Announcement • Mar 17
Neurosense Therapeutics Ltd. Publishes Paradigm Phase 2B Trial Results of PrimeC in ALS
NeuroSense Therapeutics Ltd. announced that results from the Phase 2b clinical trial (PARADIGM) evaluating PrimeC in people living with amyotrophic lateral sclerosis (ALS) have been published in JAMA Neurology. PARADIGM was a randomized, double-blind, placebo-controlled trial that 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 is a novel fixed-dose oral combination formulated in a synchronized extended-release composition designed to concurrently address three key mechanisms implicated in ALS progression: neuroinflammation, iron dysregulation, and microRNA-mediated regulatory pathways. Key highlights from the PARADIGM phase 2b study published include: 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 associated with significant modulation of ALS-related microRNAs and iron-regulatory biomarkers, supporting its biological activity and reinforcing the potential for disease-modifying effects. These findings support the continued clinical development of PrimeC and its advancement to a confirmatory Phase 3 clinical trial in ALS. PARADIGM was a multinational Phase 2b randomized, double-blind, placebo-controlled clinical trial conducted at ALS referral centers in Italy, Canada, and Israel. The study enrolled 68 participants with definite or probable ALS, randomized in a 2:1 ratio to receive PrimeC or placebo for six months. The double-blind phase was followed by a 12-month open-label extension, during which all participants received PrimeC while maintaining blinding to original treatment assignment. Even though the trial was not powered to demonstrate definitive efficacy, participants who received PrimeC from the outset maintained a clinically meaningful 7.92-point functional advantage in ALSFRS-R at 18 months, which represents over 36% benefit of slowing disease progression (p=0.007), with the largest improvement observed in the bulbar domain (p=0.001), a key determinant of speech, swallowing, and quality of life in ALS. In addition, ALS complication-free survival demonstrated a 64% relative risk reduction favoring early treatment (p=0.02), suggesting potential long-term clinical benefit. The trial also demonstrated biological activity consistent with PrimeC's proposed multi-pathway mechanism. Markers of iron metabolism, which are frequently dysregulated in ALS, showed favorable significant changes, including preservation of transferrin levels and stabilization of ferritin. In parallel, plasma microRNA analysis revealed statistically significant downregulation of ALS-associated microRNAs miR-199a-3p, miR-199a-5p, miR-181a-5p, and miR-181b-5p, which have been linked to disease severity and prognosis. Together, these findings provide biological evidence that PrimeC engages disease-relevant pathways and support its continued development as a potential disease-modifying therapy. PrimeC is an investigational fixed-dose oral combination therapy composed of celecoxib and ciprofloxacin in a synchronized extended-release formulation. The therapy is designed to simultaneously target multiple biological mechanisms implicated in ALS progression, including neuroinflammation, iron dysregulation, and microRNA dysregulation. The therapeutic rationale for PrimeC is supported by preclinical evidence across ALS disease models and human induced pluripotent stem cell–derived motor neuron systems and has now been evaluated in a randomized Phase 2b clinical trial.
