On March 30, 2026, the first participant was enrolled in the PREVAiLS trial at Mass General Brigham, under the supervision of Sabrina Paganoni, MD, PhD. PREVAiLS is a global Phase 3 study testing whether pridopidine, a drug that activates a specific protein involved in nerve cell survival, can slow the progression of ALS in patients who are early in their disease and declining quickly.
ALS is a disease that takes a lot, and it takes it fast. The brain gradually loses its connection to the muscles that control movement, speech, swallowing, and eventually breathing. Most people live 3 to 5 years after diagnosis. According to CDC estimates, about 33,000 people in the U.S. were living with ALS in 2022, and that number is projected to rise past 36,000 by 2030 as the population ages.
The loss of actor Eric Dane to ALS in February 2026, less than a year after he announced his diagnosis in April 2025, brought renewed public attention to how aggressive this disease can be and how limited the current options are. His advocacy in the months before his passing helped put a spotlight on the urgent need for research. Against that backdrop, the launch of PREVAiLS carries real weight.
How Pridopidine Works as an ALS Treatment
A different approach than existing ALS treatments
Pridopidine works by activating something called the sigma-1 receptor (S1R), a protein found on the surface of structures inside cells. This receptor acts as a kind of maintenance switch for nerve cells. When it is turned on, it supports several processes that keep neurons healthy: managing cellular stress, maintaining energy production in mitochondria, clearing out toxic protein buildup, and supporting the release of growth factors that protect nerve connections.
In simpler terms, pridopidine is designed to help motor neurons survive longer by supporting their internal repair systems. That is a different strategy from the drugs currently available. Riluzole works by reducing excess glutamate signaling. Edaravone targets oxidative stress. Tofersen (for the small subset of patients with SOD1 mutations) works at the genetic level. Pridopidine goes after the cellular machinery itself.
Pridopidine Phase 2 ALS Trial Results
Pridopidine was tested in the HEALEY ALS Platform Trial, a large multi-drug study run out of Massachusetts General Hospital. In the overall population, the drug did not hit its primary endpoint of slowing functional decline over 24 weeks. That was disappointing.
Researchers then looked more closely at one group of patients. Among 72 people who were early in their disease (within 18 months of symptom onset), had definite or probable ALS and were declining rapidly, those on pridopidine showed slower decline than those on placebo. These were post hoc results with nominal p values, so they suggest an effect but do not prove one. In that subgroup analysis, respiratory decline slowed by 62%. Articulation rate decline was reduced by 93%. Speaking rate decline dropped by 70%. The drug also showed improvements in a breathlessness measure, with dyspnea improving by 88% in this subgroup.
Safety was encouraging throughout. The drug was well-tolerated with a profile similar to placebo. The most reported side effects were falls and muscle weakness, both of which overlap with ALS symptoms themselves rather than indicating drug-related problems.
What Changed in the Pridopidine Phase 3 Trial Design
The Phase 2 results shaped the design of PREVAiLS in important ways. Rather than enrolling a broad cross-section of ALS patients, the Phase 3 trial is specifically targeting adults who are early in their disease (within 18 months of symptom onset) and progressing rapidly. That is the population where the strongest signals appeared.
The study is also longer. Phase 2 ran for 24 weeks. PREVAiLS has a 48-week double-blind treatment period followed by a 48-week open-label extension, giving researchers much more time to observe whether the drug has a real and lasting effect.
When it launched, Prilenia described PREVAiLS as the only Phase 3 ALS trial recruiting, but ClinicalTrials.gov also lists other recruiting late-stage ALS studies, including a Phase 3 trial of masitinib. As of late September 2026, ClinicalTrials.gov lists 55 PREVAiLS sites in 13 countries, 54 of them recruiting, across the U.S., Canada, Europe, the UK and Israel.
The Current ALS Treatment Landscape
For context, here is where things stand with approved ALS treatments. The options are limited and the benefits are modest.
Riluzole was approved in 1995 and remains the baseline standard. It extends median survival by about 2 to 3 months but does not reverse nerve damage or stop progression. Edaravone (Radicava), approved in 2017, targets oxidative stress and may slow functional decline in some patients. Tofersen (Qalsody), approved in 2023, is the first gene-targeted ALS therapy, but it only applies to the roughly 2% of patients with SOD1 mutations. AMX0035 (Relyvrio) was approved in 2022 but was voluntarily withdrawn from the market after its Phase 3 confirmatory trial failed to show benefit.
That is the reality: a 30-year-old drug that buys 2 to 3 months, a free radical scavenger, a gene therapy for a tiny fraction of patients, and a withdrawn drug. For the vast majority of people with ALS, the treatment picture has not changed much in a generation. That is why new approaches like pridopidine are so important, even when the path to approval is long and uncertain.
What ALS Patients and Families Should Know About Pridopidine
PREVAiLS is open to adults aged 18 to 80 with definite or probable ALS whose symptoms started within the last 18 months, who still have at least 60% of expected breathing capacity (slow vital capacity), and whose predicted rate of progression on a standard risk calculator (TRICALS) falls in the trial's fast-progressing range. The trial is taking place at up to 60 ALS treatment centers across 13 countries. Information about participating sites and eligibility is available through the Prilenia website and through ClinicalTrials.gov.
Every person who enrolls in a trial helps generate the evidence needed to bring treatments forward, not just for themselves but for everyone who comes after them.
“The earlier we can diagnose and treat ALS, the greater the potential to preserve function and maintain quality of life for longer.”
Kuldip Dave, PhD, SVP of Research, The ALS Association
Definitive conclusions will not be available until PREVAiLS is completed and fully analyzed. But for a disease where the treatment options have barely changed in 30 years, the fact that a carefully designed Phase 3 trial is now enrolling, built on real signals from Phase 2, is a development worth paying attention to.
Quick Reference: ALS by the Numbers
ALS mainly affects the motor neurons that control voluntary movement and breathing. Most people keep their ability to reason, remember and understand, although some develop problems with language or decision-making, and some develop a form of dementia (FTD-ALS). Many people with ALS remain mentally sharp and aware throughout their illness, which is part of what makes the disease so difficult. The mind stays present while the body progressively loses its ability to act.