Detailed description page of THPdb

Details of Th1210 which contains 1 entries.

Entry 1
(1) Primary information
ID 1819
ThPP ID Th1210
Therapeutic Peptide/Protein Name Mepolizumab
Sequence NA view full sequnce in fasta
Functional Classification Ib
Molecular Weight 149000
Chemical Formula
Isoelectric Point NA
Hydrophobicity NA
Melting Point (℃) NA
Half Life 16 to 22 days.
Description Mepolizumab is a humanized IL-5 antagonist monoclonal antibody produced by recombinant DNA technology in Chinese hamster ovary cells. It has a molecular weight of approximately 149 kDa. It was approved by the FDA in November, 2015 for the treatment of asthma under the brand name Nucala (marketed by GlaxoSmithKline). Mepolizumab has been investigated in the treatment of severe nasal polyposis, among numerous other conditions.
Indication/Disease Mepolizumab is indicated for add-on maintenance treatment of severe eosinophilic asthma, as identified by blood eosinophils greater than or equal to 150 cells/Î¼l at initiation of treatment or blood eosinophils greater than or equal to 300 cells/Î¼l in the past 12 months, in patients aged 12 years and older. Mepolizumab has been shown to reduce exacerbations of asthma in patients with an exacerbation history
Pharmacodynamics The pharmacodynamic response (blood eosinophil reduction) following repeat doses of mepolizumab administered subcutaneously or intravenously was evaluated in subjects with asthma and blood eosinophil levels greater than 200 cells/mcL. Subjects received 1 of 4 mepolizumab treatments (administered every 28 days for a total of 3 doses): 12.5 mg SC, 125 mg SC, 250 mg SC, or 75 mg IV. Sixty-six (66) of the 70 randomized subjects completed the trial. Compared with baseline levels, blood eosinophils decreased in a dose-dependent manner. A reduction in blood eosinophil levels was observed in all treatment groups by Day 3. On Day 84 (4 weeks post-last dose), the observed geometric mean reduction from baseline in blood eosinophils was 64%, 78%, 84%, and 90% in the 12.5-mg SC, 75-mg IV, 125-mg SC, and 250-mg SC treatment groups, respectively. The model-predicted SC doses providing 50% and 90% of maximal reduction of blood eosinophils at Day 84 were estimated to be 11 and 99 mg, respectively. These results, along with the clinical efficacy data from the dose-ranging exacerbation trial (Trial 1) supported the evaluation of mepolizumab 75 mg IV and 100 mg SC in the confirmatory trials [see Clinical Studies (14)]. Following SC administration of mepolizumab 100 mg every 4 weeks for 32 weeks (Trial 2), blood eosinophils were reduced to a geometric mean count of 40 cells/mcL, which corresponds to a geometric mean reduction of 84% compared with placebo. This magnitude of reduction was observed within 4 weeks of treatment and was maintained throughout the treatment period
Mechanism of Action Mepolizumab is an interleukin-5 antagonist (IgG1 kappa). IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils. Mepolizumab binds to IL-5 with a dissociation constant of 100 pM, inhibiting the bioactivity of IL-5 by blocking its binding to the alpha chain of the IL-5 receptor complex expressed on the eosinophil cell surface. Inflammation is an important component in the pathogenesis of asthma. Multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) are involved in inflammation. Mepolizumab, by inhibiting IL-5 signaling, reduces the production and survival of eosinophils; however, the mechanism of mepolizumab action in asthma has not been definitively established.
Toxicity
Metabolism Mepolizumab is a humanized IgG1 monoclonal antibody that is degraded by proteolytic enzymes widely distributed in the body and not restricted to hepatic tissue.
Absorption Following 100-mg SC administration in the upper arm of subjects with asthma, the bioavailability of mepolizumab was estimated to be approximately 80%. Following repeat SC administration once every 4 weeks, there was approximately a 2-fold accumulation at steady state.
Volume of Distribution The population central volume of distribution of mepolizumab in patients with asthma is estimated to be 3.6 L for a 70-kg individual.
Clearance The population apparent systemic clearance of mepolizumab in patients with asthma is estimated to be 0.28 L/day for a 70-kg individual.
Categories Antineoplastic and Immunomodulating Agents, Immunosuppressive Agents, Interleukin Inhibitors
Patents Number US2008134721
Date of Issue 39202
Date of Expiry 46507
Drug Interaction
Target Interleukin-5
Information of corresponding available drug in the market
Brand Name Nucala
Company Glaxosmithkline Inc
Brand Discription NUCALA is supplied as a sterile, white to off-white, preservative-free, lyophilized powder for subcutaneous injection after reconstitution. Upon reconstitution with 1.2 mL of Sterile Water for Injection, USP
Prescribed for NUCALAÂ® is indicated for the add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype.
Chemical Name NA
Formulation 100 mg/mL
Physcial Appearance lyophilized powder
Route of Administration subcutaneous
Recommended Dosage The recommended dose of NUCALA is 100 mg administered once every 4 weeks by subcutaneous injection into the upper arm, thigh, or abdomen.
Contraindication NUCALA should not be administered to patients with a history of hypersensitivity to mepolizumab or excipients in the formulation.
Side Effects Hypersensitivity reactions; Opportunistic infections: herpes zoster
Useful Link http://www.rxlist.com/nucala-drug/side-effects-interactions.htm
PubMed ID 15071612, 28319473, 28281440, 28279664, 28137490, 28085503, 27942351, 27931289, 27906698
3-D Structure N.A.

OSDDlinux

Raghava's Group

IMTECH

CSIR

CRDD
CPPSITE 2.0

(1) Primary information
Entry 1
ID	1819
ThPP ID	Th1210
Therapeutic Peptide/Protein Name	Mepolizumab
Sequence	NA view full sequnce in fasta
Functional Classification	Ib
Molecular Weight	149000
Chemical Formula
Isoelectric Point	NA
Hydrophobicity	NA
Melting Point (℃)	NA
Half Life	16 to 22 days.
Description	Mepolizumab is a humanized IL-5 antagonist monoclonal antibody produced by recombinant DNA technology in Chinese hamster ovary cells. It has a molecular weight of approximately 149 kDa. It was approved by the FDA in November, 2015 for the treatment of asthma under the brand name Nucala (marketed by GlaxoSmithKline). Mepolizumab has been investigated in the treatment of severe nasal polyposis, among numerous other conditions.
Indication/Disease	Mepolizumab is indicated for add-on maintenance treatment of severe eosinophilic asthma, as identified by blood eosinophils greater than or equal to 150 cells/Î¼l at initiation of treatment or blood eosinophils greater than or equal to 300 cells/Î¼l in the past 12 months, in patients aged 12 years and older. Mepolizumab has been shown to reduce exacerbations of asthma in patients with an exacerbation history
Pharmacodynamics	The pharmacodynamic response (blood eosinophil reduction) following repeat doses of mepolizumab administered subcutaneously or intravenously was evaluated in subjects with asthma and blood eosinophil levels greater than 200 cells/mcL. Subjects received 1 of 4 mepolizumab treatments (administered every 28 days for a total of 3 doses): 12.5 mg SC, 125 mg SC, 250 mg SC, or 75 mg IV. Sixty-six (66) of the 70 randomized subjects completed the trial. Compared with baseline levels, blood eosinophils decreased in a dose-dependent manner. A reduction in blood eosinophil levels was observed in all treatment groups by Day 3. On Day 84 (4 weeks post-last dose), the observed geometric mean reduction from baseline in blood eosinophils was 64%, 78%, 84%, and 90% in the 12.5-mg SC, 75-mg IV, 125-mg SC, and 250-mg SC treatment groups, respectively. The model-predicted SC doses providing 50% and 90% of maximal reduction of blood eosinophils at Day 84 were estimated to be 11 and 99 mg, respectively. These results, along with the clinical efficacy data from the dose-ranging exacerbation trial (Trial 1) supported the evaluation of mepolizumab 75 mg IV and 100 mg SC in the confirmatory trials [see Clinical Studies (14)]. Following SC administration of mepolizumab 100 mg every 4 weeks for 32 weeks (Trial 2), blood eosinophils were reduced to a geometric mean count of 40 cells/mcL, which corresponds to a geometric mean reduction of 84% compared with placebo. This magnitude of reduction was observed within 4 weeks of treatment and was maintained throughout the treatment period
Mechanism of Action	Mepolizumab is an interleukin-5 antagonist (IgG1 kappa). IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils. Mepolizumab binds to IL-5 with a dissociation constant of 100 pM, inhibiting the bioactivity of IL-5 by blocking its binding to the alpha chain of the IL-5 receptor complex expressed on the eosinophil cell surface. Inflammation is an important component in the pathogenesis of asthma. Multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) are involved in inflammation. Mepolizumab, by inhibiting IL-5 signaling, reduces the production and survival of eosinophils; however, the mechanism of mepolizumab action in asthma has not been definitively established.
Toxicity
Metabolism	Mepolizumab is a humanized IgG1 monoclonal antibody that is degraded by proteolytic enzymes widely distributed in the body and not restricted to hepatic tissue.
Absorption	Following 100-mg SC administration in the upper arm of subjects with asthma, the bioavailability of mepolizumab was estimated to be approximately 80%. Following repeat SC administration once every 4 weeks, there was approximately a 2-fold accumulation at steady state.
Volume of Distribution	The population central volume of distribution of mepolizumab in patients with asthma is estimated to be 3.6 L for a 70-kg individual.
Clearance	The population apparent systemic clearance of mepolizumab in patients with asthma is estimated to be 0.28 L/day for a 70-kg individual.
Categories	Antineoplastic and Immunomodulating Agents, Immunosuppressive Agents, Interleukin Inhibitors
Patents Number	US2008134721
Date of Issue	39202
Date of Expiry	46507
Drug Interaction
Target	Interleukin-5
Information of corresponding available drug in the market
Brand Name	Nucala
Company	Glaxosmithkline Inc
Brand Discription	NUCALA is supplied as a sterile, white to off-white, preservative-free, lyophilized powder for subcutaneous injection after reconstitution. Upon reconstitution with 1.2 mL of Sterile Water for Injection, USP
Prescribed for	NUCALAÂ® is indicated for the add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype.
Chemical Name	NA
Formulation	100 mg/mL
Physcial Appearance	lyophilized powder
Route of Administration	subcutaneous
Recommended Dosage	The recommended dose of NUCALA is 100 mg administered once every 4 weeks by subcutaneous injection into the upper arm, thigh, or abdomen.
Contraindication	NUCALA should not be administered to patients with a history of hypersensitivity to mepolizumab or excipients in the formulation.
Side Effects	Hypersensitivity reactions; Opportunistic infections: herpes zoster
Useful Link	http://www.rxlist.com/nucala-drug/side-effects-interactions.htm
PubMed ID	15071612, 28319473, 28281440, 28279664, 28137490, 28085503, 27942351, 27931289, 27906698
3-D Structure	N.A.