WALTHAM, Mass. — Prilenia Therapeutics B.V. and Ferrer said the US Food and Drug Administration has authorized the start of PREVAiLS, a pivotal Phase 3 clinical study evaluating pridopidine in people with early, rapidly progressive amyotrophic lateral sclerosis. The randomized, placebo-controlled trial will enroll 500 participants, with US site recruitment expected to begin in early 2026. Sites in Europe and other regions will open as their regulatory clearances are obtained.
PREVAiLS, the Pridopidine Phase 3 Study to Evaluate Efficacy and Safety in ALS, will be conducted at up to 60 leading ALS centers across the US, Canada, the EU, the UK and Israel. The trial aims to confirm subgroup findings from the HEALEY ALS Platform Trial, which suggested clinically meaningful improvements in several aspects of ALS progression among participants with rapidly progressive disease early in their diagnosis.
Enrollment will focus on individuals with definite or probable ALS under the El Escorial Criteria who are within 18 months of first symptom onset. The study includes a 48-week double-blind, placebo-controlled period, randomized 3:2 to pridopidine or placebo, followed by a 48-week open-label extension. The primary endpoint is change from baseline in ALSFRS-R adjusted for mortality at week 48. Secondary and exploratory measures will cover respiratory and bulbar function, speech, quality of life, survival effects, patient-reported communication outcomes and plasma biomarkers.
The Phase 3 design is based on analyses from 284 participants in the HEALEY ALS Platform Trial who had rapidly progressive ALS early in their disease course (120 receiving pridopidine; 164 on shared placebo). These findings, accepted for publication in the journal Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, showed a 32 percent slowing of overall progression at 24 weeks, a 62 percent slowing of respiratory decline and an 88 percent reduction in worsening dyspnea. Decline in articulation and speaking rate was also significantly reduced. Investigators additionally reported a 57 percent improvement in survival, with median survival rising from 300 to 600 days among those treated with pridopidine, alongside a favorable safety profile.
“This study has the clear aim of evaluating the efficacy and safety of a much-needed new treatment option for ALS,” said Sabrina Paganoni, MD, PhD, Co-Director of the MGH Neurological Clinical Research Institute and member of the PREVAiLS Steering Committee. “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.”
“These data show the potential for benefits with pridopidine across multiple functional domains, including overall progression, respiratory, bulbar and speech functionality,” said Merit E. Cudkowicz, MD, MSC, Executive Director of the Mass General Brigham Neuroscience Institute and author of the forthcoming ALS & FTD paper. “This, together with the signal of improved survival, provides strong rationale to proceed to Phase 3 evaluation.”
“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 therapy to patients,” said Henk Schuring, Prilenia’s Chief Regulatory and Commercialization Officer. “The publication of the data will give the ALS community a clear view of the foundation for the PREVAiLS design and our confidence in pridopidine’s potential as we work to confirm these results.”
