Prilenia and Ferrer Launch Pivotal Phase 3 Trial of Pridopidine for Rapidly Progressive ALS
核心洞察
Prilenia Therapeutics (搜索) and Ferrer (搜索) have enrolled the first participant in PREVAiLS, a global 500-participant Phase 3 study evaluating pridopidine's efficacy in slowing ALS (搜索) progression in early, rapidly progressive patients.
The study design is based on promising subgroup analysis data from a Phase 2 HEALEY ALS (搜索) Platform Trial, where pridopidine showed effects in rapid progressive patients despite the full trial not meeting primary endpoints.
PREVAiLS is believed to be the only currently recruiting Phase 3 ALS (搜索) study and will take place across up to 60 leading treatment centers in 13 countries.
Prilenia Therapeutics (搜索) B.V. and Ferrer (搜索) announced the enrollment of the first participant in their pivotal Phase 3 study of pridopidine for rapidly progressive Amyotrophic Lateral Sclerosis (搜索) (ALS (搜索)). The PREVAiLS trial (NCT07322003) represents a critical milestone in ALS drug development, as it is believed to be the only currently recruiting Phase 3 ALS study.
The first participant was enrolled at Mass General Brigham (搜索) under the supervision of Sabrina Paganoni, MD, PhD, Co-Director of the MGH Neurological Clinical Research Institute and PREVAiLS principal investigator. "Pridopidine is a sigma-1 receptor (搜索) (S1R (搜索)) agonist. The S1R has been shown to play a role in stimulating multiple neuroprotective pathways impaired in neurodegenerative diseases, such as ALS (搜索) and Huntington's disease (搜索)," said Paganoni. "Enrolling the first participant in this confirmatory study is a milestone in our search for potential new therapeutic options that may help to slow disease progression, preserve function, maintain speech and prolong survival – key aims of early ALS therapy."
Study Design and Rationale
PREVAiLS is a 48-week randomized, placebo-controlled study with a 3:2 pridopidine to placebo ratio, targeting 500 participants with rapidly progressive ALS (搜索) early in their disease course. The study includes a 48-week open-label extension phase and seeks to enroll participants with definite or probable ALS who are within 18 months from first onset of disease symptoms.
The trial design is informed by peer-reviewed and published data from a subgroup analysis of the randomized, double-blind, placebo-controlled Phase 2 HEALEY ALS (搜索) Platform Trial. While the HEALEY trial did not meet its primary or secondary endpoints in the full population, pre-specified and additional analyses showed effects in rapid progressive patients (pridopidine: n = 37; shared placebo: n = 35) that PREVAiLS seeks to confirm.
The primary endpoint is the change from baseline in ALSFRS-R adjusted for mortality at 48 weeks. Secondary and exploratory endpoints include survival and measures of speech, respiratory function, bulbar function and quality of life, as well as patient-reported outcomes of communication and plasma biomarkers.
Global Study Implementation
The study is set to take place in up to 60 leading ALS (搜索) treatment centers across 13 countries. Eleven sites are already initiated or will be imminently, with recruitment at additional sites in the US, Canada, EU, UK and Israel expected to commence in the coming weeks and months.
"The ALS (搜索) community urgently needs new treatment options that can delay the disease's relentless progression, and awaits the outcome of this study," said Kuldip Dave, Ph.D., Senior Vice President of Research at the ALS Association (搜索). "The earlier we can diagnose and treat ALS, the greater the potential to preserve function and maintain quality of life for longer, which are key to making ALS livable until we can cure it."
Pridopidine's Mechanism and Safety Profile
Pridopidine is an investigational selective, orally administered sigma-1 receptor (搜索) agonist dosed at 45 mg twice daily. The sigma-1 receptor has been shown to play a role in stimulating multiple neuroprotective pathways impaired in neurodegenerative diseases. Dysfunction of the S1R (搜索) has been associated with multiple forms of ALS (搜索), and maintaining S1R functionality may play a key role in protecting neuronal function.
In clinical studies to date, pridopidine has demonstrated a favorable safety and tolerability profile, with data from more than 1,600 people, mostly from Huntington's disease (搜索) studies, some of whom have received active treatment for up to seven years. The drug has Orphan Drug designation in HD and ALS (搜索) in the US and EU, and FDA Fast Track designation for the treatment of HD.
Disease Context and Unmet Need
ALS (搜索) affects approximately 500,000 people worldwide and is more frequent in men than in women. The average survival is 2 to 5 years, and the disease typically appears in individuals aged 40 to 70. ALS presents a range of symptoms, including muscle weakness and atrophy, mobility issues, muscle spasms, difficulty speaking clearly, trouble swallowing, fatigue, and emotional and cognitive changes. Current treatment options are limited.
In addition to ALS (搜索), Prilenia and Ferrer (搜索) are planning to initiate a potentially registrational pivotal Phase 3 study in Huntington's disease (搜索), with recruitment expected to start in the first half of 2026.