A recent Phase 2 trial investigating pridopidine for amyotrophic lateral sclerosis (ALS) has yielded promising results for specific patient subgroups, according to findings presented by Dr. Jeremy M. Shefner of the Barrow Neurological Institute.
The study, conducted as part of the innovative HEALEY platform trial, found that while pridopidine did not meet its primary endpoint across all participants, it showed meaningful efficacy signals in secondary outcomes and prespecified subgroups of ALS patients.
Trial Design and Primary Findings
Participants in the pridopidine arm of the HEALEY platform trial were randomized in a 3:1 ratio to receive either pridopidine or placebo for 24 weeks. The primary outcomes measured were changes in the ALS Functional Rating Scale-Revised (ALSFRS-R) total score and survival.
"While pridopidine was safe and well tolerated, there was no overall effect on the primary endpoint," Dr. Shefner explained during his presentation. However, he emphasized that the trial revealed "potentially meaningful signals suggesting efficacy in secondary endpoints, particularly measures of motor speech performance."
Promising Results in Specific Patient Subgroups
Notably, pridopidine demonstrated greater impact in participants with definite ALS and a baseline time from symptom onset of 18 months or less—a prespecified group characterized by rapid disease progression.
"The magnitude of the effects seen, as well as their consistency, add to the body of evidence suggesting that pridopidine may have an impact on patients with ALS," Dr. Shefner noted. These findings have supported the advancement of pridopidine to a Phase 3 study, which is currently being planned.
The HEALEY Platform Trial Approach
The HEALEY platform trial was developed specifically to address challenges in ALS clinical research. ALS, a degenerative disease affecting motor neurons in the brain and spinal cord, has an average survival of approximately four years after symptom onset, despite decades of clinical trials.
Dr. Shefner highlighted that traditional ALS trials face numerous obstacles: "The episodic nature of ALS requires new staffing and training for every trial; start-up is slow; participants wish to reduce placebo assignments as much as possible; and costs are excessive."
The platform trial approach offers several advantages, including:
- Reduction in the number of participants assigned to placebo groups
- Decreased time to complete studies
- Lower overall costs
- Broader inclusion criteria allowing more patients to participate
Since its inception in 2020, seven drugs have been evaluated through the HEALEY platform trial pipeline.
Current ALS Treatment Landscape
The presentation also addressed the current state of ALS treatment. Despite modest improvements in care, only two drugs have been approved by the FDA for ALS in the last decade. These approvals were based on small trials, and subsequent larger studies failed to meet primary endpoints, leading to one drug's withdrawal and reduced use of another.
"The average survival after the onset of the first ALS symptom is about 4 years – a small improvement despite decades of clinical trials," Dr. Shefner said. "Treatment modestly prolongs both survival, function, and quality of life for patients with ALS."
Patient Access and Trial Design Considerations
The HEALEY trial's inclusive design allows for a broader selection of participants than typical ALS studies, with disease onset up to 3 years and a minimal vital capacity of 50%. This approach was developed with patient access to experimental therapeutics in mind.
"Participants are drawn to this platform because there is a smaller chance that they'll receive a placebo," Dr. Shefner explained. However, he noted that this requires patients to be willing to receive any of the drugs being studied, which represents a different recruitment approach than traditional single-drug trials.
Future Directions
Based on the promising signals observed in the pridopidine arm, particularly in specific patient subgroups, researchers are now planning a Phase 3 study to further evaluate the drug's efficacy in ALS.
The HEALEY platform is designed to function as a perpetual trial, continuing to test promising compounds while maintaining a patient-friendly approach. This innovative model may help accelerate the development of effective treatments for ALS, a disease that affects approximately 1 in 700 men and has proven challenging to treat effectively.
