Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s Disease, is a devastating condition that gradually robs individuals of their ability to control muscle movement. It is a death sentence, typically claiming lives within two to five years of diagnosis. According to the ALS Association, approximately 5,000 Americans are diagnosed with this cruel ailment each year, equating to 15 new cases every day. 

While there are available treatments, they do little to halt the disease’s progression or meaningfully enhance the quality of life. However, NeuroSense Therapeutics Ltd.’s lead therapeutic candidate, PrimeC, offers a potentially more effective approach. 

PrimeC: A Potent Dual-Action Treatment for ALS 

PrimeC is unique in that it comprises specific dosages of two FDA-approved drugs, which work synergistically to target various facets of ALS. Celecoxib aims to reduce neuroinflammation, glutamate excitotoxicity, and oxidative stress, while Ciprofloxacin regulates microRNA synthesis and iron accumulation. 

In NeuroSense’s phase 2b trial of PrimeC, known as PARADIGM, the combined effect of these two drugs resulted in a 29.2% decline in disease progression and a 13.3% slowing of the loss of respiratory function. Even more impressively, the Per Protocol Population witnessed a statistically significant 37.4% decline in disease progression and a 17.2% slowing of the loss of respiratory function. The trial successfully met its primary endpoint of safety and tolerability, establishing a robust safety profile for PrimeC as it progresses toward commercialization. “I am excited by the top-line clinical data from PARADIGM. The clinical advancement of a new therapy that helps slow down the progression of ALS, with the potential to preserve quality of life, has the capacity to significantly positively impact people living with ALS and their families,” said Merit Cudkowicz, M.D., Chair of Neurology at Massachusetts General Hospital, the Director of the Healey & AMG Center for ALS, Julieanne Dorn Professor of Neurology at Harvard Medical School, and member of NeuroSense’s Scientific Advisory Board.

PrimeC Resonates With ALS Patients

The trial participants demonstrated a strong preference for PrimeC. Notably, 96% of those who completed the 6-month portion opted to continue PrimeC through a 12-month open-label extension. Furthermore, all participants who completed the 18-month trial treatment expressed a desire to continue taking PrimeC via an Investigator Initiated Trial.

PARADIGM, a prospective, multinational, randomized, double-blind, placebo-controlled trial, saw participation from individuals in Canada, Italy, and Israel. They were dosed for six months after being randomized 2:1 to receive PrimeC or placebo, respectively. 

The potency of PrimeC isn’t just observed by NeuroSense. An independent study conducted at the Ichida Stem Cell Lab at the University of Southern California found that PrimeC outperformed two FDA-approved ALS drugs and several other drugs in development in terms of improving motor neuron survival, reinforcing the drug’s potential.

Anticipated Milestones in 2024

In the year ahead, NeuroSense is gearing up for further milestones and developments, including findings from a strategic collaboration with Biogen Inc. BIIB. With results expected imminently, Biogen and NeuroSense are evaluating PrimeC’s impact on neurofilament levels in trial participants, a marker linked to ALS disease progression. Following the outcome, Biogen retains the right of first refusal to co-develop and commercialize PrimeC for ALS treatment for a limited time. This is a development that investors should monitor closely. 

The first half of 2024 is set to witness NeuroSense reporting primary endpoints of ALS hallmark biomarkers, TDP-43 and ProstaglandinJ2, to evaluate PrimeC’s biological activity and target engagement. “The magnitude of this apparent improvement is especially noteworthy considering the natural history of ongoing disease progression. Furthermore, the most exciting aspects of these data include not only the statistical differences in ALSFRS-R score at the specified timepoints, but also that the improved trajectory of the ALSFRS-R decline was evident from the earliest timepoint, throughout the entire study period,” said Jeffrey Rosenfeld, MD, PhD, Professor of Neurology at Loma Linda University and member of NeuroSense’s Scientific Advisory Board. “The complexity of ALS pathology warrants a multi-drug therapeutic strategy and it is especially gratifying to see this combination therapy advance.”

Next in line for PrimeC is a phase 3 trial, paving the way for potential marketing approval. To facilitate this process, NeuroSense anticipates End of Phase 2 meetings with the FDA and the European Medicines Agency in the second quarter of 2024. Additionally, the company is in discussions with several leading pharmaceutical firms specializing in central nervous system therapeutics to explore potential strategic partnerships and business opportunities.

“The clinical efficacy observed in the top-line PARADIGM trial results underscores PrimeC’s potential to provide a significant and meaningful clinical benefit to people grappling with ALS, as any slowdown in the progression of this incurable disease holds significance from both a clinical and patient standpoint,” said Alon Ben-Noon, CEO of NeuroSense. “This is perhaps one of the most significant outcomes seen to date. We believe that these data, along with the anticipated correlative neurofilament readouts this month, could lead to a strategic partnership and an expedited regulatory pathway for PrimeC’s journey to the market.”

Featured photo by Milad Fakurian on Unsplash.

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