JAMA Neurology Publishes PrimeC Phase 2b ALS Data as NeuroSense Advances Toward Phase 3
JAMA Neurology published Phase 2b PARADIGM results for PrimeC in ALS, showing slower functional decline, fewer ALS-related complications and longer survival. NeuroSense is preparing a Phase 3 trial and received Brazilian patent protection through October 2042.
Results from the PARADIGM Phase 2b trial evaluating PrimeC in people living with amyotrophic lateral sclerosis (ALS) have been published in JAMA Neurology. The randomized, double-blind, placebo-controlled trial evaluated the safety, biological activity, and potential clinical effects of PrimeC during a 6-month blinded treatment period followed by a 12-month open-label extension.
PrimeC demonstrated a safety profile comparable to placebo over 18 months, with most treatment-related adverse events mild to moderate and transient. Continuous treatment with PrimeC was associated with slower functional decline and improved long-term outcomes, including a 7.92-point advantage in ALSFRS-R at 18 months, which represents over 36% benefit of slowing disease progression (p=0.007) and significant improvement in bulbar function (P=0.001).
Early initiation of PrimeC was associated with a 64% relative reduction in risk of ALS-related complications (p=0.02), including respiratory failure, hospitalization, or death. PrimeC treatment was also associated with significant modulation of ALS-related microRNAs and iron-regulatory biomarkers, supporting its biological activity.
In the PARADIGM study (NCT05357950), patients treated with PrimeC saw an estimated median overall survival of 36.3 months, compared to 21.4 months for patients initially assigned to placebo who later crossed over to active treatment in the open-label extension. A log-rank test comparing survival curves demonstrated statistical significance, and a Cox proportional hazards model showed that PrimeC treatment was associated with a 65% reduction in the risk of death compared to placebo.
The randomised, double-blind trial enrolled 68 patients to receive either PrimeC or placebo for six months, after which all patients received the study drug during the open-label extension. NeuroSense previously reported positive top-line results from the trial, including statistically significant slowing of disease progression and favourable safety and tolerability, with a 29% difference in ALSFRS-R and 13% difference in Slow Vital Capacity in results announced in December 2023.
These findings support the continued clinical development of PrimeC and its advancement to a confirmatory Phase 3 clinical trial in ALS. The company said it is preparing for initiation of a Phase 3 pivotal clinical trial for PrimeC in ALS (PARAGON), following positive Phase 2b PARADIGM results and clearance from the FDA.
PrimeC is a proprietary fixed-dose oral therapy combining ciprofloxacin and celecoxib in a synchronized, extended-release formulation. The Brazilian Patent and Trademark Office has granted Brazilian Patent No. BR 112024007727-6, entitled "Compositions Comprising Ciprofloxacin and Celecoxib," providing protection for PrimeC in Brazil and extending patent coverage through October 2042, following prior approval of the corresponding U.S. patent (12,097,185) and Australian patent (2022370513).