ALS Therapy Trial Fails to Benefit Patients Over Placebo

Because treatment options for amyotrophic lateral sclerosis (ALS) are lacking, a phase 2 trial of reldesemtiv aimed to determine whether the drug slows disease progression. The COURAGE-ALS trial was a double-blind, placebo-controlled phase 3 randomized trial conducted across 83 ALS centers in 16 countries between August 2021 and July 2023. Results were published in JAMA Neurology.

The first 24-week period included reldesemtiv 300 mg or placebo; all participants received reldesemtiv 300 mg during the second 24-week period, with a 4-week follow-up. Criteria for participant inclusion was definite, probable, or possible ALS with lower motor neuron signs by modified El Escorial Criteria; ALS symptoms for 24 months or less; ALS Functional Rating Scale-Revised (ALSFRS-R) total score of 44 or less; and forced vital capacity greater than or equal to 65% of predicted.

The study included 486 participants (mean age, 59.4 years); 325 were randomly assigned to reldesemtiv, and 161 were randomly assigned to placebo. The second 24-week interim analysis included 256 patients. The mean difference in the ALSFRS-R score from baseline to week 24 was -1.1 (0.53; 95% CI, -2.17 to -0.08; P=0.04), favoring placebo. The win probability was 0.44 for reldesemtiv and 0.49 for placebo, with a win ratio of 0.91 (95% CI, 0.77-1.10; P=0.11).

Given the significant amount of missing data due to early termination, a combined assessment was prioritized, but this also failed to demonstrate a benefit from reldesemtiv. “In the COURAGE-ALS randomized clinical trial, the overall development of FSTAs evaluated an important clinical hypothesis with great rigor. The results, although not supportive of future development for ALS, are clear and important,” the researchers concluded.

Reference

Shefner JM, Cudkowicz ME, Genge A, et al. Reldesemtiv in amyotrophic lateral sclerosis: results from the COURAGE-ALS randomized clinical trial. JAMA Neurol. Published online March 24, 2025. doi:10.1001/jamaneurol.2025.0241