NeuroSense Reports Positive PARADIGM Trial Results Showing Slowed ALS Progression

NeuroSense Therapeutics Ltd. recently shared encouraging findings from its Phase 2b PARADIGM clinical trial focused on PrimeC, a treatment for high-risk ALS patients. The trial revealed that PrimeC significantly slowed disease progression by 43% compared to a placebo, indicating a 5.04-point advantage in the ALS Functional Rating Scale-Revised (ALSFRS-R) among those treated (p=0.02). This study targeted high-risk patients defined by the European Network for the Cure of ALS (ENCALS) as having a heightened risk for rapid disease progression, comprising roughly half of the ALS population.

These promising results were echoed by Jeremy M. Shefner, M.D., Ph.D., from the Barrow Neurological Institute, who highlighted PrimeC's potential to transform ALS treatment if it proceeds successfully through a Phase 3 trial. Newly diagnosed patients also experienced substantial benefits, with a 52% reduction in disease progression (p=0.008), translating to a 7.76-point difference in ALSFRS-R scores favoring PrimeC.

Further analyses in the Intent-to-treat (ITT) population showed high-risk ALS patients on PrimeC experienced a 31% decrease in disease progression (p=0.13). Additionally, newly diagnosed patients treated with PrimeC showed a 36% reduction in disease progression (p=0.14). Overall, these outcomes indicate PrimeC consistently outperforms placebo across various subgroups.

The subgroup analysis revealed specific benefits for patients with different disease durations. For those with up to 18 months of disease duration, PrimeC resulted in a 38% change (p=0.054), and for durations up to 24 months, a 37% symptom reduction was observed (p=0.047). Following these results, NeuroSense plans to use these insights to refine the design of its forthcoming pivotal trial to enhance its success and cost-effectiveness.

Alon Ben-Noon, CEO of NeuroSense, emphasized the significance of these findings as some of the most compelling in advanced ALS clinical trials. He expressed optimism about PrimeC’s potential impact on ALS patients, especially those in early stages of the disease.

Amyotrophic lateral sclerosis (ALS) is a severe, incurable neurodegenerative disorder leading to total paralysis and death within 2-5 years of diagnosis. Annually, over 5,000 individuals in the U.S. are diagnosed with ALS, contributing to a $1 billion disease burden. The ALS population is expected to grow by 24% by 2040 in the U.S. and EU.

The ALS Functional Rating Scale-Revised (ALSFRS-R) is the primary tool for tracking ALS progression, assessing 12 physical functions including speech, walking, and breathing. PrimeC aims to address ALS by combining ciprofloxacin and celecoxib, targeting motor neuron degeneration, inflammation, iron accumulation, and RNA regulation.

The Phase 2b PARADIGM trial involved 68 ALS patients across Canada, Italy, and Israel. Initial data from the trial's double-blind segment showed a 29% improvement in ALSFRS-R scores and a 13% improvement in forced vital capacity in favor of PrimeC. Most participants opted to continue with PrimeC through a 12-month open-label extension, underscoring their belief in its efficacy.

PrimeC is NeuroSense's leading drug candidate, designed to target multiple ALS mechanisms. It has shown safety and efficacy in previous trials and has been granted Orphan Drug Designation by both the U.S. FDA and the European Medicines Agency.

NeuroSense Therapeutics is dedicated to developing treatments for neurodegenerative diseases, including ALS, Alzheimer's, and Parkinson's. Their approach focuses on combined therapies targeting various disease pathways, driven by strong scientific research and biomarker analysis.