Investigational PrimeC Improves Complication-Free Survival in PARADIGM Study of ALS

Jeremy M. Shefner, MD, PhD

Weeks after NeuroSense announced positive data from the phase 2b PARADIGM trial (NCT05357950), newly announced analyses revealed that treatment with investigational PrimeC resulted in enhanced complication-free survival over placebo in patients with amyotrophic lateral sclerosis (ALS) across a 12-month period. The company plans to submit these results to regulatory agencies, including the FDA, to discuss PrimeC’s path forward in the short term.¹

The prospective, randomized, double-blind, placebo-controlled trial included 68 patients with ALS across Canada, Italy, and Israel. In the intent-to-treat (ITT) population, investigators recorded a 57% difference in complication-free survival favoring PrimeC over the 12-month treatment period. Results were even stronger in the pre-defined per protocol (PP) population, with differences of 73% (P = .02) favoring PrimeC during that time period.

"The latest results from the PARADIGM study are incredibly encouraging and provide compelling evidence of PrimeC's potential to significantly benefit people living with ALS. The substantial improvement in complication-free survival and the consistent slowing of disease progression highlight PrimeC's promise as an effective treatment," Jeremy M. Shefner, MD, PhD, professor of neurology at the Barrow Neurological Institute, said in a statement.¹ "Given that, for many clinicians and people with ALS, therapeutic options have recently been significantly limited; the urgency for effective new therapies is greater than ever. This development brings renewed hope to patients, and I am eagerly looking forward to seeing the program enter Phase 3 to advance the clinical development of this product."

PrimeC, an extended-release oral formulation comprised of ciprofloxacin and celecoxib, also resulted in slowed disease progression. As reported less than 2 weeks ago, treatment with the agent led to a 36% slowing of progression (P = .009) and 43% improved survival in comparison with placebo. The per-protocol analysis revealed even greater benefits, with a 40% (P = .003) improvement in ALS Functional Rating Scale-Revised (ALSFRS-R) scores and a 63% increase in survival rates, which the company noted was a “distinguished advancement in outcomes for a controlled 12-month ALS study."²

In the latest update, results showed a 13% difference in slow vital capacity (SVC) at 6 months and an even greater 20% difference favoring PrimeC at 12 months in the ITT population. Similarly, for the PP population, investigators recorded differences of 17% and 19% and the 6- and 12-month time points. In an analysis assessing rate of decline, defined as a drop of 4 points or less on ALSFRS-R, data showed that PrimeC outperformed placebo, with a ratio of 4.5 to 1 after 12 months of treatment.

Alon Ben-Noon

"We believe that these results are unprecedented in a 12-month ALS placebo-controlled clinical study. We are eager to present them to the FDA and other regulatory agencies to determine the path forward and to share the outcomes with potential partners currently conducting due diligence. As a management team, we are both confident and enthusiastic about the potential for PrimeC in the market," Alon Ben-Noon, chief executive officer at NeuroSense, said in a statement.¹

Among the 68-patient cohort who completed the 6-month double-blind portion of the trial, 96% opted to continue treatment with PrimeC through a 12-month open-label extension. The 6-month analysis, announced in December 2023, revealed a 29% difference in ALSFRS-R between PrimeC-treated participants and those on placebo. In the data readout, there was a noted 13% treatment difference favoring the agent on SVC, a measure of respiratory function.

PrimeC has also shown significant impacts on a subgroup of patients with high-risk ALS, defined as those with a higher risk of rapid disease progression by the European Network for the Cure of ALS. Between PrimeC- and placebo-treated patients, investigators recorded a 43% difference in ALSFRS-R, translating to a 5.04-point advantage for those on PrimeC (CI, 0.862-9.214; n = 38). In a subgroup of newly diagnosed patients who had symptoms for up to 12 months prior to baseline, treatment with the agent led to a 52% slowing of disease progression (P = .008) vs placebo in the PP population analysis.³

REFERENCES
1. NeuroSense’s PARADIGM ALS Clinical trial demonstrates up to 73% improved complication-free survival following statistically significant slowing of disease progression. News release. NeuroSense. July 9, 2024. Accessed July 11, 2024. https://www.prnewswire.com/news-releases/neurosenses-paradigm-als-clinical-trial-demonstrates-up-to-73-improved-complication-free-survival-following-statistically-significant-slowing-of-disease-progression-302191862.html
2. NeuroSense demonstrates statistically significant efficacy and survival benefits in people living with ALS: the promising results from the 12-month PARADIGM study highlight PrimeC’s potential as a disease modifying drug. News release. July 1, 2024. Accessed July 11, 2024. https://www.prnewswire.com/news-releases/neurosense-demonstrates-statistically-significant-efficacy-and-survival-benefits-in-people-living-with-als-the-promising-results-from-the-12-month-paradigm-study-highlight-primecs-potential-as-a-disease-modifying-drug-302186838.html
3. NeuroSense announces new positive data analysis from PARADIGM clinical trial demonstrating statistically significant slowing of disease progression in high-risk ALS patients. News release. NeuroSense. May 7, 2024. Accessed July 11, 2024. https://www.prnewswire.com/news-releases/neurosense-announces-new-positive-data-analysis-from-paradigm-clinical-trial-demonstrating-statistically-significant-slowing-of-disease-progression-in-high-risk-als-patients-302137999.html