Pridopidine Phase 3 trial to start enrolling early next year
Study seeks patients with early, rapidly progressive ALS
A pivotal Phase 3 clinical trial testing the oral therapy pridopidine in people with amyotrophic lateral sclerosis (ALS) is expected to start in January, following promising results seen in the HEALEY ALS platform trial.
Pending regulatory clearance, enrollment will begin at ALS treatment centers in the U.S., Canada, and Europe, said developers Prilenia Therapeutics and Ferrer. If results are positive, the trial could form the basis for applications seeking the approval of pridopidine for ALS.
“The opportunity to potentially bring a much-needed new therapy for a disease as intractable as ALS is exciting and daunting in equal measure,” Michael R. Hayden, PhD, CEO of Prilenia, said in a company press release. “The ALS community deserves to see progress in the management of the disease – we hope to make some of that progress.”
Details about the trial are scheduled to be presented at the 2025 Annual Meeting of the Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS), being held Oct. 7-10 in Clearwater, Florida, and online.
The companies said they expect the study to enroll people with early and rapidly progressive ALS, who will be randomly assigned to receive pridopidine or a placebo for 48 weeks (about a year). Then all participants will be given pridopidine for another 48 weeks. The main goal will be to see if pridopidine can slow disease progression, as measured with a standard scale called the ALS Functional Rating Scale Revised (ALSFRS-R). The study will also assess the treatment’s effects on survival, speech, breathing function, and quality of life.
Promising trends
ALS is marked by the progressive death of motor neurons, the nerve cells that control movement. Pridopidine is an oral small molecule designed to activate a nerve protein called the sigma-1 receptor (S1R), which can reduce cellular stress and improve the survival of nerve cells.
Pridopidine was tested as part of HEALEY ALS trial (NCT04297683), a multi-arm trial that is simultaneously evaluating several ALS treatments. In the pridopidine arm, researchers had hoped to show that the experimental therapy could slow disease progression relative to a placebo, but results showed no significant difference in ALSFRS-R scores after about six months.
Still, some promising trends were noted. For example, data indicated that patients given pridopidine retained better speaking abilities than those given a placebo, which researchers said could be meaningful for patients in day-to-day life.
There also were trends towards slower disease progression in the subset of patients with rapidly progressing disease who started treatment soon after their diagnosis — essentially the same population that will now be enrolled in the pivotal Phase 3 study.
The trial showed “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. “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.”
“These signals provide hope that a sigma-1 receptor agonist like pridopidine can have a major positive impact for people living with ALS, and being on the cusp of being able to further explore that potential is a privilege,” Pérez said.
Prilenia and Ferrer entered into an agreement to codevelop and commercialize pridopidine in Europe and certain other markets earlier this year.
About the Author
