit and ACE2 inhibits viral host cell entry; animal studies indicate that antibodies capable of blocking this interaction reduce viral load and improve clinical symptoms of infection.[A243356, A243361] Tixagevimab (formerly AZD8895) is a recombinant monoclonal antibody produced in Chinese hamster ovary (CHO) cells derived from a neutralizing antibody isolated from a patient with a natural history of SARS-CoV-2 infection and modified through targeted amino acid substitutions to exhibit an extended (~85-day) half-life.[A243351, A243356, L39411] As the RBD binding site of tixagevimab does not overlap with that of [cilgavimab], the two can be administered to synergistically impair SARS-CoV-2 infection in individuals who may be exposed to the virus.[A243351, A243361, L39411] Tixagevimab is not approved for any indication by the FDA. Tixagevimab, in combination with [cilgavimab], was issued an FDA emergency use authorization (EUA) on December 9, 2021, for the pre-exposure prophylaxis of COVID-19 in individuals at increased risk for whom vaccination is not recommended. The combination is co-packaged and available under the name EVUSHELD (formerly AZD7442).[L39411]
Indication/Disease	Tixagevimab has been issued an emergency use authorization (EUA) by the FDA, in combination with [cilgavimab], for the pre-exposure prophylaxis of COVID-19 in adult and pediatric patients aged 12 years and older weighing at least 40 kg. Furthermore, patients must not be currently infected with SARS-CoV-2 or have had known exposure to an individual infected with SARS-CoV-2 and must either be immunocompromised due to a medical condition, medication, or treatment or be otherwise ineligible for vaccination with any eligible COVID-19 vaccine due to a history of severe adverse reactions.[L39411] The combination of tixagevimab and [cilgavimab] is not authorized for the treatment or post-exposure prophylaxis of COVID-19 and is not a substitute for COVID-19 vaccination. Individuals receiving therapy following COVID-19 vaccination should wait at least two weeks.[L39411]
Pharmacodynamics	Tixagevimab is an extended half-life recombinant human IgG1 monoclonal antibody directed against the SARS-CoV-2 spike (S) protein. Administered concurrently with [cilgavimab], the combination carries a risk of hypersensitivity reactions and requires caution when administering to patients with thrombocytopenia or a coagulation disorder. Based on limited clinical experience, caution should also be exercised in patients with cardiac risk factors or a history of cardiovascular disease. As there is limited experience with this combination, unexpected serious adverse events may occur.[L39411]
Mechanism of Action	SARS-CoV-2, the causative agent of COVID-19, enters cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Of the two subunits comprising the trimeric S glycoprotein, the S1 subunit binds ACE2 via its receptor-binding domain (RBD) while the central S2 subunit mediates fusion following S1 shedding.[A243351, A243356] Large-scale screens suggest that the most potently neutralizing antibodies recovered from the B cells of those convalescing following natural infection with SARS-CoV-2 bind to the RBD of S1 and are capable of disrupting the interaction between the RBD and human ACE2.[A243356] Tixagevimab (AZD8895)is a recombinant human IgG1 monoclonal antibody based on a neutralizing antibody (COV2-2196) isolated from patients with a natural history of SARS-CoV-2 infection and modified through specific amino acid substitutions to extend its half-life and reduce antibody effector functions.[L39411] Tixagevimab binds to a non-overlapping region of the S1 RBD as [cilgavimab] but is only capable of binding the S protein in its "up" conformation (K_D of 2.76 pM).[A243356, A243361, L39411] Cell culture studies suggest little to no antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), or antibody-dependent natural killer cell activation (ADNKA), suggesting the protective effect is due solely to inhibition of the RBD-ACE2 interaction. Tixagevimab inhibits RBD-ACE2 binding with an IC₅₀ of 0.32 nM (48 ng/mL) and neutralizes SARS-CoV-2 (strain USA-WA1/2020) in a cellular assay with an EC₅₀ value of 60.7 pM (9 ng/mL).[L39411] As with other antiviral treatments, there is a risk of resistant variants emerging during treatment. Experiments to identify escape variants during culture of recombinant vesicular stomatitis virus expressing the S protein (VSV-SARS-CoV-2) or authentic SARS-CoV-2 (strain USA-WA1/2020) identified K444E, K444R, and R346I as potential single-nucleotide escape variants for [cilgavimab] (conferring a >200-fold reduction in susceptibility). However, no escape variants were identified to tixagevimab or the combination of [cilgavimab] and tixagevimab.[A243361, L39411]
Toxicity	Toxicity information regarding tixagevimab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects. Symptomatic and supportive measures are recommended.[L39411]
Metabolism	As a monoclonal antibody, tixagevimab is expected to undergo proteolytic degradation.[L39411]
Absorption	A single 150 mg intramuscular dose of tixagevimab, given concurrently with 150 mg of [cilgavimab], resulted in a C_max geometric mean (%CV) of 16.5 (35.6) µg/mL in a median T_max of 14.0 (range 3.1-30) days. The observed geometric mean (%CV) one, 150, or 210 days following dosing was 4.4 (92.2), 6.6 (25.6), and 4.0 (31.6) µg/mL. This single dose resulted in an AUC_0-8 of 2529 (30.2) µg
	Tixagevimab has an apparent volume of distribution of 7.7 ± 1.97 L.[L39411]
Clearance	Tixagevimab has an apparent clearance of 0.062 ± 0.019 L/day.[L39411]
Categories	Antivirals for Systemic Use
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Spike glycoprotein
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	16066
Therapeutic ID	Th1670
Protein Name	Tixagevimab
Sequence	NA
Molecular Weight	149000
Chemical Formula	C6488H10034N1746O2038S50
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	Tixagevimab has a half-life of 87.9 ± 13.9 days.[L39411]
Description	SARS-CoV-2, the causative agent of COVID-19, enters cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Blocking the interaction between the receptor-binding domain (RBD) of the S1 subunit and ACE2 inhibits viral host cell entry; animal studies indicate that antibodies capable of blocking this interaction reduce viral load and improve clinical symptoms of infection.[A243356, A243361] Tixagevimab (formerly AZD8895) is a recombinant monoclonal antibody produced in Chinese hamster ovary (CHO) cells derived from a neutralizing antibody isolated from a patient with a natural history of SARS-CoV-2 infection and modified through targeted amino acid substitutions to exhibit an extended (~85-day) half-life.[A243351, A243356, L39411] As the RBD binding site of tixagevimab does not overlap with that of [cilgavimab], the two can be administered to synergistically impair SARS-CoV-2 infection in individuals who may be exposed to the virus.[A243351, A243361, L39411] Tixagevimab is not approved for any indication by the FDA. Tixagevimab, in combination with [cilgavimab], was issued an FDA emergency use authorization (EUA) on December 9, 2021, for the pre-exposure prophylaxis of COVID-19 in individuals at increased risk for whom vaccination is not recommended. The combination is co-packaged and available under the name EVUSHELD (formerly AZD7442).[L39411]
Indication/Disease	Tixagevimab has been issued an emergency use authorization (EUA) by the FDA, in combination with [cilgavimab], for the pre-exposure prophylaxis of COVID-19 in adult and pediatric patients aged 12 years and older weighing at least 40 kg. Furthermore, patients must not be currently infected with SARS-CoV-2 or have had known exposure to an individual infected with SARS-CoV-2 and must either be immunocompromised due to a medical condition, medication, or treatment or be otherwise ineligible for vaccination with any eligible COVID-19 vaccine due to a history of severe adverse reactions.[L39411] The combination of tixagevimab and [cilgavimab] is not authorized for the treatment or post-exposure prophylaxis of COVID-19 and is not a substitute for COVID-19 vaccination. Individuals receiving therapy following COVID-19 vaccination should wait at least two weeks.[L39411]
Pharmacodynamics	Tixagevimab is an extended half-life recombinant human IgG1 monoclonal antibody directed against the SARS-CoV-2 spike (S) protein. Administered concurrently with [cilgavimab], the combination carries a risk of hypersensitivity reactions and requires caution when administering to patients with thrombocytopenia or a coagulation disorder. Based on limited clinical experience, caution should also be exercised in patients with cardiac risk factors or a history of cardiovascular disease. As there is limited experience with this combination, unexpected serious adverse events may occur.[L39411]
Mechanism of Action	SARS-CoV-2, the causative agent of COVID-19, enters cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Of the two subunits comprising the trimeric S glycoprotein, the S1 subunit binds ACE2 via its receptor-binding domain (RBD) while the central S2 subunit mediates fusion following S1 shedding.[A243351, A243356] Large-scale screens suggest that the most potently neutralizing antibodies recovered from the B cells of those convalescing following natural infection with SARS-CoV-2 bind to the RBD of S1 and are capable of disrupting the interaction between the RBD and human ACE2.[A243356] Tixagevimab (AZD8895)is a recombinant human IgG1 monoclonal antibody based on a neutralizing antibody (COV2-2196) isolated from patients with a natural history of SARS-CoV-2 infection and modified through specific amino acid substitutions to extend its half-life and reduce antibody effector functions.[L39411] Tixagevimab binds to a non-overlapping region of the S1 RBD as [cilgavimab] but is only capable of binding the S protein in its "up" conformation (K_D of 2.76 pM).[A243356, A243361, L39411] Cell culture studies suggest little to no antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), or antibody-dependent natural killer cell activation (ADNKA), suggesting the protective effect is due solely to inhibition of the RBD-ACE2 interaction. Tixagevimab inhibits RBD-ACE2 binding with an IC₅₀ of 0.32 nM (48 ng/mL) and neutralizes SARS-CoV-2 (strain USA-WA1/2020) in a cellular assay with an EC₅₀ value of 60.7 pM (9 ng/mL).[L39411] As with other antiviral treatments, there is a risk of resistant variants emerging during treatment. Experiments to identify escape variants during culture of recombinant vesicular stomatitis virus expressing the S protein (VSV-SARS-CoV-2) or authentic SARS-CoV-2 (strain USA-WA1/2020) identified K444E, K444R, and R346I as potential single-nucleotide escape variants for [cilgavimab] (conferring a >200-fold reduction in susceptibility). However, no escape variants were identified to tixagevimab or the combination of [cilgavimab] and tixagevimab.[A243361, L39411]
Toxicity	Toxicity information regarding tixagevimab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects. Symptomatic and supportive measures are recommended.[L39411]
Metabolism	As a monoclonal antibody, tixagevimab is expected to undergo proteolytic degradation.[L39411]
Absorption	A single 150 mg intramuscular dose of tixagevimab, given concurrently with 150 mg of [cilgavimab], resulted in a C_max geometric mean (%CV) of 16.5 (35.6) µg/mL in a median T_max of 14.0 (range 3.1-30) days. The observed geometric mean (%CV) one, 150, or 210 days following dosing was 4.4 (92.2), 6.6 (25.6), and 4.0 (31.6) µg/mL. This single dose resulted in an AUC_0-8 of 2529 (30.2) µg
	Tixagevimab has an apparent volume of distribution of 7.7 ± 1.97 L.[L39411]
Clearance	Tixagevimab has an apparent clearance of 0.062 ± 0.019 L/day.[L39411]
Categories	Blood Proteins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Spike glycoprotein
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	16067
Therapeutic ID	Th1670
Protein Name	Tixagevimab
Sequence	NA
Molecular Weight	149000
Chemical Formula	C6488H10034N1746O2038S50
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	Tixagevimab has a half-life of 87.9 ± 13.9 days.[L39411]
Description	SARS-CoV-2, the causative agent of COVID-19, enters cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Blocking the interaction between the receptor-binding domain (RBD) of the S1 subunit and ACE2 inhibits viral host cell entry; animal studies indicate that antibodies capable of blocking this interaction reduce viral load and improve clinical symptoms of infection.[A243356, A243361] Tixagevimab (formerly AZD8895) is a recombinant monoclonal antibody produced in Chinese hamster ovary (CHO) cells derived from a neutralizing antibody isolated from a patient with a natural history of SARS-CoV-2 infection and modified through targeted amino acid substitutions to exhibit an extended (~85-day) half-life.[A243351, A243356, L39411] As the RBD binding site of tixagevimab does not overlap with that of [cilgavimab], the two can be administered to synergistically impair SARS-CoV-2 infection in individuals who may be exposed to the virus.[A243351, A243361, L39411] Tixagevimab is not approved for any indication by the FDA. Tixagevimab, in combination with [cilgavimab], was issued an FDA emergency use authorization (EUA) on December 9, 2021, for the pre-exposure prophylaxis of COVID-19 in individuals at increased risk for whom vaccination is not recommended. The combination is co-packaged and available under the name EVUSHELD (formerly AZD7442).[L39411]
Indication/Disease	Tixagevimab has been issued an emergency use authorization (EUA) by the FDA, in combination with [cilgavimab], for the pre-exposure prophylaxis of COVID-19 in adult and pediatric patients aged 12 years and older weighing at least 40 kg. Furthermore, patients must not be currently infected with SARS-CoV-2 or have had known exposure to an individual infected with SARS-CoV-2 and must either be immunocompromised due to a medical condition, medication, or treatment or be otherwise ineligible for vaccination with any eligible COVID-19 vaccine due to a history of severe adverse reactions.[L39411] The combination of tixagevimab and [cilgavimab] is not authorized for the treatment or post-exposure prophylaxis of COVID-19 and is not a substitute for COVID-19 vaccination. Individuals receiving therapy following COVID-19 vaccination should wait at least two weeks.[L39411]
Pharmacodynamics	Tixagevimab is an extended half-life recombinant human IgG1 monoclonal antibody directed against the SARS-CoV-2 spike (S) protein. Administered concurrently with [cilgavimab], the combination carries a risk of hypersensitivity reactions and requires caution when administering to patients with thrombocytopenia or a coagulation disorder. Based on limited clinical experience, caution should also be exercised in patients with cardiac risk factors or a history of cardiovascular disease. As there is limited experience with this combination, unexpected serious adverse events may occur.[L39411]
Mechanism of Action	SARS-CoV-2, the causative agent of COVID-19, enters cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Of the two subunits comprising the trimeric S glycoprotein, the S1 subunit binds ACE2 via its receptor-binding domain (RBD) while the central S2 subunit mediates fusion following S1 shedding.[A243351, A243356] Large-scale screens suggest that the most potently neutralizing antibodies recovered from the B cells of those convalescing following natural infection with SARS-CoV-2 bind to the RBD of S1 and are capable of disrupting the interaction between the RBD and human ACE2.[A243356] Tixagevimab (AZD8895)is a recombinant human IgG1 monoclonal antibody based on a neutralizing antibody (COV2-2196) isolated from patients with a natural history of SARS-CoV-2 infection and modified through specific amino acid substitutions to extend its half-life and reduce antibody effector functions.[L39411] Tixagevimab binds to a non-overlapping region of the S1 RBD as [cilgavimab] but is only capable of binding the S protein in its "up" conformation (K_D of 2.76 pM).[A243356, A243361, L39411] Cell culture studies suggest little to no antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), or antibody-dependent natural killer cell activation (ADNKA), suggesting the protective effect is due solely to inhibition of the RBD-ACE2 interaction. Tixagevimab inhibits RBD-ACE2 binding with an IC₅₀ of 0.32 nM (48 ng/mL) and neutralizes SARS-CoV-2 (strain USA-WA1/2020) in a cellular assay with an EC₅₀ value of 60.7 pM (9 ng/mL).[L39411] As with other antiviral treatments, there is a risk of resistant variants emerging during treatment. Experiments to identify escape variants during culture of recombinant vesicular stomatitis virus expressing the S protein (VSV-SARS-CoV-2) or authentic SARS-CoV-2 (strain USA-WA1/2020) identified K444E, K444R, and R346I as potential single-nucleotide escape variants for [cilgavimab] (conferring a >200-fold reduction in susceptibility). However, no escape variants were identified to tixagevimab or the combination of [cilgavimab] and tixagevimab.[A243361, L39411]
Toxicity	Toxicity information regarding tixagevimab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects. Symptomatic and supportive measures are recommended.[L39411]
Metabolism	As a monoclonal antibody, tixagevimab is expected to undergo proteolytic degradation.[L39411]
Absorption	A single 150 mg intramuscular dose of tixagevimab, given concurrently with 150 mg of [cilgavimab], resulted in a C_max geometric mean (%CV) of 16.5 (35.6) µg/mL in a median T_max of 14.0 (range 3.1-30) days. The observed geometric mean (%CV) one, 150, or 210 days following dosing was 4.4 (92.2), 6.6 (25.6), and 4.0 (31.6) µg/mL. This single dose resulted in an AUC_0-8 of 2529 (30.2) µg
	Tixagevimab has an apparent volume of distribution of 7.7 ± 1.97 L.[L39411]
Clearance	Tixagevimab has an apparent clearance of 0.062 ± 0.019 L/day.[L39411]
Categories	Experimental Unapproved Treatments for COVID-19
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Spike glycoprotein
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	16068
Therapeutic ID	Th1670
Protein Name	Tixagevimab
Sequence	NA
Molecular Weight	149000
Chemical Formula	C6488H10034N1746O2038S50
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	Tixagevimab has a half-life of 87.9 ± 13.9 days.[L39411]
Description	SARS-CoV-2, the causative agent of COVID-19, enters cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Blocking the interaction between the receptor-binding domain (RBD) of the S1 subunit and ACE2 inhibits viral host cell entry; animal studies indicate that antibodies capable of blocking this interaction reduce viral load and improve clinical symptoms of infection.[A243356, A243361] Tixagevimab (formerly AZD8895) is a recombinant monoclonal antibody produced in Chinese hamster ovary (CHO) cells derived from a neutralizing antibody isolated from a patient with a natural history of SARS-CoV-2 infection and modified through targeted amino acid substitutions to exhibit an extended (~85-day) half-life.[A243351, A243356, L39411] As the RBD binding site of tixagevimab does not overlap with that of [cilgavimab], the two can be administered to synergistically impair SARS-CoV-2 infection in individuals who may be exposed to the virus.[A243351, A243361, L39411] Tixagevimab is not approved for any indication by the FDA. Tixagevimab, in combination with [cilgavimab], was issued an FDA emergency use authorization (EUA) on December 9, 2021, for the pre-exposure prophylaxis of COVID-19 in individuals at increased risk for whom vaccination is not recommended. The combination is co-packaged and available under the name EVUSHELD (formerly AZD7442).[L39411]
Indication/Disease	Tixagevimab has been issued an emergency use authorization (EUA) by the FDA, in combination with [cilgavimab], for the pre-exposure prophylaxis of COVID-19 in adult and pediatric patients aged 12 years and older weighing at least 40 kg. Furthermore, patients must not be currently infected with SARS-CoV-2 or have had known exposure to an individual infected with SARS-CoV-2 and must either be immunocompromised due to a medical condition, medication, or treatment or be otherwise ineligible for vaccination with any eligible COVID-19 vaccine due to a history of severe adverse reactions.[L39411] The combination of tixagevimab and [cilgavimab] is not authorized for the treatment or post-exposure prophylaxis of COVID-19 and is not a substitute for COVID-19 vaccination. Individuals receiving therapy following COVID-19 vaccination should wait at least two weeks.[L39411]
Pharmacodynamics	Tixagevimab is an extended half-life recombinant human IgG1 monoclonal antibody directed against the SARS-CoV-2 spike (S) protein. Administered concurrently with [cilgavimab], the combination carries a risk of hypersensitivity reactions and requires caution when administering to patients with thrombocytopenia or a coagulation disorder. Based on limited clinical experience, caution should also be exercised in patients with cardiac risk factors or a history of cardiovascular disease. As there is limited experience with this combination, unexpected serious adverse events may occur.[L39411]
Mechanism of Action	SARS-CoV-2, the causative agent of COVID-19, enters cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Of the two subunits comprising the trimeric S glycoprotein, the S1 subunit binds ACE2 via its receptor-binding domain (RBD) while the central S2 subunit mediates fusion following S1 shedding.[A243351, A243356] Large-scale screens suggest that the most potently neutralizing antibodies recovered from the B cells of those convalescing following natural infection with SARS-CoV-2 bind to the RBD of S1 and are capable of disrupting the interaction between the RBD and human ACE2.[A243356] Tixagevimab (AZD8895)is a recombinant human IgG1 monoclonal antibody based on a neutralizing antibody (COV2-2196) isolated from patients with a natural history of SARS-CoV-2 infection and modified through specific amino acid substitutions to extend its half-life and reduce antibody effector functions.[L39411] Tixagevimab binds to a non-overlapping region of the S1 RBD as [cilgavimab] but is only capable of binding the S protein in its "up" conformation (K_D of 2.76 pM).[A243356, A243361, L39411] Cell culture studies suggest little to no antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), or antibody-dependent natural killer cell activation (ADNKA), suggesting the protective effect is due solely to inhibition of the RBD-ACE2 interaction. Tixagevimab inhibits RBD-ACE2 binding with an IC₅₀ of 0.32 nM (48 ng/mL) and neutralizes SARS-CoV-2 (strain USA-WA1/2020) in a cellular assay with an EC₅₀ value of 60.7 pM (9 ng/mL).[L39411] As with other antiviral treatments, there is a risk of resistant variants emerging during treatment. Experiments to identify escape variants during culture of recombinant vesicular stomatitis virus expressing the S protein (VSV-SARS-CoV-2) or authentic SARS-CoV-2 (strain USA-WA1/2020) identified K444E, K444R, and R346I as potential single-nucleotide escape variants for [cilgavimab] (conferring a >200-fold reduction in susceptibility). However, no escape variants were identified to tixagevimab or the combination of [cilgavimab] and tixagevimab.[A243361, L39411]
Toxicity	Toxicity information regarding tixagevimab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects. Symptomatic and supportive measures are recommended.[L39411]
Metabolism	As a monoclonal antibody, tixagevimab is expected to undergo proteolytic degradation.[L39411]
Absorption	A single 150 mg intramuscular dose of tixagevimab, given concurrently with 150 mg of [cilgavimab], resulted in a C_max geometric mean (%CV) of 16.5 (35.6) µg/mL in a median T_max of 14.0 (range 3.1-30) days. The observed geometric mean (%CV) one, 150, or 210 days following dosing was 4.4 (92.2), 6.6 (25.6), and 4.0 (31.6) µg/mL. This single dose resulted in an AUC_0-8 of 2529 (30.2) µg
	Tixagevimab has an apparent volume of distribution of 7.7 ± 1.97 L.[L39411]
Clearance	Tixagevimab has an apparent clearance of 0.062 ± 0.019 L/day.[L39411]
Categories	Immunoglobulins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Spike glycoprotein
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	16069
Therapeutic ID	Th1670
Protein Name	Tixagevimab
Sequence	NA
Molecular Weight	149000
Chemical Formula	C6488H10034N1746O2038S50
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	Tixagevimab has a half-life of 87.9 ± 13.9 days.[L39411]
Description	SARS-CoV-2, the causative agent of COVID-19, enters cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Blocking the interaction between the receptor-binding domain (RBD) of the S1 subunit and ACE2 inhibits viral host cell entry; animal studies indicate that antibodies capable of blocking this interaction reduce viral load and improve clinical symptoms of infection.[A243356, A243361] Tixagevimab (formerly AZD8895) is a recombinant monoclonal antibody produced in Chinese hamster ovary (CHO) cells derived from a neutralizing antibody isolated from a patient with a natural history of SARS-CoV-2 infection and modified through targeted amino acid substitutions to exhibit an extended (~85-day) half-life.[A243351, A243356, L39411] As the RBD binding site of tixagevimab does not overlap with that of [cilgavimab], the two can be administered to synergistically impair SARS-CoV-2 infection in individuals who may be exposed to the virus.[A243351, A243361, L39411] Tixagevimab is not approved for any indication by the FDA. Tixagevimab, in combination with [cilgavimab], was issued an FDA emergency use authorization (EUA) on December 9, 2021, for the pre-exposure prophylaxis of COVID-19 in individuals at increased risk for whom vaccination is not recommended. The combination is co-packaged and available under the name EVUSHELD (formerly AZD7442).[L39411]
Indication/Disease	Tixagevimab has been issued an emergency use authorization (EUA) by the FDA, in combination with [cilgavimab], for the pre-exposure prophylaxis of COVID-19 in adult and pediatric patients aged 12 years and older weighing at least 40 kg. Furthermore, patients must not be currently infected with SARS-CoV-2 or have had known exposure to an individual infected with SARS-CoV-2 and must either be immunocompromised due to a medical condition, medication, or treatment or be otherwise ineligible for vaccination with any eligible COVID-19 vaccine due to a history of severe adverse reactions.[L39411] The combination of tixagevimab and [cilgavimab] is not authorized for the treatment or post-exposure prophylaxis of COVID-19 and is not a substitute for COVID-19 vaccination. Individuals receiving therapy following COVID-19 vaccination should wait at least two weeks.[L39411]
Pharmacodynamics	Tixagevimab is an extended half-life recombinant human IgG1 monoclonal antibody directed against the SARS-CoV-2 spike (S) protein. Administered concurrently with [cilgavimab], the combination carries a risk of hypersensitivity reactions and requires caution when administering to patients with thrombocytopenia or a coagulation disorder. Based on limited clinical experience, caution should also be exercised in patients with cardiac risk factors or a history of cardiovascular disease. As there is limited experience with this combination, unexpected serious adverse events may occur.[L39411]
Mechanism of Action	SARS-CoV-2, the causative agent of COVID-19, enters cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Of the two subunits comprising the trimeric S glycoprotein, the S1 subunit binds ACE2 via its receptor-binding domain (RBD) while the central S2 subunit mediates fusion following S1 shedding.[A243351, A243356] Large-scale screens suggest that the most potently neutralizing antibodies recovered from the B cells of those convalescing following natural infection with SARS-CoV-2 bind to the RBD of S1 and are capable of disrupting the interaction between the RBD and human ACE2.[A243356] Tixagevimab (AZD8895)is a recombinant human IgG1 monoclonal antibody based on a neutralizing antibody (COV2-2196) isolated from patients with a natural history of SARS-CoV-2 infection and modified through specific amino acid substitutions to extend its half-life and reduce antibody effector functions.[L39411] Tixagevimab binds to a non-overlapping region of the S1 RBD as [cilgavimab] but is only capable of binding the S protein in its "up" conformation (K_D of 2.76 pM).[A243356, A243361, L39411] Cell culture studies suggest little to no antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), or antibody-dependent natural killer cell activation (ADNKA), suggesting the protective effect is due solely to inhibition of the RBD-ACE2 interaction. Tixagevimab inhibits RBD-ACE2 binding with an IC₅₀ of 0.32 nM (48 ng/mL) and neutralizes SARS-CoV-2 (strain USA-WA1/2020) in a cellular assay with an EC₅₀ value of 60.7 pM (9 ng/mL).[L39411] As with other antiviral treatments, there is a risk of resistant variants emerging during treatment. Experiments to identify escape variants during culture of recombinant vesicular stomatitis virus expressing the S protein (VSV-SARS-CoV-2) or authentic SARS-CoV-2 (strain USA-WA1/2020) identified K444E, K444R, and R346I as potential single-nucleotide escape variants for [cilgavimab] (conferring a >200-fold reduction in susceptibility). However, no escape variants were identified to tixagevimab or the combination of [cilgavimab] and tixagevimab.[A243361, L39411]
Toxicity	Toxicity information regarding tixagevimab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects. Symptomatic and supportive measures are recommended.[L39411]
Metabolism	As a monoclonal antibody, tixagevimab is expected to undergo proteolytic degradation.[L39411]
Absorption	A single 150 mg intramuscular dose of tixagevimab, given concurrently with 150 mg of [cilgavimab], resulted in a C_max geometric mean (%CV) of 16.5 (35.6) µg/mL in a median T_max of 14.0 (range 3.1-30) days. The observed geometric mean (%CV) one, 150, or 210 days following dosing was 4.4 (92.2), 6.6 (25.6), and 4.0 (31.6) µg/mL. This single dose resulted in an AUC_0-8 of 2529 (30.2) µg
	Tixagevimab has an apparent volume of distribution of 7.7 ± 1.97 L.[L39411]
Clearance	Tixagevimab has an apparent clearance of 0.062 ± 0.019 L/day.[L39411]
Categories	Proteins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Spike glycoprotein
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	16070
Therapeutic ID	Th1670
Protein Name	Tixagevimab
Sequence	NA
Molecular Weight	149000
Chemical Formula	C6488H10034N1746O2038S50
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
Half-life	Tixagevimab has a half-life of 87.9 ± 13.9 days.[L39411]
Description	SARS-CoV-2, the causative agent of COVID-19, enters cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Blocking the interaction between the receptor-binding domain (RBD) of the S1 subunit and ACE2 inhibits viral host cell entry; animal studies indicate that antibodies capable of blocking this interaction reduce viral load and improve clinical symptoms of infection.[A243356, A243361] Tixagevimab (formerly AZD8895) is a recombinant monoclonal antibody produced in Chinese hamster ovary (CHO) cells derived from a neutralizing antibody isolated from a patient with a natural history of SARS-CoV-2 infection and modified through targeted amino acid substitutions to exhibit an extended (~85-day) half-life.[A243351, A243356, L39411] As the RBD binding site of tixagevimab does not overlap with that of [cilgavimab], the two can be administered to synergistically impair SARS-CoV-2 infection in individuals who may be exposed to the virus.[A243351, A243361, L39411] Tixagevimab is not approved for any indication by the FDA. Tixagevimab, in combination with [cilgavimab], was issued an FDA emergency use authorization (EUA) on December 9, 2021, for the pre-exposure prophylaxis of COVID-19 in individuals at increased risk for whom vaccination is not recommended. The combination is co-packaged and available under the name EVUSHELD (formerly AZD7442).[L39411]
Indication/Disease	Tixagevimab has been issued an emergency use authorization (EUA) by the FDA, in combination with [cilgavimab], for the pre-exposure prophylaxis of COVID-19 in adult and pediatric patients aged 12 years and older weighing at least 40 kg. Furthermore, patients must not be currently infected with SARS-CoV-2 or have had known exposure to an individual infected with SARS-CoV-2 and must either be immunocompromised due to a medical condition, medication, or treatment or be otherwise ineligible for vaccination with any eligible COVID-19 vaccine due to a history of severe adverse reactions.[L39411] The combination of tixagevimab and [cilgavimab] is not authorized for the treatment or post-exposure prophylaxis of COVID-19 and is not a substitute for COVID-19 vaccination. Individuals receiving therapy following COVID-19 vaccination should wait at least two weeks.[L39411]
Pharmacodynamics	Tixagevimab is an extended half-life recombinant human IgG1 monoclonal antibody directed against the SARS-CoV-2 spike (S) protein. Administered concurrently with [cilgavimab], the combination carries a risk of hypersensitivity reactions and requires caution when administering to patients with thrombocytopenia or a coagulation disorder. Based on limited clinical experience, caution should also be exercised in patients with cardiac risk factors or a history of cardiovascular disease. As there is limited experience with this combination, unexpected serious adverse events may occur.[L39411]
Mechanism of Action	SARS-CoV-2, the causative agent of COVID-19, enters cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Of the two subunits comprising the trimeric S glycoprotein, the S1 subunit binds ACE2 via its receptor-binding domain (RBD) while the central S2 subunit mediates fusion following S1 shedding.[A243351, A243356] Large-scale screens suggest that the most potently neutralizing antibodies recovered from the B cells of those convalescing following natural infection with SARS-CoV-2 bind to the RBD of S1 and are capable of disrupting the interaction between the RBD and human ACE2.[A243356] Tixagevimab (AZD8895)is a recombinant human IgG1 monoclonal antibody based on a neutralizing antibody (COV2-2196) isolated from patients with a natural history of SARS-CoV-2 infection and modified through specific amino acid substitutions to extend its half-life and reduce antibody effector functions.[L39411] Tixagevimab binds to a non-overlapping region of the S1 RBD as [cilgavimab] but is only capable of binding the S protein in its "up" conformation (K_D of 2.76 pM).[A243356, A243361, L39411] Cell culture studies suggest little to no antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), or antibody-dependent natural killer cell activation (ADNKA), suggesting the protective effect is due solely to inhibition of the RBD-ACE2 interaction. Tixagevimab inhibits RBD-ACE2 binding with an IC₅₀ of 0.32 nM (48 ng/mL) and neutralizes SARS-CoV-2 (strain USA-WA1/2020) in a cellular assay with an EC₅₀ value of 60.7 pM (9 ng/mL).[L39411] As with other antiviral treatments, there is a risk of resistant variants emerging during treatment. Experiments to identify escape variants during culture of recombinant vesicular stomatitis virus expressing the S protein (VSV-SARS-CoV-2) or authentic SARS-CoV-2 (strain USA-WA1/2020) identified K444E, K444R, and R346I as potential single-nucleotide escape variants for [cilgavimab] (conferring a >200-fold reduction in susceptibility). However, no escape variants were identified to tixagevimab or the combination of [cilgavimab] and tixagevimab.[A243361, L39411]
Toxicity	Toxicity information regarding tixagevimab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects. Symptomatic and supportive measures are recommended.[L39411]
Metabolism	As a monoclonal antibody, tixagevimab is expected to undergo proteolytic degradation.[L39411]
Absorption	A single 150 mg intramuscular dose of tixagevimab, given concurrently with 150 mg of [cilgavimab], resulted in a C_max geometric mean (%CV) of 16.5 (35.6) µg/mL in a median T_max of 14.0 (range 3.1-30) days. The observed geometric mean (%CV) one, 150, or 210 days following dosing was 4.4 (92.2), 6.6 (25.6), and 4.0 (31.6) µg/mL. This single dose resulted in an AUC_0-8 of 2529 (30.2) µg
	Tixagevimab has an apparent volume of distribution of 7.7 ± 1.97 L.[L39411]
Clearance	Tixagevimab has an apparent clearance of 0.062 ± 0.019 L/day.[L39411]
Categories	Serum Globulins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Spike glycoprotein
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