GSK: Depemokimab Monoclonal Antibody Reduces Asthma Attacks

1. Depemokimab was shown to reduce exacerbations in patients with severe asthma.
2. The proportions of adverse events of Depemokimab and the placebo were similar.

The Latest

The recent SWIFT-1 and SWIFT-2 phase 3A, randomized, placebo-controlled, parallel-group multi-center clinical trials conducted by GSK evaluated the efficacy and safety of depemokimab versus placebo in adults and adolescents with severe asthma with type 2 inflammation. The primary endpoint measured the reduction in clinically significant exacerbations (asthma attacks) over 52 weeks. The trial included 382 participants on depemokimab and 380 participants who were randomized to receive a placebo, in addition to their standard care of treatment with medium to high-dose inhaled corticosteroids plus at least one additional controller. The annualized rate of exacerbations was 0.46 with depemokimab and 1.11 with placebo in SWIFT-1. In SWIFT-2, this was 0.56 with depemokimab and 1.08 with the placebo. Pooled analysis showed a 72% reduction in clinically significant exacerbations that required hospitalization or an emergency department visit (one of the secondary endpoints). The proportions of adverse events were similar when comparing depemokimab and the placebo arms in the SWIFT-1 and SWIFT-2 studies. No deaths or serious adverse events were related to treatment.

Physician’s Perspective

Severe asthma is defined as asthma that requires treatment with high-dose inhaled corticosteroids plus a second controller or biologic therapy. It is thought to affect approximately 5% to 10% of the total population with asthma. Severe asthma is also associated with significant morbidity and mortality, primarily due to exacerbations that lead to hospitalizations. Furthermore, exacerbations are a cause of cumulative lung damage and disease progression. The cost per patient of severe asthma can be tenfold higher than in mild disease, accounting for more than 60% of asthma-related healthcare costs. Depemokimab is the first ultra-long-acting biologic that has shown a reduction in asthma exacerbations in this population. With a dosing schedule of only two injections per year, depemokimab could offer patients with severe asthma a sustained suppression of key inflammatory drivers and reduce the overall rate of exacerbations and hospitalizations. Extended dosing intervals could help to improve overall care for these patients by reducing frequent healthcare appointments.

Molecular Targets

Depemokimab is a monoclonal antibody that blocks human interleukin-5 (IL-5) binding to its receptor. IL-5 is a known core cytokine in type 2 inflammation that drives the underlying pathology in immune-mediated conditions. IL-5 is responsible for the growth, activity, and survival of eosinophils. In more than 80% of patients with severe asthma, their condition is driven by this type 2 inflammation, resulting in elevated levels of eosinophils. By blocking IL-5 from binding to its receptor, there will be less type 2 inflammation resulting in decreased asthma exacerbations.

Company History

GSK is a British multinational pharmaceutical and biotechnology company with a focus on respiratory medicine. The company is targeting to release a pipeline of vaccines, biologics, and inhaled medicines for diseases from asthma and COPD to refractory chronic cough or even rarer conditions like systemic sclerosis and interstitial lung disease. Depemokimab is currently being evaluated in phase III trials across a range of other IL-5-mediated diseases, including eosinophilic granulomatosis with polyangiitis, chronic rhinosinusitis with nasal polyps, and hypereosinophilic syndrome (HES).

Further Reading: https://www.gsk.com/en-gb/media/press-releases/depemokimab-late-breaking-data-presented-at-ers-show-a-54-reduction-in-severe-asthma-exacerbations/

©2024 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.