Depemokimab safely reduces exacerbations in severe asthma

Treatment with depemokimab results in a substantial decrease in exacerbations, with an acceptable safety profile, among severe asthma patients with an eosinophilic phenotype, results of the SWIFT-1 and 2 studies have shown.

“Depemokimab significantly reduced exacerbations by 58 percent in SWIFT-1 and [by] 48 percent in SWIFT-2 in patients with type 2 severe asthma characterized by blood eosinophil count,” said lead author Dr David Jackson from Guy’s Severe Asthma Centre, Guy’s and St. Thomas’ NHS Foundation Trust, and the School of Immunology and Microbial Sciences, King’s College London, UK.

“In a heterogenous study population with no symptom eligibility criteria, there was a sustained and significant reduction in exacerbations versus placebo with only two doses of depemokimab administered in a 12-month period,” he added.

In these phase IIIA, randomized, placebo-controlled replicate trials, Jackson and his team examined the safety and efficacy of depemokimab in patients with severe asthma and an eosinophilic phenotype characterized by a high eosinophil count (≥300 cells/μL in the previous 12 months or ≥150 cells/μL at screening) and a history of exacerbations despite receipt of inhaled glucocorticoids.

Eligible patients were randomized 2:1 to receive either depemokimab 100 mg subcutaneously or placebo at weeks 0 and 26 plus standard care. Across SWIFT-1 and 2 trials, 792 patients were randomized (502 to depemokimab and 260 to placebo), and 762 were included in the full analysis.

The annualized rate of exacerbations at 52 weeks served as the primary endpoint, while secondary ones included 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.

SWIFT trials

At 52 weeks, the annualized clinically significant exacerbation rate in both trials was significantly lower (58 percent and 48 percent for SWIFT-1/2, respectively; p<0.001) for depemokimab than placebo. [Jackson, D, et al, ERS 2024]

In SWIFT-1, the annualized exacerbation rate was 0.46 (95 percent confidence interval [CI], 0.36‒0.58) with depemokimab and 1.11 (95 percent CI, 0.86‒1.43) with placebo (rate ratio [RR], 0.42, 95 percent CI, 0.30‒0.59; p<0.001). In SWIFT-2, the rate was 0.56 (95 percent CI, 0.44‒0.70) with depemokimab and 1.08 (95 percent CI, 0.83‒1.41) with placebo (RR, 0.52, 95 percent CI, 0.36‒0.73; p<0.001). [N Engl J Med 2024;doi:10.1056/NEJMoa2406673]

The change from baseline in the SGRQ score did not significantly differ between the treatment groups in either trial. Therefore, no statistical inference was obtained on the other secondary endpoints.

In terms of safety, the proportion of patients who experienced an adverse event (AE) was comparable between depemokimab and placebo in SWIFT-1 (73 percent vs 73 percent) and lower for depemokimab in SWIFT-2 (72 percent vs 78 percent).

In both trials, AEs leading to treatment discontinuation or withdrawal were <3 percent across groups. In addition, serious AEs occurred in fewer patients on depemokimab relative to placebo (SWIFT-1: 6 percent vs 17 percent; SWIFT-2: 7 percent vs 10 percent).

“Depemokimab was well-tolerated in these phase III studies with a rate of AEs similar to placebo, adding to existing phase I safety data,” Jackson said. [Br J Clin Pharmacol 2022;88:701-712]

Depemokimab is an ultra-long-acting biologic therapy with enhanced binding affinity for interleukin-5 that may enable effective 6-month dosing intervals, according to the authors.