Prilenia Therapeutics B.V. and Ferrer  announced that the US Food and Drug Administration (FDA) has cleared the start of the pivotal, 500-patient, randomized, placebo-controlled Phase 3 study of pridopidine in participants with rapidly progressive amyotrophic lateral sclerosis (ALS) early in their disease course. Recruitment is planned to begin at the first US clinical trial sites in early 2026, with sites in Europe and other regions to follow, pending local clinical trial clearance.

PREVAiLS (Pridopidine Phase 3 Study to Evaluate Efficacy and Safety in ALS) will be conducted in up to 60 leading ALS treatment centers across the US, Canada, EU, UK and Israelⁱⁱ. Aiming to confirm pridopidine’s Phase 2 data, the study will target the same subgroup population, enrolling participants with definite or probable ALS (El Escorial Criteria) and who are within 18 months from first onset of disease symptoms.

The study will consist of an initial 48-week double-blind placebo-controlled phase, randomized on a 3:2 (pridopidine:placebo) basis, followed by a 48-week open-label extension phase. The primary endpoint will be the change from baseline in ALSFRS-R adjusted for mortality at 48 weeks. Secondary and exploratory endpoints will include measures of speech, respiratory function, bulbar function, quality of life and effect of pridopidine on survival, as well as patient-reported outcomes of communication and plasma biomarkersⁱⁱⁱ. 

PREVAiLS is predicated on subgroup analyses of data from 284 subjects with rapidly progressive ALS early in their disease course (120 in the pridopidine group and 164 in the shared placebo group) from the Phase 2 HEALEY ALS Platform trial, showing potentially clinically meaningful improvements with pridopidine in multiple domains of disease progression, speech and survival.

These subgroup analyses from the HEALY ALS Platform Trial, described in a manuscript accepted for publication in the peer-reviewed journal Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration (ALS & FTD), showed a 32% slowing of overall progression (ALSFRS-R, p=0.03), a 62% slowing of respiratory function worsening (p=0.03) and slowing of decline of dyspnea by 88% (p=0.005), with articulation and speaking rate deterioration reduced by 93% (p=0.0007) and 70% (p=0.002) respectively, at 24 weeks (p-values nominal).

These data also showed a 57% improvement in survival benefit for patients taking pridopidine, prolonging median survival time from 300 to 600 days (n=49, 37 pridopidine-to-pridopidine, early start group, 12 placebo-to-pridopidine, delayed start group)^iv, and a favorable safety profileⁱ.

“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, MGH Neurological Clinical Research Institute (NCRI) and PREVAiLS Steering Committee member and investigator. “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”.

“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,” said 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, PREVAiLS Steering Committee member and author on the ALS & FTD paper.

“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,” said Henk Schuring, Prilenia’s Chief Regulatory and Commercialization Officer. “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.”