FDA clears pivotal Phase 3 trial of new ALS oral therapy pridopidine
Study focuses on people early in ALS whose symptoms are progressing quickly
- FDA cleared the start of a pivotal Phase 3 trial testing pridopidine, an oral therapy for ALS.
- The study will enroll people with early, rapidly progressive ALS.
- Earlier subgroup analyses suggested pridopidine may slow disease progression and improve survival in some patients.
The U.S. Food and Drug Administration (FDA) has cleared the start of a pivotal Phase 3 clinical trial testing the oral therapy pridopidine in people with amyotrophic lateral sclerosis (ALS).
Dubbed PREVAiLS, the trial will assess pridopidine’s efficacy and safety in up to 500 people with early, rapidly progressive ALS, according to developers Prilenia Therapeutics and Ferrer.
Pending local clinical trial clearance, the study will be conducted in up to 60 leading ALS treatment centers across the U.S., Canada, the European Union, the U.K., and Israel.
Recruitment is expected to begin at the first U.S. sites in early 2026. If results are positive, the trial could form the basis for a regulatory application seeking the approval of pridopidine for ALS.
“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, Prilenia’s chief regulatory and commercialization officer, said in a company press release.
Trial design focuses on early, rapidly progressing ALS
The design of PREVAiLS builds on potentially clinically meaningful improvements observed with pridopidine in subgroup analyses from the HEALEY ALS trial (NCT04297683), a multi-arm study that tested multiple ALS treatments simultaneously against a shared placebo group.
This arm of HEALEY failed to meet its main goal of showing that pridopidine could slow disease progression, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R), in the overall population at 24 weeks (about six months).
But among people with rapidly progressive ALS who were within 18 months of symptom onset, pridopidine was associated with a significant 32% slowing of disease progression at 24 weeks, based on subgroup analyses. Treatment was also linked to a 62% slowing in respiratory function decline and an 88% reduction in worsening of shortness of breath over the same period.
Speech measures also showed benefit, with articulation deteriorating at a 93% slower rate and speaking rate declining 70% more slowly at 24 weeks, based on subgroup analyses.
A separate analysis including 49 participants suggested a 57% improvement in survival, with median survival extended from 300 days (about 10 months) to 600 days (about 20 months). Overall, the therapy showed a favorable safety and tolerability profile, according to the researchers.
These findings have been accepted for publication in the journal Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration (ALS & FTD).
“These data show the potential for benefits with pridopidine – seen across multiple functional domains including overall progression, respiratory, bulbar and speech functionality,” said Merit E. Cudkowicz, MD, director of the Sean M. Healey & AMG Center for ALS at Mass General Brigham and PREVAiLS Steering Committee member and author on the ALS & FTD paper. “This together with the signal of improved survival provides strong rationale to proceed to Phase 3 evaluation of pridopidine.”
Study aims to confirm earlier subgroup findings
Aiming to confirm HEALEY’s findings in this subgroup of ALS patients, PREVAiLS will enroll people with definite or probable ALS, whose symptoms began within the past 18 months, and whose disease is progressing rapidly.
Participants will be randomly assigned to receive either pridopidine or a placebo for 48 weeks (about 11 months), with three out of every five participants receiving the active treatment. This will be followed by a 48-week open-label extension, during which all participants will receive pridopidine.
“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,” Schuring said.
The trial’s main goal is to assess changes in ALSFRS-R adjusted for mortality. Secondary and exploratory measures will examine effects on speech, breathing, and bulbar function, as well as quality of life, survival, patient-reported communication outcomes, and blood-based biomarkers.
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.
“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 Neurological Clinical Research Institute at Mass General Hospital 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,” Paganoni added.
The developers, who entered into an agreement earlier this year to co-develop and commercialize pridopidine in Europe and other select markets, said a study website with additional trial details will be launched soon.
Pridopidine is also being used in an expanded access program (NCT06069934) run by the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital, which has completed enrollment of 200 people with ALS.
The program is designed to provide access to the therapy for people who were not eligible to participate in clinical trials, while offering developers an additional avenue to gather safety and efficacy data that may support regulatory applications.
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