Twice-Yearly Depemokimab Effectively Lowers Exacerbation Rates in Severe Eosinophilic Asthma: Study Reveals

The findings reveal that administering Depemokimab twice yearly significantly lowers the annualized rate of asthma exacerbations, offering hope for better disease management.

Eosinophilic asthma, characterized by elevated eosinophil levels in the airways, often leads to more severe symptoms and frequent exacerbations compared to other asthma phenotypes. Traditional treatments may not always provide adequate relief, prompting the need for targeted therapies like Depemokimab, which specifically aims to reduce inflammation associated with eosinophils. Depemokimab is a long-acting biologic therapy with improved binding affinity for interleukin-5, potentially allowing for effective dosing every six months.

In this context, David J. Jackson, the King’s College London, London, and colleagues assessed the efficacy and safety of depemokimab in patients with severe asthma characterized by an eosinophilic phenotype. This phenotype was defined by a high eosinophil count (≥300 cells per microliter in the past 12 months or ≥150 cells per microliter at screening) and a history of exacerbations despite receiving medium- or high-dose inhaled glucocorticoids. The evaluation was conducted through phase 3A, randomized, placebo-controlled trials known as SWIFT-1 and SWIFT-2.

Patients were randomly assigned in a 2:1 ratio to receive either 100 mg of depemokimab administered subcutaneously or placebo at weeks 0 and 26, along with standard care. The primary endpoint was the annualized rate of exacerbations at 52 weeks. Secondary endpoints, analyzed hierarchically to account for multiple comparisons, included changes from baseline in the St. George’s Respiratory Questionnaire (SGRQ) scores, forced expiratory volume in one second (FEV1), and reports of asthma symptoms at 52 weeks.

The researchers reported the following findings:

• Across the two trials, 792 patients were randomized, with 762 included in the full analysis—502 received depemokimab and 260 received placebo.
• In the SWIFT-1 trial, the annualized rate of exacerbations was 0.46 for the depemokimab group compared to 1.11 for the placebo group, resulting in a rate ratio of 0.42.
• In SWIFT-2, the annualized rates were 0.56 for depemokimab and 1.08 for placebo, yielding a rate ratio of 0.52.
• No significant differences in the change from baseline in SGRQ scores were found in either trial, precluding statistical inferences for subsequent secondary endpoints.
• In both trials, adverse event occurrence was comparable between the two groups.

The findings showed that depemokimab decreased the annualized rate of exacerbations in patients with severe asthma characterized by an eosinophilic phenotype.

"The study's outcomes signal a promising advancement in asthma care, especially for those suffering from the eosinophilic form of the disease. With ongoing research and potential regulatory approvals on the horizon, Depemokimab could soon become a vital tool in the fight against severe asthma," the researchers concluded.

Reference:

Jackson DJ, Wechsler ME, Jackson DJ, Bernstein D, Korn S, Pfeffer PE, Chen R, Saito J, de Luíz Martinez G, Dymek L, Jacques L, Bird N, Schalkwijk S, Smith D, Howarth P, Pavord ID; SWIFT-1 and SWIFT-2 Investigators. Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype. N Engl J Med. 2024 Sep 9. doi: 10.1056/NEJMoa2406673. Epub ahead of print. PMID: 39248309.