New Depemokimab Data Shows 54% Reduction in Severe Asthma Exacerbations

LONDON, UK I September 09, 2024 I GSK plc (LSE/NYSE: GSK) has unveiled the comprehensive results from the SWIFT-1 and SWIFT-2 phase III clinical trials, which evaluated the efficacy and safety of depemokimab compared to placebo in adults and adolescents with severe asthma characterized by type 2 inflammation and elevated blood eosinophil levels.

The findings were shared at the European Respiratory Society International Conference in Vienna, Austria, and published in the New England Journal of Medicine.

SWIFT-1 and SWIFT-2 are twin studies with the same primary and secondary endpoints. Both studies achieved their primary goals, recording a substantial reduction in the annualized rate of clinically significant asthma attacks over 52 weeks compared to placebo. Specifically, the pooled analysis demonstrated a 54% reduction in exacerbations with depemokimab (Rate Ratio 0.46, 95% CI, 0.36 – 0.59, p<0.001), showing an annual exacerbation rate of 0.51 for depemokimab versus 1.11 for placebo.

In a pooled analysis, the secondary endpoint showed a 72% reduction (RR 0.28, 95% CI 0.13 – 0.61, p=0.002) in the rate of exacerbations necessitating hospitalization or emergency department visits with depemokimab (0.02 exacerbations per year) compared to placebo (0.09). It is important to note that as the pooled analysis did not control for multiple comparisons, results are termed nominally significant.

Although the secondary endpoints related to quality-of-life and symptom measures showed improvements, they did not achieve statistical significance compared to placebo.

GSK aims to advance treatment options for those suffering from severe asthma. Reducing exacerbations, which are a known risk for hospitalization and a cause of lung damage and disease progression, has long been a priority in asthma care. Depemokimab, with its potential for six-month dosing intervals, could address adherence challenges and frequent healthcare visits, offering sustained suppression of type 2 inflammation, which is a driver of exacerbations.

Kaivan Khavandi, SVP, Global Head of Respiratory/Immunology R&D at GSK, commented, "With a twice-yearly dosing schedule, depemokimab has the potential to be the first approved ultra-long-acting biologic. This could provide reassurance to physicians and millions of patients with severe asthma by reducing the rate of exacerbations and hospitalizations."

David Jackson, lead author of the SWIFT-1 and SWIFT-2 studies and Professor of Respiratory Medicine at King’s College London, stated, "As a physician, seeing research results that could transform severe asthma management is encouraging. Preventing exacerbations, especially those leading to hospitalizations, is crucial for improving patient outcomes and reducing healthcare pressures."

Depemokimab is the first ultra-long-acting biologic tested in phase III trials, targeting interleukin-5 (IL-5) with high binding affinity and potency, allowing for six-month dosing intervals. IL-5 is a key cytokine in type 2 inflammation, indicated by elevated blood eosinophil levels. Over 80% of severe asthma patients exhibit type 2 inflammation, and identifying these patients can help tailor treatments to reduce exacerbation risks.

The proportion of patients experiencing any adverse event (AE) was similar between the depemokimab and placebo groups in both SWIFT-1 and SWIFT-2 trials. No deaths or serious AEs were linked to the study treatment. The trials were conducted during a period of high COVID-19 prevalence, and COVID-19 was the most common AE reported across both groups. Other common AEs included nasopharyngitis, which was less frequent in the depemokimab group compared to placebo.

These findings will support regulatory filings globally. Depemokimab is not yet approved in any country.

The phase III program for depemokimab includes SWIFT-1, SWIFT-2, and an open-label extension study (AGILE). SWIFT-1 and SWIFT-2 were 52-week, randomized, double-blind, placebo-controlled, multicentre clinical trials involving 382 and 380 participants respectively, who received either depemokimab or placebo along with standard asthma treatments. An additional study, NIMBLE, is evaluating depemokimab's efficacy and safety in patients switching from other asthma biologics.

Depemokimab's half-life and potency for IL-5 suggest it could provide sustained inhibition of inflammatory functions and is being investigated for a range of type 2 inflammatory conditions. Current phase III trials are exploring its use in other IL-5 mediated diseases such as eosinophilic granulomatosis with polyangiitis, chronic rhinosinusitis with nasal polyps, and hypereosinophilic syndrome.

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