Trial of experimental ALS therapy pridopidine enrolls first participant
PREVAiLS will test treatment in people with early, rapidly progressive ALS
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- PREVAiLS is a Phase 3 trial testing pridopidine in people with early, rapidly progressive ALS.
- The study will evaluate whether pridopidine can slow disease progression and help preserve speech and survival..
- Pridopidine is designed to activate the sigma-1 receptor (S1R), which is involved in neuroprotective pathways.
A pivotal Phase 3 clinical trial testing pridopidine, an experimental oral therapy being developed by Prilenia Therapeutics and Ferrer, in people with early, rapidly progressive amyotrophic lateral sclerosis (ALS) has enrolled its first participant.
PREVAiLS (NCT07322003), which was cleared late last year by the U.S. Food and Drug Administration, will involve about 500 patients with definite or probable ALS who first experienced symptoms within the past 18 months. The trial is believed to be the only Phase 3 study currently enrolling people with ALS.
Global trial will enroll patients across multiple countries
Recruitment will take place at up to 60 leading ALS treatment centers across 13 countries, including the U.S., Canada, the European Union, the United Kingdom, and Israel. Eleven sites are already open or about to open, and more sites are expected to begin enrolling patients in the coming weeks or months.
“The ALS community urgently needs new treatment options that can delay the disease’s relentless progression, and awaits the outcome of this study,” Kuldip Dave, PhD, senior vice-president of research at the ALS Association, said in a press release. “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.”
The first participant was enrolled at Mass General Brigham in Boston, under the supervision of PREVAiLS principal investigator Sabrina Paganoni.
The trial aims to confirm previous Phase 2 findings and evaluate the effects of pridopidine on disease progression, speech, and survival in people with early, rapidly progressive ALS. If results are positive, the trial could form the basis for regulatory applications seeking pridopidine’s approval.
For Paganoni, MD, PhD, co-director of the Mass General’s Neurological Clinical Research Institute, “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.”
Experimental therapy aims to protect nerve cells in ALS
ALS damages motor neurons, the nerve cells that control voluntary movements, causing them to die. As these cells are lost, the brain can no longer control muscles, and patients experience progressive weakness and gradually lose the ability to perform daily tasks.
Pridopidine is designed to activate the sigma-1 receptor (S1R), a nerve protein involved in multiple neuroprotective pathways. So far, the therapy has been tested in more than 1,600 people, and has been generally safe and well tolerated.
“The S1R has been shown to play a role in stimulating multiple neuroprotective pathways impaired in neurodegenerative diseases, such as ALS and Huntington’s disease,” said Paganoni.
Pridopidine was tested in an earlier Phase 2 trial (NCT04615923) that ran as part of HEALEY ALS (NCT04297683), a multi-arm study testing multiple treatments simultaneously against a shared placebo group.
Earlier trial results inform Phase 3 study design
This arm of HEALEY aimed to show that pridopidine could slow disease progression, as measured by the ALS Functional Rating Scale Revised (ALSFRS-R), after about six months, but it did not meet its main goal in the overall study population.
Still, data indicated that patients given pridopidine retained better speaking abilities than those given a placebo, and in a subgroup of people with rapidly progressive ALS who were within 18 months of symptom onset, pridopidine was associated with a significant 32% slowing of disease progression.
PREVAiLS aims to confirm those findings in a larger group of patients. Participants will be randomly assigned to receive either pridopidine or a placebo by mouth for 48 weeks (about 11 months), with three out of five participants receiving the active treatment. After this period, all may enter an open-label extension and receive pridopidine for another 48 weeks.
The trial’s main goal is to assess changes in ALSFRS-R scores adjusted for mortality. Secondary goals include survival, as well as changes in speech, lung function, and quality of life.
