Twice-Yearly Depemokimab vs. Short-Acting Biologics in Asthma
Publication Title: Switching to twice-yearly depemokimab from mepolizumab/benralizumab in severe asthma: a multicenter, randomized, double-blind, phase 3A clinical trial (NIMBLE)
Summary
- Question
- This study examined whether individuals with severe asthma, who were successfully managed with short-acting biologics targeting interleukin-5 (IL-5) or its receptor, could switch to depemokimab, an ultra-long-acting biologic requiring only twice-yearly injections, while maintaining asthma control. The main objective was to determine if depemokimab was as effective (noninferior) as continuing current treatments (mepolizumab or benralizumab) in preventing asthma exacerbations over one year.
- Why it Matters
- Severe asthma can significantly disrupt daily life and often requires frequent medication. Biologic therapies, such as mepolizumab and benralizumab, target IL-5, a protein involved in inflammation, and help reduce asthma exacerbations. However, these treatments require injections every four to eight weeks, which can be inconvenient and reduce adherence. Depemokimab offers a longer dosing interval of six months, potentially improving convenience and treatment adherence. This study is significant as it evaluates whether patients can safely transition to depemokimab without losing the benefits of their current biologic therapy.
- Methods
- The researchers conducted a multicenter, randomized, double-blind, phase 3A trial involving 1,717 participants aged 12 years or older with severe asthma. All participants had been on mepolizumab or benralizumab for at least a year and showed clinical improvement. They were randomly assigned to either switch to depemokimab (100 mg every six months) or continue their existing treatment. The primary outcome measured was the annual rate of asthma exacerbations over 52 weeks. Secondary outcomes included asthma control, quality of life, lung function, and safety.
- Key Findings
- While switching to depemokimab resulted in slightly higher annual exacerbation rates (0.57 vs. 0.49 exacerbations per year), most participants in both groups experienced no exacerbations. Health-related quality of life, asthma control, and lung function remained stable across both groups. Adverse events were similar between treatments, with no new safety concerns identified. Noninferiority (similar effectiveness) was not statistically proven due to a small margin exceeding the pre-defined threshold.
- Implications
- The findings suggest that most individuals with severe asthma currently benefiting from mepolizumab or benralizumab can switch to depemokimab and maintain asthma control. Depemokimab’s twice-yearly dosing schedule may improve convenience and adherence, reducing the burden of frequent injections. However, a small subset of patients, particularly those switching from benralizumab, might experience a slight increase in exacerbations.
- Next Steps
- Future research should investigate the specific characteristics of patients who may be less suited for a switch to depemokimab. Additional studies could also explore the long-term effects of switching biologics and assess patient preferences and adherence with less frequent dosing schedules.
- Funding Information
- This research was supported by GSK (GSK ID: 206785). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Yale University also provided funding and support for this research.
Full Citation
Chupp G, Nagase H, Skowasch D, Devouassoux G, Côté A, Jackson D, Jackson D, Wechsler M, Imber V, McGinniss J, Sherine O, Howarth P, Pavord I, Chupp G, Nagase H, Skowasch D, Devouassoux G, Côté A, Jackson D, Jackson D, Wechsler M, Imber V, McGinniss J, Sherine O, Howarth P, Pavord I. Switching to twice-yearly depemokimab from mepolizumab/benralizumab in severe asthma: a multicenter, randomized, double-blind, phase 3A clinical trial (NIMBLE). American Journal Of Respiratory And Critical Care Medicine 2026, 212: 921-935. PMID: 41738176, PMCID: PMC13160935, DOI: 10.1093/ajrccm/aamag031.
This AI-assisted summary has been reviewed and approved by at least one of the study's authors to ensure it accurately reflects the research.
Authors
Geoffrey Chupp, MD
First AuthorProfessor of Medicine (Pulmonary, Critical Care and Sleep Medicine )
Ian D Pavord
Last Author
Other Authors
Research Themes
Concepts
- clinically significant exacerbations;
- severe asthma;
- significant exacerbations;
- double-blind;
- adverse events;
- annual rate of clinically significant exacerbations;
- rate of clinically significant exacerbations;
- non-inferiority;
- interleukin-5;
- health-related quality;
- safety of switching;
- ultra-long-acting;
- statistical non-inferiority;
- non-inferiority study;
- non-inferiority margin;
- lung function outcomes;
- double-dummy;
- primary endpoint;
- biologic therapy;
- health-related quality of life;
- exacerbation rate;
- safety endpoints;
- clinical benefit;
- treatment arms;
- parallel-group