NEW research has shown that pridopidine, a sigma-1 receptor agonist, does not exhibit a significant impact on the progression of amyotrophic lateral sclerosis (ALS) over a 24-week period.
ALS is a fatal neurodegenerative disease, and the sigma-1 receptor has been identified as a potential therapeutic target. The HEALEY ALS Platform Trial is an innovative, multicenter, phase 2/3 study designed to evaluate multiple treatment regimens efficiently. This specific analysis assessed the effects of pridopidine, a sigma-1 receptor agonist, in patients with ALS. The trial was conducted across 54 sites in the United States from January 2021 to July 2022, enrolling a total of 163 participants who were randomized to receive either pridopidine or placebo.
Participants were assigned in a 3:1 ratio to receive pridopidine (121 individuals) or placebo (42 individuals) over a 24-week period. Additionally, 122 concurrently randomized placebo participants from other treatment regimens within the platform trial were included in the analysis. The primary efficacy outcome was measured using the disease rate ratio (DRR), a statistical model incorporating ALS disease severity, functional decline, and survival outcomes. A DRR below 1 would indicate a slowing of disease progression. The results showed a DRR of 0.99 (95% credible interval, 0.80-1.21), with a probability of DRR <1 at 0.55, indicating no significant difference between pridopidine and placebo. Furthermore, no benefits were observed in secondary endpoints, including bulbar function, respiratory decline, or survival. The most frequently reported adverse events were falls (28.1% in the pridopidine group vs 29.3% in the placebo group) and muscular weakness (24.0% vs 31.7%, respectively).
These findings suggest that pridopidine does not provide clinical benefit in slowing ALS progression. Given the continued unmet need for effective ALS therapies, further research should focus on alternative mechanisms and potential combination treatments. The HEALEY ALS Platform Trial remains an important initiative for accelerating ALS drug development, and ongoing investigations may yield promising future interventions. In clinical practice, these results underscore the necessity of evidence-based treatment approaches, as well as the importance of continued support and symptom management for individuals living with ALS.
Katrina Thornber, EMJ
Reference
Writing Committee for the HEALEY ALS Platform Trial, HEALEY ALS Platform Trial Study Group. Pridopidine in Amyotrophic Lateral Sclerosis: The HEALEY ALS Platform Trial. JAMA. 2025;DOI:10.1001/jama.2024.26429.
