Depemokimab efficacy/safety in patients with asthma on medium/high-dose ICS: The Phase IIIA randomised SWIFT-1/2 studies

Prérequis/contexte

Depemokimab is the first ultra-long-acting biologic to have enhanced binding affinity for interleukin-5 (IL-5) with high potency inhibition, enabling six-month dosing intervals for patients with asthma.

Objectifs

The primary end point was the annualized rate of exacerbations at 52 weeks. Secondary end points, which were analyzed in a hierarchical manner to adjust for multiplicity, included the change from baseline in the score on the St. George's Respiratory Questionnaire (SGRQ), the forced expiratory volume in 1 second, and asthma symptom reports at 52 weeks.

Méthodes

In these phase 3A, randomized, placebo-controlled replicate trials, we evaluated the efficacy and safety of depemokimab in patients with severe asthma and an eosinophilic phenotype characterized by a high eosinophil count (≥300 cells per microliter in the previous 12 months or ≥150 cells per microliter at screening) and a history of exacerbations despite the receipt of medium- or high-dose inhaled glucocorticoids. Patients were randomly assigned in a 2: 1 ratio to receive either depemokimab (at a dose of 100 mg subcutaneously) or placebo at weeks 0 and 26, plus standard care.

Résultats/discussions

Annualised clinically significant exacerbation rate over 52 weeks in SWIFT-1/2 was significantly lower (58/48%; P < 0.001) for depemokimab vs placebo. Proportions of patients with an adverse event (AE) were similar for depemokimab vs placebo in SWIFT-1 (73%) and lower in SWIFT-2 (72 vs 78%); AEs leading to discontinuation/withdrawal were <3% across groups in both trials. A smaller proportion of depemokimab patients had a serious AE vs placebo (SWIFT-1: 6 vs 17%; SWIFT-2: 7 vs 10%).

Conclusion

Depemokimab significantly reduced exacerbations and was well tolerated in patients with asthma with type 2 inflammation recognised by blood eosinophil count.