Large trial tests whether a daily pill can slow fast-moving ALS

A large study is now enrolling people with ALS (amyotrophic lateral sclerosis) to test whether a pill called pridopidine can slow the disease. The trial, named PREVAiLS, plans to include 500 people whose ALS started recently and is getting worse quickly. It will check whether the drug slows the loss of everyday abilities and helps people live longer, compared with a placebo (a dummy pill)¹.

The design was described in an abstract presented at the 2026 Network of Excellence for ALS (NEALS) Annual Meeting, held October 27-30 in Clearwater, Florida, and reported by NeurologyLive on November 4¹. The trial is listed as recruiting on ClinicalTrials.gov, the US government’s public register of clinical studies².

What happened

PREVAiLS is a Phase 3 trial, the last large stage of testing usually needed before a drug can be considered for approval². It is randomized and double-blind, which means a computer decides who gets the drug and who gets the dummy pill, and neither the patients nor their doctors know which one each person is taking¹.

Pridopidine is an experimental pill made by Prilenia Therapeutics with its partner Ferrer. It works on a protein in cells called the sigma-1 receptor; the drug is designed to switch this receptor on¹. The trial will compare it against a dummy pill, with both groups also getting their standard care¹.

The study is led by Leonard H. van den Burg, a professor of neurology at University Medical Center Utrecht in the Netherlands, according to NeurologyLive¹. The US Food and Drug Administration (FDA) cleared the trial to go ahead in December 2025, and at that time it was planned to run at about 60 ALS treatment centers around the world¹.

How the trial works

Here is how the study is set up, based on the meeting report and the registry record:

• Who takes part: about 500 adults with early, rapidly progressing ALS¹. The registry lists the 500 figure as an estimate².
• The split: for every 3 people who get pridopidine, 2 get the dummy pill¹.
• How long: participants take their pill by mouth every day for 48 weeks. After that, everyone takes pridopidine for another 48 weeks². This second stage is “open-label,” meaning everyone knows they are on the drug¹.
• Check-ups: participants visit the clinic every one to three months for checks and tests².

The main measure is a standard ALS rating scale called the ALSFRS-R, which scores how well a person manages everyday functions. The trial will look at how much that score changes from the start to week 48, in a way that also takes deaths into account¹. The registry record lists the change through both week 26 and week 48².

The researchers will also track survival, speech, breathing, and “bulbar” function (the muscles used to speak and swallow), as well as quality of life using a 40-question ALS questionnaire called the ALSAQ-40¹. They will also look at blood markers such as neurofilament light, a protein released when nerve cells are damaged, and at patients’ own reports about how well they can communicate¹.

The evidence so far

PREVAiLS has no results yet. Its design rests on an earlier study: the HEALEY ALS Platform Trial, which tests several experimental ALS treatments side by side at many centers. Pridopidine was tested there as “Regimen D”¹³.

That earlier pridopidine study enrolled 163 people, started in December 2020, and finished collecting its main data in July 2022³. Its main goals were changes on the same ALSFRS-R rating scale and the death rate over 24 weeks³. It did not meet its primary goal¹.

Afterward, researchers looked at a smaller group within that trial: people with definite or probable ALS whose symptoms had started within the previous 18 months. This is called a post hoc analysis, meaning the group was chosen after the results were in¹. In that group, at 24 weeks:

• people on pridopidine had a slower decline in their overall ALSFRS-R score and in breathing function than those on the dummy pill¹;
• there was a trend toward a benefit in speaking and swallowing function that did not quite reach the usual statistical threshold¹;
• measures of speaking rate and articulation rate also favored the drug¹.

Median survival (the point by which half the group had died) was 600 days in people who started pridopidine early, compared with 300 days in people who started it later. That difference was not statistically significant, meaning it could have arisen by chance¹. Safety and side effects were described as comparable to the dummy pill¹.

What it does not show yet

The hints behind PREVAiLS come from a subgroup picked out after a trial that missed its main goal. Findings like this can point to a question worth asking, but they cannot show that a drug helps. When many smaller groups and measures are examined after the fact, some will look favorable by chance. PREVAiLS is designed to test the earlier findings prospectively, meaning the patient group and the measures were chosen before the trial began¹.

The survival numbers in particular need care. The 600-day versus 300-day figures compared people who started the drug early with people who started it later, and the gap was not statistically significant¹. Whether pridopidine changes survival is one of the questions the new trial is meant to answer.

There is also a small difference between the sources on how to describe the earlier study. NeurologyLive calls it a Phase 2 trial¹, while its registry record lists it as Phase 2/Phase 3³.

Who is behind it

Prilenia is listed as the sponsor of PREVAiLS², and the drug is being developed by Prilenia with Ferrer¹. The FDA clearance in December 2025 was announced by the two companies in a press release¹. The details reported this week come from a conference abstract, not a peer-reviewed paper¹.

The earlier HEALEY trial of pridopidine had a different sponsor: it is listed under Merit E. Cudkowicz, MD³. Its results were first posted on the registry in August 2023³.

How it fits the field

PREVAiLS is one of several ALS studies discussed around the 2026 NEALS meeting. NeurologyLive reported in the same week that another company outlined plans for a different late-stage ALS trial at the meeting, and that final safety and biomarker results were presented from a stopped gene-therapy trial for an inherited form of ALS¹.

The choice to focus on people with early, fast-moving disease follows directly from where the earlier trial showed its hints¹. If the drug does have an effect, testing it in the group where the signal appeared may give it the best chance to show up. If the earlier signal was chance, a large, carefully planned trial is the way to find that out.

What to watch next

• Enrollment: whether the trial reaches its planned 500 participants².
• Timing: the registry lists March 2028 as the expected date for finishing collection of the main data². Results would follow after that.
• The main answer: whether people on pridopidine lose everyday function more slowly over 48 weeks than people on the dummy pill, and whether survival differs¹.
• Longer follow-up: what happens in the 48-week stage when everyone takes the drug².

Biohack will follow this thread as the trial moves forward.