Promising ALS treatment fails to show efficacy in Phase 3 clinical trial

The Phase 3 clinical trial evaluating the terminal complement C5 inhibitor ravulizumab for the treatment of amyotrophic lateral sclerosis (ALS) did not show significant efficacy in slowing the functional decline of participants with ALS.

Despite high hopes, the study concluded that ravulizumab did not demonstrate a meaningful difference compared to a placebo.

The trial enrolled 382 participants who were randomly assigned to receive either ravulizumab or a placebo. The interim analysis, conducted when 33% of participants reached week 26, revealed that ravulizumab did not significantly alter the functional decline compared to the placebo.

At week 50, the observed mean change from baseline in the ALS Functional Rating Scale (ALSFRS-R) score was -14.67 points for those receiving ravulizumab, and -13.33 points for the placebo group. This difference of -1.34 points fell within a confidence interval that did not indicate statistical significance.

The Combined Assessment of Function and Survival (CAFS) analysis at week 50 also showed no substantial difference between the 2 groups, with an average of 5.5 points separating them.

Reference
Genge A, van den Berg LH, Frick G, et al. Efficacy and Safety of Ravulizumab, a Complement C5 Inhibitor, in Adults With Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial. JAMA Neurol. 2023;doi: 10.1001/jamaneurol.2023.2851. Epub ahead of print. PMID: 37695623.