Abstract Details

Title Pridopidine for the Treatment of ALS–Improvements in the Subgroup of Definite, Probable, and Early (<18mo from Onset) Subjects in the Phase 2 Healey ALS Platform Trial

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S5 - Updates on Amyotrophic Lateral Sclerosis (5:18 PM-5:30 PM)

Poster/Presentation
Number 010

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.

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

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.

Authors/Disclosures
Merit E. Cudkowicz, MD, MSC, FAAN (Massachusetts General Hospital) PRESENTER	Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for biogen. Dr. Cudkowicz has received personal compensation in the range of $0-$499 for serving as a Consultant for cytokinetics. Dr. Cudkowicz has received personal compensation in the range of $0-$499 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 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 $500-$4,999 for serving as a Consultant for vectorY. 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 novartis. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 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 $500-$4,999 for serving as a Consultant for ac immune. Dr. Cudkowicz has received personal compensation in the range of $0-$499 for serving as a Consultant for pontifax. 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 $0-$499 for serving as a Consultant for ab science. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for aclipse. Dr. Cudkowicz has received personal compensation in the range of $5,000-$9,999 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 . The institution of Dr. Cudkowicz has received research support from NINDS. 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. The institution of Dr. Cudkowicz has received research support from PharmAust. The institution of Dr. Cudkowicz has received research support from woolsley. Dr. Cudkowicz has received research support from lilly. The institution of Dr. Cudkowicz has received research support from J& J. Dr. Cudkowicz has received publishing royalties from a publication relating to health care.
Michal Geva (Prilenia Therapeutics)	Michal Geva has received personal compensation for serving as an employee of Prilenia Therapeutics. Michal Geva has received intellectual property interests from a discovery or technology relating to health care.
Jeremy M. Shefner, MD, PhD, FAAN (Barrow Neurological Institute)	Dr. Shefner has received personal compensation in the range of $500-$4,999 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 $500-$4,999 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 $0-$499 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 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 $5,000-$9,999 for serving as a Consultant for Neuvivo. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nura BIo. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prilenia. Dr. Shefner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for swanbio. Dr. Shefner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for vertex. 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 Argenx. 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 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. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a grant review chair with DOD- General Dynamics.
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.
Rachel G. Lichtenstein, PhD	Dr. Lichtenstein has nothing to disclose.
May Meltzer, PhD	Mrs. Meltzer has nothing to disclose.
Yael Cohen	Yael Cohen has nothing to disclose.
Randal Hand (Prilenia Therapeutics)	Dr. Hand has received personal compensation for serving as an employee of Prilenia Therapeutics.
Kelly Chen	Kelly Chen has received personal compensation for serving as an employee of Prilenia Therapeutics.
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.
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.
Michael Hayden	Michael Hayden has received personal compensation for serving as an employee of Prilenia Therapeutics. Michael Hayden has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CAMP4. Michael Hayden 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 AbCellera Biologics Inc.. Michael Hayden 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 Ionis Pharmaceuticals . Michael Hayden has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for 89 Bio. Michael Hayden 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 Oxford Biomedica . Michael Hayden has stock in Ionis Pharmaceuticals. Michael Hayden has stock in AbCellera Biologics Inc.. Michael Hayden has stock in 89 Bio. The institution of Michael Hayden has received research support from Canadian Institutes of Health Research. The institution of Michael Hayden has received research support from National Research Council Canada. The institution of Michael Hayden has received research support from Huntington Society of Canada. The institution of Michael Hayden has received research support from Bev Hartig Huntington Disease Foundation. Michael Hayden has received intellectual property interests from a discovery or technology relating to health care. Michael Hayden has received intellectual property interests from a discovery or technology relating to health care. Michael Hayden has received intellectual property interests from a discovery or technology relating to health care. Michael Hayden has received intellectual property interests from a discovery or technology relating to health care. Michael Hayden has received intellectual property interests from a discovery or technology relating to health care. Michael Hayden has received intellectual property interests from a discovery or technology relating to health care. Michael Hayden has received intellectual property interests from a discovery or technology relating to health care. Michael Hayden has received intellectual property interests from a discovery or technology relating to health care. Michael Hayden has received intellectual property interests from a discovery or technology relating to health care. Michael Hayden has received intellectual property interests from a discovery or technology relating to health care.

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