NeuroSense Therapeutics Ltd. (Nasdaq: NRSN) (“NeuroSense”), a company developing treatments for severe neurodegenerative diseases, today reported additional positive efficacy data from further evaluation of its Phase 2b trial (PARADIGM) with NeuroSense’s lead drug candidate for amyotrophic lateral sclerosis (“ALS”), PrimeC.
Evaluation of the pre-specified Per Protocol (PP) population analysis of the recent top-line results from PARADIGM revealed a statistically significant slowing of disease progression with a 37.4% (p=0.03) difference in the gold standard ALS tracking measure, the ALS Functional Rating Scale-Revised (“ALSFRS-R”), in favor of PrimeC vs placebo, and 17.2% (p=0.39) difference in Slow Vital Capacity (“SVC”), in favor of PrimeC vs placebo. The PP analysis population includes all participants who adhered to the trial protocol and treatment plan without any major protocol deviations. The goal of a PP analysis in clinical trials is to assess the efficacy of a treatment under optimal conditions, thereby providing a clearer understanding of how well the treatment works when implemented as intended, contributing to a more comprehensive view of the trial results. PARADIGM’s PP population analysis is pre-defined in the trial’s statistical analysis plan, which includes 62 patients (43 active and 19 placebo) compared to 68 patients in the Intent to Treat (ITT) population (45 active and 23 placebo).
PARADIGM is a prospective, multinational, randomized, double-blind, placebo-controlled Phase 2b (NCT05357950) clinical trial. The trial’s primary endpoints include: safety and tolerability, and ALS-related biomarkers TDP-43 and Prostagladin2. The trial’s secondary endpoints include: clinical efficacy outcome measures, ALSFRS-R and SVC. ALSFRS-R is the most widely used ALS tracking tool accepted by the FDA, utilized by neurologists treating ALS patients, in clinical trials, and by other regulators to determine disease progression. It tracks 12 changes in a person’s physical abilities over time including functions such as: speech, walking, climbing stairs, dressing/hygiene, handwriting, turning in bed, cutting food, salivation, swallowing, and breathing. SVC is a measurement of respiratory function.
While PARADIGM is powered to demonstrate statistically significant changes in the trial’s primary endpoints, the highly favorable clinical results seen in the PP analysis achieved an unexpected statistical significance.
The new data reported today comes on the heels of recent positive top-line safety and efficacy data of PARADIGM announced by NeuroSense. An analysis of the ITT top-line data from the 6-month double-blind segment of the trial showed clinically meaningful signs of efficacy with a 29% difference in ALSFRS-R (p=0.12) and a 13% difference in SVC (p=0.5), both in favor of PrimeC vs placebo. These data include all 68 people living with ALS enrolled in Canada, Italy, and Israel, with the exclusion of one patient who was misdiagnosed. Most patients enrolled in both the active and placebo arms of trial were concurrently treated with Riluzole, the ALS standard of care medication, indicating PrimeC slowed disease progression well beyond the level afforded by the FDA approved ALS drug.
In addition, the trial met its primary endpoint of safety and tolerability with results comparable to placebo, establishing a solid safety profile for PrimeC. 96% of the trial participants who completed the 6-month double-blind portion of the trial chose to receive treatment with PrimeC through a 12-month open label extension. Furthermore, to date, all participants that completed the 18-month trial treatment duration requested to continue taking PrimeC, which is provided to them via an Investigator Initiated Trial.
NeuroSense expects to report results from a strategic collaboration with Biogen in January 2024, evaluating the impact of PrimeC on neurofilament levels in participants enrolled in PARADIGM. Upon receipt of results, Biogen has the right of first refusal to co-develop/ commercialize PrimeC for the treatment of ALS for a limited time following the results. The Company expects to report primary biomarker endpoints of ALS hallmarks TDP-43 and Prostagladin2, to evaluate PrimeC’s biological activity and target engagement, in the first half of 2024 following the completion of the analysis of participants’ plasma.
An End of Phase 2 meeting with the FDA and a Scientific Advice meeting with European Medicines Agency (EMA) to discuss these results and to determine the best path forward for PrimeC’s development is expected in the first half of 2024.
“As we analyze the PARADIGM trial results, we continue to gain a better understanding of PrimeC’s potential to render a significant and meaningful clinical benefit to people living with ALS. Today we are eager to share these new data with the ALS community, as we believe the PP analysis, demonstrating a statistically significant 37.4% difference in ALSFRS-R in patients treated with PrimeC vs. placebo, is an exceptional result,” stated Alon Ben-Noon, NeuroSense’s CEO. “This data, in conjunction with hopefully correlative neurofilament readouts, will create a regulatory opportunity to advance PrimeC’s development in a breakthrough manner toward the market.”
About ALS
Amyotrophic lateral sclerosis (“ALS”) is an incurable neurodegenerative disease that causes complete paralysis and death within 2-5 years from diagnosis. Every year, more than 5,000 patients are diagnosed with ALS in the U.S. alone, with an annual disease burden of $1 billion. The number of patients with ALS is expected to grow by 24% by 2040 in the U.S. and EU.
