Phase III Trials Show Depemokimab Reduces Severe Asthma Exacerbations with Twice-Yearly Dosing
The high potency IL-5 inhibitor can be administered every 6 months, offering a convenient alternative to other biologic agents for appropriate patients with severe asthma.
Positive results from the phase III SWIFT-1 and SWIFT-2 trials with depemokimab demonstrated that, compared with placebo, the interleukin- (IL) 5 inhibitor significantly reduced the annualized rate of clinically significant asthma exacerbations in adults and adolescents with severe asthma over 52 weeks.
Across both studies, the safety profile was similar to placebo, with no new safety concerns identified, according to a news release from GSK. Analysis of these data is ongoing, the company said.
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Depemokimab is an ultra-long-acting biologic therapy with enhanced binding affinity and high potency for IL-5 that allows twice yearly dosing for individuals with severe asthma with type 2 inflammation characterized by elevated blood eosinophil count. IL-5 is a key cytokine in type 2 inflammation, the underlying pathology responsible for more than 80% of the severe phenotype. Type 2 inflammation can lead to unpredictable and dangerous asthma exacerbations and poor disease control despite even for individuals taking high-dose inhaled corticosteroids and other therapies.2,3,4 Current biologic treatments typically require more frequent administration, but the longer dosing interval with depemokimab offers a promising alternative for simplifying disease management, GSK said.
“These results add to the established body of evidence that targeted inhibition of IL-5 plays a key role in reducing type 2 inflammation that drives severe asthma exacerbations. Depemokimab could offer the possibility of sustained inhibition of this pathway, with a dosing schedule of just two injections per year,” Kaivan Khavandi, SVP, global head of respiratory/immunology R&D at GSK emphasized in the company news release.
In the SWIFT-1 and SWIFT-2 trials, 375 and 380 participants, respectively, received depemokimab or placebo in addition to standard care, which included medium- to high-dose inhaled corticosteroids plus at least one additional controller therapy. The trials’ primary endpoint—a statistically significant reduction in asthma exacerbations—was met in both studies. Full data will be presented at an upcoming scientific congress and are expected to support regulatory submissions worldwide.
Research has highlighted the need for simplified treatment regimens in severe asthma. A GSK-conducted survey revealed that 73% of physicians believe that longer dosing intervals could benefit patients managing multiple therapies. Khavandi echoed this sentiment, stating, “This six-month dosing schedule has the potential to address a key unmet need for patients who often face the challenge of juggling complex treatment regimens.”
In addition to SWIFT-1 and SWIFT-2, GSK is conducting the NIMBLE study, which evaluates the efficacy and safety of depemokimab in patients transitioning from other IL-5-targeting therapies, such as mepolizumab or benralizumab. An open-label extension study, AGILE, is also underway to further assess long-term outcomes.
Beyond asthma, depemokimab’s extended half-life and sustained inhibition of IL-5’s inflammatory functions are being explored in other type 2 inflammatory diseases, including eosinophilic granulomatosis with polyangiitis (EGPA), chronic rhinosinusitis with nasal polyps (CRSwNP), and hypereosinophilic syndrome (HES).
“Our ongoing research aims to deliver transformative therapies that address the unmet needs of patients living with severe asthma and other type 2 inflammatory diseases,” Khavandi concluded.
