FDA Clears Pivotal Phase 3 PREVAiLS Study of Pridopidine in Early, Rapidly Progressive ALS

According to a new announcement, the FDA has cleared the iniatation of a pivotal, 500-patient, randomized, placebo-controlled phase 3 trial dubbed PREVAiLS, which will assess the efficacy and safety of pridopidine (Prilenia Therapeutics/Ferrer) in patients with early-stage, rapidly progressive amyotrophic lateral sclerosis (ALS). The company noted that recruitment at the first clinical trial sites in the United States is planned to begin in early 2026, with international sites expected to follow pending regulatory approval.¹

“This study has the clear aim of evaluating the efficacy and safety of a much-needed new treatment option for ALS,” PREVAiLS steering committee member and investigator Sabrina Paganoni, MD, PhD, co-director of Massachusetts General Hospital Neurological Clinical Research Institute, said in a statement.¹ “Early detection and management are essential for preserving function, with slowing of functional decline, maintaining speech and prolonging survival being ALS therapeutic priorities. This makes pridopidine’s S1R activation mechanism of particular interest, holding promise in ALS by enhancing key cellular mechanisms and promoting neuroprotection."

PREVAiLS will enroll adults diagnosed with definite or probable ALS who are within 18 months of symptom onset across up to 60 ALS treatment centers worldwide. The trial design consists of a 48-week double-blind, placebo-controlled phase, randomized 3:2 to receive either pridopidine or placebo, followed by a 48-week open-label extension. The primary end point is change from baseline in the ALS Functional Rating Scale–Revised (ALSFRS-R), adjusted for mortality, at 48 weeks while secondary and exploratory end points include measures of speech, respiratory and bulbar function, quality of life, survival, patient-reported outcomes, and plasma biomarkers.

The phase 3 trial is based on subgroup analyses of 284 participants with early-stage rapidly progressive ALS from the phase 2/3 HEALEY ALS platform trial (NCT04297683), including 120 participants in the pridopidine group and 164 in the shared placebo group.² Overall, results from these analyses suggested potential benefits of pridopidine across multiple domains, including disease progression, speech, and survival.

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The subgroup analyses, described in a manuscript accepted for publication in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration (ALS & FTD), showed a 32% slowing of overall progression as measured by the ALSFRS-R (P = .03), a 62% reduction in worsening of respiratory function (P = .03), and an 88% slowing of decline in dyspnea (P = .005) at 24 weeks. Notably, findings showed that articulation and speaking rate deterioration were reduced by 93% (P = .0007) and 70% (P = .002), respectively (p-values nominal). The analyses also indicated a 57% improvement in survival for participants receiving pridopidine, with median survival prolonged from 300 to 600 days (n = 49; 37 in the pridopidine-to-pridopidine early-start group and 12 in the placebo-to-pridopidine delayed-start group), along with a favorable safety profile.

“These data show the potential for benefits with pridopidine - seen across multiple functional domains including overall progression, respiratory, bulbar and speech functionality. This together with the signal of improved survival provides strong rationale to proceed to Phase 3 evaluation of pridopidine,” PREVAiLS steering committee member Merit E. Cudkowicz, MD, MSC, executive director Mass General Brigham Neuroscience Institute, director of the Sean M. Healey & AMG Center for ALS at Mass General Brigham, said in a statement.¹

“The FDA’s clearance to start PREVAiLS is significant, providing an immediate opportunity to begin a pivotal Phase 3 study with the aim of bringing a promising, oral, well tolerated new therapy to patients,” Henk Schuring, chief regulatory and commercialization officer at Prilenia, said in a statement.¹ “The publication of the data by ALS & FTD will provide the ALS community with a clear view of the basis for the design of PREVAiLS and our confidence in pridopidine’s capabilities, as we aim to confirm pridopidine’s results in this population of people living with ALS.”

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REFERENCES
1. 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
2. Writing Committee for the HEALEY ALS Platform Trial, Shefner JM, Oskarsson B, et al. Pridopidine in Amyotrophic Lateral Sclerosis: The HEALEY ALS Platform Trial. JAMA. Published online February 17, 2025. doi:10.1001/jama.2024.26429