2025 American Academy of Neurology Abstract Website

Michal Geva¹, Jeremy Shefner², Bjorn Oskarsson³, Rachel G. Lichtenstein⁴, May Meltzer¹, Yael Cohen¹, Randal Hand¹, Kelly Chen¹, Melanie Leitner⁵, Sabrina Paganoni⁶, Merit Cudkowicz⁶, Michael Hayden⁷
¹Prilenia Therapeutics, ²Barrow Neurological Institute, ³Mayo Clinic, ⁴Ben-Gurion University of the Negev, ⁵Accelerating NeuroVentures, LLC, ⁶Massachusetts General Hospital, ⁷Prilenia Therapeutics and University of British Columbia

Objective:

Pridopidine 45mg (bid) was evaluated in the Ph2 HEALEY ALS Platform Trial.

Background:

Pridopidine, a S1R agonist, demonstrates neuroprotective effects by improving cellular pathways impaired in ALS including ER stress. Pridopidine (1µM) reduced parameters of ER stress including expression of BiP (72% reduction, p<0.0001) and CHOP (50% reduction, p<0.0001) and increased cell viability by 69% (p<0.0001). Rare mutations in S1R cause ALS.

Design/Methods:

A post hoc analysis was performed of El Escorial definite+probable ALS and early (symptom onset <18mo) subjects. Endpoints include change from baseline to 24 weeks in ALSFRS-R, and measures of respiration, bulbar, speech, and quality-of-life (QoL).

Results:

Pridopidine was well tolerated, consistent with its prior safety profile.

Pridopidine (n=37) shows 32% slowing of decline vs placebo (n=35) in ALSFRS-R (wk24 Δ2.9, p=0.03). Benefits are observed in ALSFRS-R respiratory (wk24 Δ1.20, p=0.03), and bulbar (wk24 Δ0.93, p=0.06) domains. Pridopidine shows no worsening in dyspnea (wk24 Δ0.62, p=0.04). Benefits in speaking rate (Δ0.39, p=0.005) and articulation rate (Δ0.40, p=0.002) are observed. Pridopidine shows less decline in QoL (ALSAQ-40 Δ-10.83, p=0.018), notably in eating & drinking (Δ-19.18, p=0.015) and communication (Δ-13.03, p=0.12) subdomains.

A Kaplan-Meier survival analysis shows a prolongation of median survival time (~300 to 600 days) compared to the delayed-start (168 days) placebo-to-pridopidine participants (n=12)(log rank p=0.069). The Cox Proportional Hazard Ratio (HR), adjusted for baseline characteristics is 0.429 (p=0.052).

Conclusions:

Pridopidine demonstrated beneficial effects across multiple clinical measures of ALS, including survival benefits in definite+probable ALS and early participants. These encouraging observations support and inform planning for a Ph3 study.