THE COURAGE-ALS clinical trial, evaluating the efficacy of reldesemtiv in slowing disease progression in amyotrophic lateral sclerosis (ALS), found no significant benefit, leading to its early termination for futility.
This international phase 3 trial, conducted across 83 centres in 16 countries, included 486 participants who met stringent eligibility criteria for ALS diagnosis and severity. Participants were randomised to receive either oral reldesemtiv (300 mg twice daily) or placebo for 24 weeks, with a subsequent open-label period. The primary endpoint was the change in the ALS Functional Rating Scale-Revised (ALSFRS-R) score from baseline to week 24. At the second planned interim analysis, the mean group difference in ALSFRS-R scores was −1.1 (95% CI, −2.17 to −0.08; P = .04), favouring placebo. Secondary endpoints, including combined assessments of function and survival, also failed to demonstrate efficacy (win ratio: 0.91; 95% CI, 0.77–1.10; P = .11). The trial was discontinued due to these findings, with adverse event rates comparable between groups.
These results underscore the challenges of developing effective therapies for ALS and highlight the need for innovative approaches in clinical research. Despite promising phase 2 data suggesting potential benefits of reldesemtiv, its lack of efficacy in this larger trial emphasises the complexity of ALS pathophysiology and treatment response variability. Future research should focus on refining patient selection criteria, exploring combination therapies, and leveraging biomarkers to better predict treatment outcomes. For clinicians, these findings reinforce the importance of managing patient expectations regarding experimental therapies while continuing to prioritise symptom management and supportive care.
Reference
Shefner JM et al. Reldesemtiv in amyotrophic lateral sclerosis: results from the COURAGE-ALS randomized clinical trial. JAMA Neurol. 2025;DOI:10.1001/jamaneurol.2025.0241.
