Phase 3 ALS Trial Launches for Pridopidine as AI Identifies Potential Drug Candidates

A phase 3 clinical trial has launched to evaluate the investigational drug pridopidine as a potential treatment for amyotrophic lateral sclerosis (ALS), while separate research using artificial intelligence has identified existing FDA-approved drugs that may extend survival for patients. The PREVAiLS study, believed to be the only currently recruiting phase 3 ALS trial, has enrolled its first participant and aims to evaluate the safety and effectiveness of pridopidine in slowing disease progression in early, rapidly progressive patients.

The global clinical trial will include 500 participants across up to 60 ALS treatment centers in 13 countries. Pridopidine is a sigma-1 receptor (S1R) agonist, which has been shown to play a role in stimulating multiple neuroprotective pathways impaired in neurodegenerative diseases like ALS and Huntington's disease. This phase 3 study follows phase 2 HEALEY ALS Platform Trial results in 2023, which did not reach its main goal of slowing ALS function over 24 weeks but showed positive results in a subgroup of patients who were early in disease and declining rapidly.

In the HEALEY trial, the drug was generally well-tolerated, with a safety profile similar to placebo. The most common adverse events were falls and muscle weakness, which overlap with ALS symptoms. Phase 3 incorporates "key learnings" from phase 2 and is expected to determine whether pridopidine is effective as a potential treatment for the disease.

Separately, researchers have used artificial intelligence to identify 18 FDA-approved drugs that could potentially improve outcomes for people with ALS. The study analyzed health records of over 11,000 ALS patients from the U.S. Department of Veterans Affairs between 2009 and 2020 and identified three classes of existing drugs - statins, type-5 phosphodiesterases, and alpha-blockers - that showed a positive association with longer survival in ALS patients. The study was published in the medical journal The Lancet in March 2026.

In another development, scientists have found a promising triple drug combination for sporadic ALS using newly developed cell models. The combination includes riluzole (which is already approved for ALS as Tiglutik and generics), baricitinib, and memantine. The researchers created cell-based models from motor neurons derived from people with sporadic ALS and tested 107 drugs that had been previously evaluated in clinical trials for ALS. The study, published in the journal Nature Neuroscience, found that nearly all drugs tested (97%) failed to improve motor neuron health, but the three-drug combination demonstrated efficacy.

ALS is a progressive disease in which the brain loses connection with the muscles, slowly stripping away a person's ability to walk, talk, eat, dress, write, swallow and, eventually, breathe. The disease typically proves fatal within 3-5 years of diagnosis, with about 20% of patients living five years or longer. Diagnosis typically occurs between ages 40 and 70, and while the disease affects motor neurons controlling voluntary movement, the five senses, eye muscles, and bladder control are not affected.

The insights gained from the phase 3 trial will be critical in determining whether early signals from phase 2 translate into meaningful, consistent benefits for people with early, rapidly progressing ALS. Researchers stressed that further testing on broader data sets will be necessary to confirm the AI findings, and clinical trials on the identified drugs are the next step to determine if they can truly extend survival for ALS patients.