Prilenia and Ferrer Announce Pivotal Phase 3 Trial for Pridopidine in ALS Following Encouraging Phase 2 Results
Key Insights
Prilenia Therapeutics (search) and Ferrer (search) unveiled plans for a pivotal Phase 3 study of pridopidine in ALS (search), expected to begin enrollment in January 2026 at leading treatment centers globally.
The trial aims to confirm encouraging Phase 2 data showing improvements in global function, speech, respiratory function, and survival in patients with early and rapidly progressive ALS (search).
New preclinical data demonstrates pridopidine's neuroprotective effects through sigma-1 receptor (search) activation, reducing key ER stress markers by 72% and 52% respectively.
Prilenia Therapeutics (search) B.V. and Ferrer (search) announced their planned pivotal Phase 3 study of pridopidine in amyotrophic lateral sclerosis (search) (ALS (search)) at the Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS) 2025 Annual Meeting in Florida. The trial, expected to begin enrolling participants in January 2026, aims to confirm encouraging post hoc Phase 2 data demonstrating improvements in global function, speech, respiratory function, and survival in patients with early and rapidly progressive ALS.
"The opportunity to potentially bring a much-needed new therapy for a disease as intractable as ALS (search) is exciting and daunting in equal measure," said Dr. Michael R. Hayden, CEO of Prilenia. "Early next year we expect to initiate the study at some of the leading ALS centers in the world, allowing us to begin enrolling participants with early and rapidly progressive ALS."
Phase 3 Trial Design and Endpoints
The randomized, double-blind, placebo-controlled study will feature an initial 48-week double-blind treatment period followed by a 48-week open-label extension phase. The primary endpoint will measure change from baseline in ALSFRS-R scores adjusted for mortality at 48 weeks. Secondary endpoints will include the effect of pridopidine on survival, measures of speech, respiratory (SVC) and bulbar function, and quality of life (ALSAQ-40).
The study will also evaluate patient-reported outcomes of communication and plasma biomarkers. Enrollment will target participants with early and rapidly progressive ALS (search), defined as those with definite or probable ALS by EEC criteria and early in the disease course (less than 18 months since symptom onset). The study population is specifically defined to enable determination of a therapeutic effect within the limited timeframe of the trial.
Enrollment is planned at leading ALS (search) treatment centers in the US, Canada, and European countries, with site opening on a rolling basis subject to local regulatory requirements and regulatory acceptance.
Promising Phase 2 Results Drive Development
The Phase 3 trial builds on encouraging results from the Phase 2 HEALEY ALS (search) platform trial, where pridopidine demonstrated important improvements in global function (ALSFRS-R scores), speech, respiratory function, and survival in people with early and rapidly progressive disease.
"In the phase 2 HEALEY ALS (search) platform trial we have seen important improvements in global function (ALSFRS-R scores), speech, respiratory function and survival with pridopidine in people with early and rapidly progressive disease," said Oscar Pérez, Chief Scientific Officer at Ferrer (search). "Personally, the benefits in terms of speech were of special significance - helping patients to maintain the ability to communicate with their families at such fragile times brings a value that cannot be expressed clinically."
Neuroprotective Mechanism Revealed
New preclinical data presented at NEALS demonstrates pridopidine's neuroprotective effects through activation of the sigma-1 receptor (search) (S1R (search)) by modulating endoplasmic reticulum (ER) stress in iPSC-derived neural progenitor cells. Prolonged ER stress is an early hallmark of ALS (search) and many other neurodegenerative diseases, implicated in increased mitochondrial dysfunction and reduced neuronal survival.
The research showed that pridopidine significantly reduced expression of two key markers of ER stress, BiP and CHOP (search), by 72% and 52% respectively (p<0.0001), correlating with improved cell viability and growth (50% increase, p<0.0001). A selective S1R (search) antagonist was used to block pridopidine's effect and demonstrate that restoration of mitochondrial function and cell survival was indeed S1R-dependent.
Drug Profile and Safety Record
Pridopidine is an investigational, non-invasive, orally administered small molecule sigma-1 receptor (search) (S1R (search)) agonist dosed at 45 mg twice daily. The drug has demonstrated a favorable safety and tolerability profile from placebo-controlled studies and clinical experience involving more than 1,600 people and extending up to seven years.
The drug is currently being utilized in the Accelerating Access to Critical Therapies for ALS (search) (ACT) Expanded Access Program (EAP), supported by a grant from the National Institutes of Health (NIH) - Neurological Disorders and Stroke (NINDS) and run by the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital. This ongoing EAP has completed enrollment of 200 people with ALS who were not eligible for other clinical trials.
Regulatory Status and Future Development
Pridopidine has received Orphan Drug designation in HD and ALS (search) in both the US and EU, and FDA Fast Track designation for the treatment of Huntington's disease (search). In addition to ALS, pridopidine is in late-stage clinical development for HD, with Prilenia and Ferrer (search) planning to initiate a confirmatory study in HD in 2026 designed to confirm pridopidine's effects and support global regulatory approval pathway discussions.
Addressing Critical Unmet Need
ALS (search), also known as Lou Gehrig's disease (search) or motor neuron disease (MND), is a rare, chronic, progressive neurodegenerative disease that affects approximately 500,000 people worldwide. There are approximately 140,000 new cases diagnosed worldwide each year, with an average life span from symptom onset of approximately 2 to 5 years.
In people living with ALS (search), motor neurons in the brain and spinal cord that convey messages to the muscles degenerate, affecting the brain's ability to communicate with muscles. This leads to muscle wasting and progressive paralysis, with patients rapidly losing their ability to walk, speak, eat and breathe, becoming fully dependent on their caretakers. Treatment options remain limited.
Dysfunction of the S1R (search) has been associated with multiple forms of ALS (search), and maintaining S1R functionality may play a key role in protecting neuronal function, providing the scientific rationale for pridopidine's therapeutic approach.