NAARDEN, NL and WALTHAM, Mass., 23 February 2023 --- Prilenia Therapeutics B.V., a clinical stage biotechnology company focused on the urgent mission to develop novel therapeutics to slow the progression of neurodegenerative and neurodevelopmental disorders, today announced initial results from the pridopidine arm of the Phase 2 HEALEY ALS Platform Trial. Pridopidine is an oral, small molecule, highly selective and potent Sigma-1 Receptor (S1R) agonist. It is an investigational drug, and its safety and efficacy have not been determined by the FDA.
While pridopidine did not meet the primary endpoint of change from baseline to week 24 in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), there were consistent, positive trends observed among participants receiving pridopidine across several pre-specified secondary and exploratory measures.
In post-hoc analyses, rapidly declining participants on pridopidine with definite or probable ALS who were early in the disease (less than 18 months from symptom onset) had substantially less decline in the ALSFRS-R total score (-7.51 points) compared to placebo (-12.71 points, unadjusted p-value=0.04).
Trends for less decline in the ALSFRS-R respiratory sub-scale were also seen in all participants (p=0.06). In pre-specified analyses of all study participants, benefits were observed in quantitative speech measures with significant improvement in speaking rate (p=0.028) and articulation rate (p=0.013).
Neurofilament light (NfL) is a well-recognized biomarker of ongoing neuronal injury that is increased in neurodegenerative diseases including ALS, Huntington’s disease (HD), multiple sclerosis, and Alzheimer’s disease. Pridopidine reduced NfL levels in rapidly declining patients with disease duration less than 18 months (average reduction of 40%) at 24 weeks compared to placebo in post-hoc analyses.
Data from this and other clinical studies show that pridopidine was well-tolerated, with a safety profile comparable to placebo. There were no new safety indicators as compared to previous clinical studies where pridopidine was similarly safe and well-tolerated.
“Pridopidine showed encouraging results for the potential treatment of ALS that deserve further exploration,” said Merit Cudkowicz, M.D., MSc, principal investigator and sponsor of the HEALEY ALS Platform Trial, Director of the Sean M. Healey & AMG Center for ALS, Chief of the Department of Neurology at Massachusetts General Hospital and the Julieanne Dorn Professor of Neurology at Harvard Medical School. “In particular, the impact of pridopidine on speech measures was notable, likely due to its S1R mechanism of action. Speech is a highly clinically relevant endpoint in ALS studies, and more than 80 percent of ALS patients become speech impaired, which significantly impacts their quality of life.”
“Pre-clinical data in mice and other species strongly indicated that S1R activity can mitigate the features of ALS and loss of function mutations in the Sigma-1 gene that cause ALS in humans. This study showed for the first time in humans that S1R agonism with pridopidine has the potential to impact ALS,” said Dr. Michael R. Hayden, CEO and Founder of Prilenia. “This study adds to the growing body of evidence that S1R activation has beneficial neuroprotective effects, and this gives us a compelling rationale for further development of pridopidine in ALS. Prilenia intends to continue its evaluation of pridopidine in ALS, and our future clinical program will build on the important learnings from the HEALEY ALS Platform Trial.”
Dr. Hayden continued, “We would like to extend our deepest appreciation to the team at the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital, the clinical trial investigators and staff at the Northeast ALS Consortium sites, and most importantly to the people living with ALS who participated in this trial and their families whose time and commitment made this research possible.”
Prilenia is exploring potential next steps for pridopidine in ALS. Additional analyses are underway, including from the open-label extension study, and complete study results will be presented at upcoming scientific meetings.