HEALEY ALS Trial: Pridopidine Shows No Impact on Disease Progression in ALS

The findings were published online in JAMA (The Journal of the American Medical Association) on February 17, 2025.

Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disease with limited treatment options. The sigma-1 (σ1) receptor has gained attention as a potential therapeutic target due to its role in cellular protection and neurodegeneration. Jeremy M. Shefner, MD, PhD, Department of Neurology, Barrow Neurological Institute, Phoenix, AZ, and colleagues aimed to evaluate the effects of pridopidine, a selective σ1-receptor agonist, in slowing ALS progression and preserving motor function.

For this purpose, the researchers evaluated pridopidine as part of the HEALEY ALS Platform Trial, a multicenter, phase 2/3 randomized study conducted at 54 sites in the US from January 2021 to July 2022. A total of 163 participants with ALS were assigned to receive either pridopidine or a placebo, with an additional 122 placebo participants included in the analysis. Participants received either 45 mg of oral pridopidine twice daily or a matching placebo for 24 weeks.

The primary outcome measured disease progression using a model integrating functional decline and survival, while secondary outcomes assessed respiratory function, bulbar symptoms, and survival-related measures.

The key findings of the study were as follows:

• The trial included 162 patients with a mean age of 57.5 years, of whom 35% were female.
• A total of 136 participants (84%) completed the study.
• There was no significant difference between pridopidine and placebo in disease progression (DRR: 0.99, 95% credible interval: 0.80-1.21, probability of DRR <1: 0.55).
• There were no improvements in ALS functional rating scale components or survival.
• Pridopidine showed no benefit on secondary outcomes.
• Common adverse events included falls (28.1% in the pridopidine group vs. 29.3% in the placebo group) and muscular weakness (24.0% vs. 31.7%, respectively).

The HEALEY ALS Platform Trial findings indicate that pridopidine did not demonstrate any meaningful impact on disease progression in patients with amyotrophic lateral sclerosis. Over the 24-week study period, there was no significant difference between pridopidine and placebo in terms of disease severity, functional decline, or survival. Additionally, the treatment showed no benefit across key secondary outcomes.

"These results suggest that pridopidine may not be an effective therapeutic option for ALS, highlighting the continued need for further research to identify viable treatments that can slow disease progression and improve patient outcomes," the authors concluded.

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;333(13):1128–1137. doi:10.1001/jama.2024.26429