In a recent phase IIb PARADIGM trial, a novel treatment candidate for amyotrophic lateral sclerosis (ALS) called PrimeC has shown promising results. This formulation, which combines two FDA-approved drugs, ciprofloxacin and celecoxib, met its primary safety and secondary endpoints. The study results were presented by Merit Cudkowicz, MD, MSc, at the American Academy of Neurology annual meeting.
PrimeC is designed to target several key pathological mechanisms of ALS, including neuroinflammation, iron accumulation, and dysregulation of microRNA metabolism. Cudkowicz explained that ciprofloxacin and celecoxib work synergistically to address these factors. Ciprofloxacin, known for regulating microRNA and iron accumulation, is combined with celecoxib, which works on inflammation. This unique combination aims to provide a comprehensive approach to treating ALS.
The PARADIGM trial involved ALS patients who were treated with either PrimeC or a placebo for a period of 6 months. The study included both familial and sporadic ALS patients from Canada, Italy, and Israel. In total, 68 participants were included in the intention-to-treat analysis, with 62 participants in the per-protocol analysis. All participants had an upright slow vital capacity (SVC) of at least 60% at enrollment.
The primary endpoint of the study was safety and tolerability, and both the PrimeC and placebo groups showed good tolerability throughout the trial. The majority of participants completed the study on medication, indicating a favorable safety profile. Adverse events were reported as mild, transient, and expected. Additionally, the adjusted predicted SVC mean difference favored PrimeC, suggesting a potential benefit on respiratory function.
The study also evaluated the ALS Functional Rating Scale-Revised (ALSFRS-R) scores, which showed a trend favoring PrimeC at 6 months. In the per-protocol analysis, a statistically significant difference was observed, indicating a 37% slowing of disease progression with PrimeC. This promising outcome supports the advancement of PrimeC to a phase III pivotal trial.
Further analysis of biomarkers, including TDP-43 and prostaglandin 2, may provide additional insights into the clinical results of PrimeC. The positive outcomes observed in ALS patients have paved the way for studying PrimeC in other neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. NeuroSense Therapeutics, the drug developer, has already initiated enrollment in a phase II Alzheimer’s study using PrimeC.
Overall, the results of the PARADIGM trial demonstrate the potential of PrimeC as a novel treatment approach for ALS. The combination of ciprofloxacin and celecoxib has shown favorable safety outcomes and promising effects on disease progression in ALS patients. With further research and clinical trials, PrimeC could offer new hope for individuals battling ALS and other neurodegenerative disorders.
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