Abstract Details

Title Pridopidine for the Treatment of ALS—Results from the Phase 2 Healey ALS Platform Trial

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S5 - ALS and CMT: New Therapeutic Approaches (3:54 PM-4:06 PM)

Poster/Presentation
Number 003

Background

Pridopidine is an oral small molecule and potent sigma-1 receptor agonist.

Objective Pridopidine was evaluated in the Phase 2 HEALEY ALS Platform Trial.

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<-1). Nominal p-values are reported.

Results

Pridopidine was well tolerated, consistent with prior safety profile. Primary endpoint was not met in the FAS. Significant speech improvements were observed in the FAS, and post-hoc analysis of definite+probable ALS, early and fast progressors (pridopidine n=20; placebo n=14), showed a greater improvement in speaking rate (Δ1.08, p<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.

Authors/Disclosures
Jeremy M. Shefner, MD, PhD, FAAN (Barrow Neurological Institute) PRESENTER	Dr. Shefner has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amylyx. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Uniqure. Dr. Shefner has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Clene. Dr. Shefner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Cytokinetics. Dr. Shefner has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Mitsubishi Tanabe Pharma America. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for annexon. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for SwanBio. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vertex. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurosense. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for swanbio. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for vertex. Dr. Shefner has received personal compensation in the range of $50,000-$99,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for UpToDate. The institution of Dr. Shefner has received research support from NIH. The institution of Dr. Shefner has received research support from Mitsubishi Tanabe Pharma America. The institution of Dr. Shefner has received research support from ALS Association. The institution of Dr. Shefner has received research support from Amylyx. The institution of Dr. Shefner has received research support from BIogen. The institution of Dr. Shefner has received research support from Cytokinetics. The institution of Dr. Shefner has received research support from IONIS. The institution of Dr. Shefner has received research support from Healey Center for ALS.
Bjorn E. Oskarsson, MD, FAAN (Mayo Clinic)	Dr. Oskarsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amylyx. The institution of Dr. Oskarsson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Oskarsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AnnJi. The institution of Dr. Oskarsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi. Dr. Oskarsson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Tsumura. The institution of Dr. Oskarsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MediciNova. The institution of Dr. Oskarsson has received research support from Biogen. The institution of Dr. Oskarsson has received research support from Medicinova. The institution of Dr. Oskarsson has received research support from Cytokinetics. The institution of Dr. Oskarsson has received research support from Calico. The institution of Dr. Oskarsson has received research support from Mitsubishi. The institution of Dr. Oskarsson has received research support from Tsumura. The institution of Dr. Oskarsson has received research support from Sanofi. The institution of Dr. Oskarsson has received research support from AZTherapeutics. The institution of Dr. Oskarsson has received research support from Orion. The institution of Dr. Oskarsson has received research support from Esaii.
Yael Cohen	Yael Cohen has nothing to disclose.
Kelly Chen	No disclosure on file
Melanie Leitner, PhD (Accelerating NeuroVentures, LLC)	Dr. Leitner has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Prilenia. Dr. Leitner has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for ALS Investment Fund. Dr. Leitner has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Fundamental Pharma. Dr. Leitner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Caraway. Dr. Leitner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Affinia Therapeutics. Dr. Leitner has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Jannsen. Dr. Leitner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Tolerion/Alpha-5 Integrin. Dr. Leitner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Verge Genomics. Dr. Leitner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Tranquis. Dr. Leitner has stock in Bristol Myers Squibb. Dr. Leitner has stock in Editas. Dr. Leitner has stock in Provention Bio. Dr. Leitner has stock in Sanofi. Dr. Leitner has stock in Vertex. Dr. Leitner has stock in GSK. Dr. Leitner has stock in Eledon. Dr. Leitner has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant with ALS Finding a Cure. Dr. Leitner has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant with Charley's Fund.
James D. Berry, MD MPH (Massachusetts General Hospital)	Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Clene Nanomedicine. Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MT Pharma Holdings of America. Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Regeneron. Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MTPA. Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Berry has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Berry has stock in ReactNeuro. The institution of Dr. Berry has received research support from Biogen. The institution of Dr. Berry has received research support from MT Pharma of America. The institution of Dr. Berry has received research support from Rapa Therapeutics. The institution of Dr. Berry has received research support from Brainstorm Cell Therapeutics. The institution of Dr. Berry has received research support from Alexion. The institution of Dr. Berry has received research support from nQ Medical. The institution of Dr. Berry has received research support from ALSA. The institution of Dr. Berry has received research support from MDA. The institution of Dr. Berry has received research support from Amylyx. The institution of Dr. Berry has received research support from Transposon. Dr. Berry has a non-compensated relationship as a Scientific Advisor with Everything ALS that is relevant to AAN interests or activities.
Eric A. Macklin, PhD (Massachusetts General Hospital)	The institution of Dr. Macklin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AI Therapeutics. Dr. Macklin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Chase Therapeutics. Dr. Macklin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bial Biotech. Dr. Macklin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Macklin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Stoparkinson Healthcare LLC. Dr. Macklin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Macklin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Macklin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. The institution of Dr. Macklin has received research support from Biohaven. The institution of Dr. Macklin has received research support from Clene Nanomedicine. The institution of Dr. Macklin has received research support from Mitsubishi Tanabe Pharmaceuticals America. The institution of Dr. Macklin has received research support from Prilenia. The institution of Dr. Macklin has received research support from UCB Ra Pharma. The institution of Dr. Macklin has received research support from Revalesio. The institution of Dr. Macklin has received research support from Seelos. The institution of Dr. Macklin has received research support from Calico. The institution of Dr. Macklin has received research support from Denali. The institution of Dr. Macklin has received research support from NeuroDex. The institution of Dr. Macklin has received research support from Alector. The institution of Dr. Macklin has received research support from ITB-Med.
Lori Chibnik	No disclosure on file
Lindsay Pothier (Massachusetts General Hospital)	No disclosure on file
Michal Geva (Prilenia Therapeutics)	No disclosure on file
Paul Goldberg	Paul Goldberg has received personal compensation for serving as an employee of Prilenia. Paul Goldberg has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Ionis Pharmaceuticals. Paul Goldberg has stock in Prilenia.
Michael Hayden	No disclosure on file
Sabrina Paganoni, MD, PhD	Dr. Paganoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cytokinetics. Dr. Paganoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jannsen. Dr. Paganoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arrowhead. Dr. Paganoni has received personal compensation in the range of $0-$499 for serving as a Consultant for Sola. Dr. Paganoni has received personal compensation in the range of $0-$499 for serving as a Consultant for Frequency Therapeutics. The institution of Dr. Paganoni has received research support from Amylyx. The institution of Dr. Paganoni has received research support from Revalesio. The institution of Dr. Paganoni has received research support from Alector. The institution of Dr. Paganoni has received research support from UCB. The institution of Dr. Paganoni has received research support from Biohaven. The institution of Dr. Paganoni has received research support from Clene. The institution of Dr. Paganoni has received research support from Prilenia. The institution of Dr. Paganoni has received research support from Seelos. The institution of Dr. Paganoni has received research support from Calico. The institution of Dr. Paganoni has received research support from Denali. The institution of Dr. Paganoni has received research support from Anelixis. The institution of Dr. Paganoni has received research support from Cytokinetics.
Merit E. Cudkowicz, MD, MSC, FAAN (Massachusetts General Hospital)	Dr. Cudkowicz has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for biogen. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for cytokinetics. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for immunitypharm. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for denali. The institution of Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for wave. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for transposon. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Quralis. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Regeneron. Dr. Cudkowicz has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neurosense. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for vectorY. Dr. Cudkowicz has received personal compensation in the range of $0-$499 for serving as a Consultant for Arrowhead. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Servier. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eledon. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for inflectis. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for roche. Dr. Cudkowicz has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for novartis. Dr. Cudkowicz has received personal compensation in the range of $0-$499 for serving as a Consultant for ono. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for otsuka. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for coya. Dr. Cudkowicz has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Locust Walk. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pasithea. Dr. Cudkowicz has received personal compensation in the range of $50,000-$99,999 for serving as an officer or member of the Board of Directors for Praxis Precision Medicine. Dr. Cudkowicz has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Annals of Neurology . An immediate family member of Dr. Cudkowicz has stock in Sqz. The institution of Dr. Cudkowicz has received research support from NINDS. The institution of Dr. Cudkowicz has received research support from ALSA . The institution of Dr. Cudkowicz has received research support from ALSFAC. The institution of Dr. Cudkowicz has received research support from UCB ra. The institution of Dr. Cudkowicz has received research support from Biohaven. The institution of Dr. Cudkowicz has received research support from Clene nanomedicine. The institution of Dr. Cudkowicz has received research support from prilenia. The institution of Dr. Cudkowicz has received research support from ALS one. The institution of Dr. Cudkowicz has received research support from Seelos. The institution of Dr. Cudkowicz has received research support from Calico. The institution of Dr. Cudkowicz has received research support from denali. The institution of Dr. Cudkowicz has received research support from ITB. Dr. Cudkowicz has received publishing royalties from a publication relating to health care.