Depemokimab Late-Breaking Data Shows 54% Reduction in Severe Asthma Attacks at ERS
New data from the SWIFT-1 and SWIFT-2 phase III clinical trials reveal that GSK's ultra-long-acting biologic, depemokimab, significantly reduced severe asthma exacerbations by 54% over 52 weeks compared to a placebo, when combined with standard care.
Depemokimab, which is administered every six months, demonstrated prolonged suppression of a key marker linked to type 2 inflammation, a major contributor to asthma attacks and hospitalizations. The trials assessed its effectiveness and safety in patients with severe asthma characterized by elevated eosinophil levels, a type of white blood cell associated with inflammation.
SWIFT-1 and SWIFT-2 Trial Results
The SWIFT-1 and SWIFT-2 studies were identical in design, with the same primary and secondary objectives.
Both trials met their primary goal, showing statistically significant reductions in the annual rate of asthma exacerbations over 52 weeks compared to placebo.
Pooled analysis of the two trials showed a 54% reduction in exacerbations, with secondary results indicating a 72% decrease in the rate of hospitalizations or emergency department visits due to severe asthma attacks.
While the pooled results of the secondary endpoints were not adjusted for multiple comparisons, and thus are considered nominally significant, improvements in quality of life and symptom-based measurements in the individual trials did not reach statistical significance.
Implications for Asthma Treatment
These results align with GSK's ongoing efforts to advance treatments for severe asthma, particularly by reducing exacerbations that can lead to hospitalizations and long-term lung damage. Sustained suppression of type 2 inflammation through long-acting treatments like depemokimab could potentially alter the progression of asthma and help patients manage the condition with fewer medical visits.
Depemokimab is the first ultra-long-acting biologic to be tested in phase III trials for asthma. It specifically targets interleukin-5 (IL-5), a protein that plays a key role in type 2 inflammation. Over 80% of people with severe asthma have this type of inflammation, often characterized by elevated eosinophil levels. Identifying these patients can help healthcare providers choose treatments that more effectively prevent exacerbations.
Safety Profile and Adverse Events
The safety profile of depemokimab was comparable to the placebo in both trials. In SWIFT-1, adverse events were reported by 73% of participants in both the depemokimab and placebo groups, while in SWIFT-2, 72% of depemokimab-treated patients experienced adverse events compared to 78% in the placebo group. No deaths or serious adverse events were found to be linked to the treatment.
Depemokimab Development Program
The phase III development of depemokimab includes the SWIFT-1 and SWIFT-2 trials for severe asthma, alongside an open-label extension study known as AGILE. SWIFT-1 and SWIFT-2 were randomized, double-blind, placebo-controlled trials conducted across multiple centers over 52 weeks. The trials enrolled 382 and 380 participants, respectively, who received either depemokimab or placebo in addition to standard asthma treatments, which included medium-to-high dose inhaled corticosteroids and at least one additional controller.
In the individual studies, depemokimab demonstrated a 58% reduction in exacerbations in SWIFT-1 and a 48% reduction in SWIFT-2 compared to placebo. Additionally, GSK is conducting the NIMBLE study to assess the safety and efficacy of switching patients from other biologics, like mepolizumab or benralizumab, to depemokimab.
Depemokimab’s Potential Beyond Asthma
With a long half-life and strong affinity for IL-5, depemokimab offers sustained inhibition of inflammatory functions and is being investigated for its potential in treating a variety of other type 2 inflammatory diseases.
Ongoing phase III trials are exploring its use in conditions such as eosinophilic granulomatosis with polyangiitis (EGPA), chronic rhinosinusitis with nasal polyps (CRSwNP), and hypereosinophilic syndrome (HES).
Understanding Severe Asthma and Type 2 Inflammation
Severe asthma is a chronic condition that requires treatment with high-dose inhaled corticosteroids combined with a second controller or biologic therapy. Despite treatment, many patients experience poor control over their symptoms, leading to frequent exacerbations, hospital visits, and lost income due to illness. Severe asthma accounts for a significant proportion of asthma-related healthcare costs globally.
Dupixent Data Highlights Significant Clinical Benefit in COPD Phase 3 Trials
Results from a combined analysis of the BOREAS and NOTUS phase 3 trials have reinforced the clinical value of Dupixent (dupilumab) in treating chronic obstructive pulmonary disease (COPD).
The data demonstrated a 31% reduction in exacerbations and improvements in lung function compared to placebo.
Pooled Analysis of Phase 3 Studies
The analysis from the BOREAS and NOTUS studies showed that Dupixent significantly reduced the frequency of exacerbations and enhanced lung function in adults suffering from uncontrolled COPD with type 2 inflammation, identified through elevated blood eosinophil levels. The European Medicines Agency (EMA) became the first regulatory body globally to approve Dupixent as an add-on therapy for adults with uncontrolled COPD. This approval is specific to individuals already on a treatment regime that includes a combination of inhaled corticosteroids (ICS), a long-acting beta2-agonist (LABA), and a long-acting muscarinic antagonist (LAMA), or for those using a LABA and LAMA when ICS is not suitable. Additionally, Dupixent has been approved in Brazil and Russia for similar patient profiles, with other regulatory submissions under review in countries like the US, China, and Japan.
The pooled analysis, supported by Regeneron, highlights the benefits of Dupixent for patients who were already receiving the highest level of standard inhaled care, with most on triple therapy. The 938 patients on Dupixent were compared to 936 on placebo, yielding the following key results:
A 31% reduction in the yearly rate of moderate or severe COPD exacerbations over 52 weeks.
An increase in lung function (pre-bronchodilator FEV1) by 147 mL compared to 64 mL in the placebo group after 12 weeks. These benefits were seen as early as two weeks into treatment and persisted for 52 weeks.
About COPD
Chronic obstructive pulmonary disease (COPD) is a serious lung condition that progressively worsens over time, causing breathing difficulties, coughing, and excessive mucus production. It is a major cause of death worldwide and significantly impacts daily activities, often leading to sleep problems, anxiety, and depression. Frequent exacerbations increase healthcare costs and can result in hospitalizations, further adding to the burden on patients and healthcare systems.
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