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Abstract Details

PrimeC, An Oral Candidate for Amyotrophic Lateral Sclerosis, Meets Primary Safety and Secondary End Points in the Phase 2b PARADIGM Trial
General Neurology
ES2 - Emerging Science 2 (5:30 PM-5:36 PM)
001

ALS is a complex disease with multiple pathological mechanisms requiring multi-factorial therapeutic approaches. PrimeC, a unique formulation of ciprofloxacin and celecoxib, is designed to synergistically target several key pathological mechanisms of ALS. In a previous Phase 2a trial, PrimeC demonstrated a favorable safety profile and trends toward slowing progression of functional and respiratory decline in ALS patients.

Assess the safety, tolerability and efficacy of PrimeC in patients with amyotrophic lateral sclerosis (ALS) in a randomized, placebo-controlled, double-blind, multi-centered Phase 2b trial (PARADIGM; NCT05357950).

69 participants were randomly assigned to receive PrimeC or placebo in a 2:1 ratio for 6 months. One patient was misdiagnosed with ALS and was excluded from the pre-defined analysis. Upon completion of the initial 6 months, participants were enrolled into a 12-month open-label-extension, during which all were administered with PrimeC, blinded for the original treatment allocation. Safety, ALSFRS-R, SVC, QoL, ALS associated biomarkers and survival were collected during the trial.

Safety outcomes did not differ significantly between treatment arms. In an Intended-To-Treat (ITT) analysis (n=68), the difference in the adjusted ALSFRS-R score between arms at 6 months was 29.2% (0.37 difference points/month; 95% CI, -0.1 to 0.84; p=0.12). In a Per-Protocol (PP) analysis (n=62), the mean rate of change was −0.9 points/month with PrimeC and −1.43 points/month with placebo (0.53 difference points/month; 95% CI, 0.05 to 1.01; p=0.03), showing a statistically significant difference of 37.4% between the two arms in 6-months of treatment. The adjusted SVC mean revealed a difference of 17.2% (p=0.39) in the PP dataset and 13.3% (p=0.5) in the ITT dataset.

These findings indicate that PrimeC is safe and may have a meaningful positive impact on ALS clinical outcomes. The data supports moving forward to a Phase 3 pivotal trial. Further analysis of biomarkers may provide additional support to the clinical results.

Authors/Disclosures
Merit E. Cudkowicz, MD, MSC, FAAN (Massachusetts General Hospital)
PRESENTER
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.
Adriano Chio, MD, FAAN (Dept. of Neuroscience, University of Turin) Dr. Chio has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cytokinetics. Dr. Chio has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi. Dr. Chio has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen.
No disclosure on file
Christen L. Shoesmith, MD, BSc, FAAN (University Hospital) An immediate family member of Dr. Shoesmith has received personal compensation for serving as an employee of Lundbeck . The institution of Dr. Shoesmith has received research support from AL-Pharma. The institution of Dr. Shoesmith has received research support from Mitsubishi Tanabe. The institution of Dr. Shoesmith has received research support from Cytokinetics. The institution of Dr. Shoesmith has received research support from Sanofi. Dr. Shoesmith has received personal compensation in the range of $0-$499 for serving as a Drug application review with CADTH (Government of Canada). Dr. Shoesmith has a non-compensated relationship as a Canadian ALS Research Consortium Chair with ALS Canada that is relevant to AAN interests or activities.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Ferenc Tracik (Neurosense Therapeutics) No disclosure on file
Jeremy M. Shefner, MD, PhD, FAAN (Barrow Neurological Institute) 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.
Vivian E. Drory, MD (Tel-Aviv Medical Center) Prof. Drory has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Prof. Drory has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amylyx. Prof. Drory has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Medison Pharma. The institution of Prof. Drory has received research support from Neurosense Therapeutics. The institution of Prof. Drory has received research support from AB Science. The institution of Prof. Drory has received research support from Biogen. The institution of Prof. Drory has received research support from Neuralight.