PARADIGM, an ongoing phase 2 placebo-controlled trial, will have additional biomarker data released in the first half of 2024.
Shortly after positive topline data from the phase 2 PARADIGM study (NCT05357950) of PrimeC was released, NeuroSense Therapeutics has announced that the FDA has confirmed its CMC development plans for a phase 3 pivotal trial with the intention of subsequent marketing approval. In collaboration with Biogen, the company also plans on releasing data from PARADIGM assessing PrimeC in biomarkers relevant to the pathology of amyotrophic lateral sclerosis (ALS).1
PrimeC, a unique fixed-dose combination of ciprofloxacin and celecoxib, is designed to synergistically target several key mechanisms of ALS that contribute to motor neuron degeneration, inflammation, iron accumulation, and impaired ribonucleic acid (RNA) regulation. The agent met its primary end point in PARADIGM, demonstrating a 37.4% (P = .03) difference on ALS Functional Rating Scale Revised (ALSFRS-R) at 6 months vs placebo, while maintaining a strong safety profile. Additionally, investigators recorded a 13% treatment difference in slow vital capacity favoring PrimeC.
"These data provide an exciting justification and indication for a pivotal Phase 3 trial," Jeffrey Rosenfeld, MD, PhD, professor of neurology at Loma Linda University and a member of NeuroSense’s scientific advisory board, said in a statement.1 "The complexity of ALS pathology warrants a multi-drug therapeutic strategy and it is especially gratifying to see this combination therapy advance. The pending data on biomarkers of neurodegeneration will also be of great interest, as we continue to better understand the benefits of PrimeC and promote this approach."
In its announcement, NeuroSense noted that it anticipates End of Phase 2 meetings with the FDA and the European Medicines Agency in Q2 of this year. In addition to demonstrating efficacy in the 6-month PARADIGM findings, an independent study comparing PrimeC’s effect against 2 previously approved ALS agents showed that PrimeC had the largest impact on improving motor neuron survival. Thus far, the agent has been granted orphan drug designation by the FDA and European Medicines Agency.
In addition to ALS, NeuroSense is testing the efficacy and safety of PrimeC in patients with mild to moderate Alzheimer disease (AD). Otherwise known as the RoAD study (NCT06185543), the recently enrolled phase 2 trial will include 20 individuals who will be randomly assigned 1:1 to either study drug or placebo for a 52-week period. Participants will be allowed to receive standard of care treatment of approved products or their combination (rivastigmine, donepezil, galantamine, memantine, aducanumab, and lecanemab). Following completion of 12 months of treatment, data lock will be performed, and data will be analyzed.2
In early 2023, the company reported positive final results from a biomarker study assessing the combination therapy as a treatment for AD. Preliminary results from the study, showed that TDP-43, a novel biomarker, was elevated in patients with AD compared with healthy controls. NeuroSense believes that these results demonstrate the importance of TDP-43 pathology in AD and suggest the potential efficacy of the platform technology in this disease population.3
“The clinical efficacy seen in the topline PARADIGM trial results demonstrate PrimeC's potential to render a significant and meaningful clinical benefit to people living with ALS, as any slowing of progression of this incurable disease is meaningful from both a clinical and patient perspective," Alon Ben-Noon, chief executive officer of NeuroSense, said in a statement.1 "This is perhaps one of the most significant outcomes seen to date. We believe that these data in conjunction with hopefully correlative neurofilament readouts this month could lead to a strategic partnership and an expedited regulatory pathway for PrimeC towards the market."
A previously completed phase 2a study (NCT04165850) first demonstrated the positive safety of PrimeC in individuals with ALS. Comprised of 15 patients with the disease, findings showed no serious adverse events related to the study drug. Four patients experienced AEs related to the study drug; however, none were unexpected and most were mild or moderate (69%). When compared with the PRO-ACT cohort a mean difference of 0.18 points/month in ALSFRS-R progression rate (ns, 95% CI, –0.23 to 0.59) and 0.90 points/month in percentage predicted FVC (ns, 95% CI, –0.52 to 2.32) was observed, representing a difference of 18% and 30%, respectively.4