Abstract Rationale Depemokimab is the first ultra-long-acting biologic with enhanced interleukin-5 binding affinity, high potency, and an extended half-life, enabling twice-yearly dosing in patients with asthma. In the Phase III SWIFT-1/-2 studies, depemokimab significantly reduced exacerbations by 54% with sustained suppression of inflammation assessed by blood eosinophil count (BEC) observed in patients with type 2 asthma. However, the efficacy and safety of depemokimab in adolescent patients with asthma has not been specifically characterized to date. Methods In the SWIFT-1/-2 trials, patients with type 2 asthma characterized by BEC and ≥2 exacerbations (past year) were randomized 2:1 to receive depemokimab 100 mg or placebo subcutaneously every 26 weeks, in addition to standard care. The primary endpoint was the annualized rate of clinically significant exacerbations (CSEs) over 52 weeks. Here, we report a prespecified analysis of the primary endpoint and safety data among adolescent patients (aged 12-17 years) in the pooled SWIFT-1/-2 populations. Given the low patient numbers, a prespecified Bayesian dynamic borrowing approach was used to support the extrapolation of the primary endpoint from adults to adolescents. Results The pooled SWIFT-1/-2 population comprised 30 adolescents (15 treated with depemokimab) and 732 adults. The annualized rates of CSEs were consistent across adolescents and adults, with 43% and 54% rate reductions (rate ratio 95% confidence interval: 0.57 0.15, 2.13 and 0.46 0.36, 0.58), respectively, for depemokimab versus placebo. The Bayesian dynamic borrowing approach indicated that the minimum prior weight leading to the equivalent of a statistically significant p-value was 0.6. The point estimate was consistent across borrowing scenarios (Figure). A similar proportion of participants with any adverse event (AE) was observed in the adolescent versus adult treatment groups (73% vs 72%). Among adolescent participants, 2 AEs were reported as treatment-related and 1 serious AE was reported (abdominal pain, which was not considered treatment-related by the investigator, and was reported as resolved with sequelae). No deaths or AEs leading to study withdrawal were reported among adolescents. Conclusions Twice-yearly depemokimab reduced exacerbations and was well tolerated in adolescents in the SWIFT-1/-2 trials, though patient numbers were low. Given prior clinical knowledge of similarities between adult and adolescent patients with asthma, borrowing 60% of adult data is assumed to be reasonable to support extrapolating the impact of depemokimab on CSEs from adults to adolescents. Findings from this analysis support a favorable benefit-risk profile of depemokimab for adolescents. This abstract is funded by: GSK (214099; 206713/213744; NCT04719832/NCT04718103)
Jackson et al. (Fri,) studied this question.