PREVAiLS Phase 3 Trial Evaluates Pridopidine in Early, Rapidly Progressive ALS

Enrollment is underway in the ongoing phase 3 PREVAiLS trial (NCT07322003), a randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of pridopidine (Prilenia Therapeutics/Ferrer), an oral, selective sigma-1 receptor agonist, in patients with early, rapidly progressing amyotrophic lateral sclerosis (ALS). The trial, highlighted in an abstract presented at the 2026 Network of Excellence for ALS (NEALS) Annual Meeting, held October 27-30 in Clearwater, Florida, aims to determine whether pridopidine can slow disease progression in this patient population.¹

Led by Leonard H. van den Burg, MD, PhD, professor of neurology at University Medical Center Utrecht in the Netherlands, PREVAiLS is designed to prospectively evaluate these findings in a larger population of patients with early, rapidly progressing ALS. The study plans to enroll 500 participants who will be randomized in a 3:2 ratio to receive pridopidine 45 mg twice daily or placebo, both in addition to standard of care. The double-blind treatment period will last 48 weeks, followed by a 48-week open-label extension.

The primary endpoint is change from baseline in ALSFRS-R scores adjusted for mortality at week 48. Secondary endpoints include survival, quantitative assessments of speech, respiratory and bulbar function, and quality of life, as measured by the Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40). Exploratory measures will include biomarkers such as neurofilament light (NfL), as well as patient-reported outcomes related to communication.

The trial's design is informed by subgroup findings from the Phase 2 HEALEY ALS Platform Trial (NCT04615923), which evaluated pridopidine in regimen D. Although the study did not meet its primary endpoint, a post hoc analysis of participants with definite or probable ALS within 18 months of symptom onset suggested potential treatment effects across several functional domains. At 24 weeks, pridopidine was associated with slower declines in total ALS Functional Rating Scale–Revised (ALSFRS-R) scores (P = .03) and respiratory function (P = .03), with a trend toward benefit in bulbar function (P = .06) compared with placebo.¹

Additional findings from the phase 2 analysis favored pridopidine in measures of speaking and articulation rate (P = .002 and P = .0007, respectively). Median survival was 600 days in the early-start pridopidine group compared with 300 days in the delayed-start group, although this difference did not reach statistical significance (log-rank P = .069). Safety and tolerability were comparable with placebo.¹

Previously,the FDA’s clearance of PREVAiLS in December 2025allowed the pivotal study to move forward.² At the time, the trial was planned to enroll 500 participants across approximately 60 ALS treatment centers worldwide, with the goal of confirming earlier subgroup findings involving functional progression, speech, respiratory outcomes, and survival.

REFERENCES
1. Van den Burg LH, Genge A, van Eijk R, et al. PREVAiLS (Pridopidine Phase 3 Study To Evaluate Efficacy And Safety In ALS) a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study In ALS. Presented at: The Network of Excellence for ALS Annual Meeting. October 27-30, 2026; Clearwater, Florida.
2. Prilenia and Ferrer Announce FDA Clearance to Start the “PREVAiLS” Pivotal Phase 3 Study with Pridopidine in ALS. News release. Prilenia Therapeutics. December 11, 2025. Accessed December 11, 2025. https://news.prilenia.com/press-releases/press-release-details/2025/Prilenia-and-Ferrer-Announce-FDA-Clearance-to-Start-the-PREVAiLS-Pivotal-Phase-3-Study-with-Pridopidine-in-ALS/default.aspx