Pridopidine for the Treatment of ALS—Results from the Phase 2 Healey ALS Platform Trial (S5.003)

Abstract

Objective: Pridopidine was evaluated in the Phase 2 HEALEY ALS Platform Trial. Background: Pridopidine is an oral small molecule and potent sigma‐1 receptor agonist. Design/Methods: Eligible participants had El Escorial possible, probable, or definite ALS, symptom onset <36mo and vital capacity >50%‐ predicted. Pridopidine 45mg bid (n=121) was compared to a shared placebo (n=164). Primary endpoint was change from baseline through 24 weeks in ALSFRS‐R total (Full Analysis Set, FAS). Secondary and exploratory endpoints included speech, respiration, and quality of life measurements. Prespecified and post‐hoc subgroups included definite+probable ALS, early (<18mo symptom onset) and fast progressors (prebaseline slope <0.0001 and articulation rate (Δ1.03, p<0.0001). In definite ALS and early participants, pridopidine trended favorably in ALSFRS‐R progression (Δ2.4, p=0.19) and respiratory domain (Δ1.04, p=0.18), and improved in dyspnea (Δ1.35, p=0.014). Definite+probable ALS, early and fast progressors showed a greater improvement in ALSFRS‐R (Δ5.2, p=0.04). Less decline on the ALSAQ‐40 quality of life scale (Δ ‐10.83, p=0.018), in eating & drinking (Δ‐19.18, p=0.015) and a trend in communication (Δ‐13.04, p=0.12) were seen in definite ALS and early participants. A Kaplan‐Meier survival analysis showed a prolongation of median survival time, from ∼300 to 600 days in definite+probable ALS and early participants (n=37) compared to the delayed‐start (168 days) placebo participants (n=12) (log rank test: p=0.069). Conclusions: Beneficial effects of pridopidine were observed in speech (FAS) and multiple measures of disease progression (post‐hoc subgroups). This includes an increase in survival time for definite+probable ALS & early participants. These observations inform the ongoing planning for a Phase 3 study.