Overview
Eosinophils are involved in inflammatory immune responses, and prolonged hypereosinophilia (typically defined as absolute eosinophil levels of 1500/mm or more) is associated with a spectrum of diseases, including severe asthma, eosinophilic granulomatosis with polyangiitis (EGPA), and hypereosinophilic syndrome (HES). The pathogenesis of eosinophilia is complex, but IL-5 is recognized as a key cytokine involved in the differentiation, recruitment, activation, and prolonged survival of eosinophils in peripheral tissue. Activated eosinophils further stimulate an inflammatory response and also induce tissue lesions and promote fibrosis, all of which contribute to the multifactorial symptomatology of hypereosinophilic diseases. Mepolizumab is a fully-humanized recombinant IgG1 kappa monoclonal antibody directed against IL-5 produced in Chinese hamster ovary cells. Mepolizumab was first approved by the FDA on November 4, 2015, as an add-on therapy for severe asthma and marketed under the brand name Nucala by GlaxoSmithKline. This indication was subsequently expanded to cover EGPA on December 12, 2017, and HES on September 25, 2020.
Background
Eosinophils are involved in inflammatory immune responses, and prolonged hypereosinophilia (typically defined as absolute eosinophil levels of 1500/mm or more) is associated with a spectrum of diseases, including severe asthma, eosinophilic granulomatosis with polyangiitis (EGPA), and hypereosinophilic syndrome (HES). The pathogenesis of eosinophilia is complex, but IL-5 is recognized as a key cytokine involved in the differentiation, recruitment, activation, and prolonged survival of eosinophils in peripheral tissue. Activated eosinophils further stimulate an inflammatory response and also induce tissue lesions and promote fibrosis, all of which contribute to the multifactorial symptomatology of hypereosinophilic diseases. Mepolizumab is a fully-humanized recombinant IgG1 kappa monoclonal antibody directed against IL-5 produced in Chinese hamster ovary cells. Mepolizumab was first approved by the FDA on November 4, 2015, as an add-on therapy for severe asthma and marketed under the brand name Nucala by GlaxoSmithKline. This indication was subsequently expanded to cover EGPA on December 12, 2017, and HES on September 25, 2020.
Indication
Mepolizumab is an anti-IL-5 IgG1 kappa monoclonal antibody indicated as an add-on maintenance treatment in patients aged six years and older with severe eosinophilic asthma and as a treatment in adult patients for eosinophilic granulomatosis with polyangiitis (EGPA). Mepolizumab is also indicated for the treatment of hypereosinophilic syndrome (HES) in patients aged 12 and older in whom eosinophilia is present for at least six months without an identifiable non-hematologic secondary cause. Mepolizumab is additionally indicated as an add-on maintenance treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) in patients ≥18 years old with inadequate response to nasal corticosteroids.
Associated Conditions
- Chronic Rhinosinusitis Phenotype With Nasal Polyps (CRSwNP)
- Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss) (EGPA)
- Hypereosinophilic Syndrome (HES)
- Severe Eosinophilic Asthma
Clinical Trials
Title | Posted | Study ID | Phase | Status | Sponsor |
|---|---|---|---|---|---|
2024/11/11 | N/A | Recruiting | |||
2024/08/27 | Phase 2 | Recruiting | Xijing Hospital | ||
2024/04/04 | N/A | Completed | |||
2024/02/14 | N/A | Not yet recruiting | |||
2023/10/30 | Phase 4 | Not yet recruiting | |||
2023/10/05 | N/A | Recruiting | |||
2023/09/18 | Phase 4 | Active, not recruiting | |||
2023/07/12 | Phase 4 | Active, not recruiting | |||
2023/06/28 | Phase 4 | Not yet recruiting | Instituto de Investigación Marqués de Valdecilla | ||
2023/06/15 | Phase 4 | Recruiting | Centre hospitalier de l'Université de Montréal (CHUM) |
FDA Drug Approvals
Approved Product | Manufacturer | NDC Code | Route | Strength | Effective Date |
|---|---|---|---|---|---|
| GlaxoSmithKline LLC | 0173-0881 | SUBCUTANEOUS | 100 mg in 1 mL | 1/22/2022 | |
| GlaxoSmithKline LLC | 0173-0892 | SUBCUTANEOUS | 100 mg in 1 mL | 1/22/2022 | |
| GlaxoSmithKline LLC | 0173-0904 | SUBCUTANEOUS | 40 mg in 0.4 mL | 1/22/2022 |
EMA Drug Approvals
Approved Product | Authorization Holder | Status | Issued Date |
|---|---|---|---|
Authorised | 12/1/2015 | ||
Authorised | 12/1/2015 |
HSA Drug Approvals
Approved Product | Manufacturer | Approval Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| NUCALA SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE 40MG/0.4ML | SIN16811P | INJECTION, SOLUTION | 40mg/0.4ml | 6/19/2023 | |
| NUCALA POWDER FOR SOLUTION FOR INJECTION 100mg | SIN15396P | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION | 100mg/vial | 12/14/2017 | |
| NUCALA SOLUTION FOR INJECTION IN PRE-FILLED PEN 100MG/ML | SIN16172P | INJECTION, SOLUTION | 100mg/ml | 4/27/2021 | |
| NUCALA SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE 100MG/ML | SIN16171P | INJECTION, SOLUTION | 100mg/ml | 4/27/2021 |
NMPA Drug Approvals
Approved Product | Company | Approval Number | Drug Type | Dosage Form | Approval Date |
|---|---|---|---|---|---|
| Mepolizumab Injection | 国药准字SJ20210029 | 生物制品 | 注射剂 | 11/17/2021 | |
| Mepolizumab Injection | 国药准字SJ20210030 | 生物制品 | 注射剂 | 11/17/2021 |
PPB Drug Approvals
Approved Product | Registration No. | Company | Licence No. | Strength | Registration Date |
|---|---|---|---|---|---|
| NUCALA SOLUTION FOR INJECTION IN PRE-FILLED PEN 100MG/1ML | N/A | N/A | N/A | 9/29/2020 | |
| NUCALA POWDER FOR SOLUTION FOR INJECTION 100 MG | N/A | N/A | N/A | 3/29/2017 |
TGA Drug Approvals
Approved Product | ARTG ID | Sponsor | Registration Type | Status | Registration Date |
|---|---|---|---|---|---|
| NUCALA mepolizumab 100 mg solution for injection in pre-filled pen | 317304 | Medicine | A | 12/2/2019 | |
| NUCALA mepolizumab 100 mg powder for injection | 232028 | Medicine | A | 2/2/2016 | |
| NUCALA mepolizumab 100 mg solution for injection in pre-filled syringe | 312652 | Medicine | A | 12/2/2019 |