Medical Journal Reviews

Depemokimab (GSK3511294) is a novel humanized IgG1 anti-IL-5 monoclonal antibody. Eosinophils, driven by interleukin-5 (IL-5), play a central role in more than 70% of severe asthma patients. While existing biologics targeting IL-5 have improved outcomes, their dosing schedules can be burdensome for lifelong treatment. Depemokimab (GSK3511294) is a novel humanized IgG1 anti-IL-5 monoclonal antibody. Compared to its predecessor mepolizumab, depemokimab fragment crystallizable (Fc) region has an amino acid modification (YTE modification) that extends its half-life, allowing for biannual dosing. In two Phase 3 randomized, placebo-controlled trials—SWIFT-1 and SWIFT-2—732 patients with severe eosinophilic asthma received 100 mg of depemokimab subcutaneously every six months over a 52-week period. The trials showed that depemokimab significantly reduced the annualized exacerbation rate by 54% compared to placebo (Rate Ratio 0.46; P < 0.0001). Blood eosinophil counts dropped rapidly by approximately 80% and remained suppressed throughout the study. The safety profile was favorable, aligning with previous anti-IL-5 treatments.

However, despite the reduction in exacerbations and eosinophil counts, there were no significant improvements in asthma symptoms or lung function between the depemokimab and placebo groups. This suggests that there may be not-so-subtle differences in efficacy when long duration between dosing occurs. Future research should explore depemokimab impact on airway eosinophils and IL-5. The forthcoming NIMBLE trial will provide insights into depemokimab efficacy in well-controlled patients transitioning from other anti-IL-5/Rα therapies administered at shorter intervals.

Professor David Jackson (Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London), first author of the article published in The New England Journal of Medicine, commented on the importance of this study, as follows: "Whilst we already have several excellent, highly effective anti-IL-5/5Rα biologic therapies for our patients with severe asthma, as clinicians we face additional challenges that are often under-reported. These include issues with adherence to biologic therapies when patients transfer to home administration, those with needle phobia who still request to attend clinic for every dose, and patients who feel that the current dosing intervals are suboptimal describing symptoms increasing in the one to two weeks prior to their next scheduled dose. All of these patients may particularly benefit from an anti-IL-5 therapy like depemokimab that only needs to be dosed every 6 months".