GSK's depemokimab has demonstrated significant efficacy in reducing severe asthma exacerbations, according to results from the SWIFT-1 and SWIFT-2 phase 3 clinical trials. The data, presented at the European Respiratory Society International Conference and published in The New England Journal of Medicine, indicate that depemokimab, an ultra-long-acting biologic, could offer a new treatment option for patients with severe asthma characterized by type 2 inflammation.
The SWIFT-1 and SWIFT-2 trials were randomized, double-blind, placebo-controlled studies that assessed the efficacy and safety of depemokimab in adults and adolescents with severe eosinophilic asthma. Participants had elevated eosinophil levels and a history of exacerbations despite using medium- or high-dose inhaled glucocorticoids.
The primary endpoint of both trials was the annualized rate of asthma exacerbations over 52 weeks. Secondary outcomes included changes in forced expiratory volume in 1 second (FEV1), St. George’s Respiratory Questionnaire (SGRQ) scores, and patient-reported asthma symptoms.
Key Findings from SWIFT-1 and SWIFT-2
In SWIFT-1, the annualized exacerbation rate was 0.46 (95% CI, 0.36 - 0.58) for depemokimab-treated patients compared to 1.11 (95% CI, 0.86 to 1.43) in the placebo arm, resulting in a rate ratio of 0.42 (95% CI, 0.30 to 0.59; P < .001). Similarly, in SWIFT-2, the exacerbation rate was 0.56 (95% CI, 0.44 - 0.70) for the treatment arm and 1.08 (95% CI, 0.83 - 1.41) for the placebo arm, with a rate ratio of 0.52 (95% CI, 0.36 - 0.73; P < .001).
A pre-specified pooled analysis of the two trials demonstrated a 54% reduction in exacerbations annually versus placebo. Furthermore, the data showed a 72% reduction in clinically significant exacerbations requiring hospitalization or emergency department visits compared to placebo.
Clinical Significance and Dosing
Depemokimab is designed to be administered via subcutaneous injection twice per year, a less frequent dosing schedule compared to existing biologics for severe asthma. Kaivan Khavandi, GSK’s global head of Respiratory/Immunology R&D, noted that this could be particularly beneficial for patients managing multiple therapies. "This is important as research shows that 73% of physicians believe longer dosing intervals would be beneficial to patients who are often juggling multiple therapies," Khavandi said.
Targeting Type 2 Inflammation
Severe asthma is often characterized by type 2 inflammation, with increased levels of eosinophils. Interleukin-5 (IL-5) is a key protein involved in this inflammatory pathway, supporting the function, growth, and longevity of eosinophils. Depemokimab has an enhanced binding affinity for IL-5, potentially providing sustained inhibition of this pathway.
Safety Profile
The incidence of adverse events was comparable between the depemokimab and placebo cohorts in both trials, indicating a favorable safety profile.
With approximately 200,000 people in the UK alone suffering from severe asthma, and over 80% of these cases driven by type 2 inflammation, depemokimab represents a promising advancement in asthma management. The data from the SWIFT-1 and SWIFT-2 trials will be used to support regulatory filings globally.
