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DENVER -- A novel treatment candidate for amyotrophic lateral sclerosis (ALS) met its primary safety and secondary endpoints in the phase IIb PARADIGM trial.

ALS patients treated with PrimeC -- a formulation of two FDA-approved drugs, ciprofloxacin and celecoxib -- had similar safety outcomes as those treated with placebo, reported Merit Cudkowicz, MD, MSc, of Massachusetts General Hospital in Boston, in a late-breaking session at the American Academy of Neurology annual meeting.

Moreover, scores on the ALS Functional Rating Scale-Revised () appeared to favor PrimeC at 6 months. In an intention-to-treat analysis, the between-group difference in adjusted ALSFRS-R scores was not significant (2.23 points, P=0.12). But in a per-protocol analysis at 6 months, a difference of 37.4% favoring PrimeC was statistically significant (3.22 points, P=0.03).

PrimeC is designed to synergistically target several key pathological mechanisms of ALS, including neuroinflammation, iron accumulation, and dysregulation of microRNA metabolism, Cudkowicz noted. A small showed that the treatment had a favorable safety profile and suggested it might slow functional and respiratory decline in ALS.

"Ciprofloxacin -- and actually, all antibiotics in this class -- has been shown to regulate microRNA and also works on iron accumulation," Cudkowicz said in an interview with 名媛直播. "Celecoxib works on inflammation." When in an earlier ALS study, celecoxib did not show benefits.

randomized patients with familial or sporadic ALS to PrimeC (45 people) or placebo (23 people) in Canada, Italy, and Israel for 6 months. The intention-to-treat analysis was based on 68 people and the per-protocol analysis was based on 62. All participants had an upright slow vital capacity (SVC) of at least 60% at enrollment.

In both the PrimeC and placebo groups, 60% of participants were men. Mean age in the PrimeC group was 59 years; in the placebo arm, it was 55. About 90% of participants were on riluzole (Rilutek).

The primary endpoint was safety and tolerability, defined as the time to discontinuation or completion of the assigned treatment in the double-blind period. "Tolerability was quite good, with the majority of participants both in the active and in the placebo group completing the trial on medication," Cudkowicz said.

All adverse events were mild, transient, and expected, she pointed out. Over 6 months, the adjusted predicted SVC mean difference was 17.2% (P=0.39) in the per-protocol dataset and 13.3% (P=0.5) in the intention-to-treat dataset, favoring PrimeC. Trends in neurofilament light (NfL) suggested a small decrease over 6 months with PrimeC.

These findings indicate that PrimeC is safe and may have a positive effect on ALS clinical outcomes, Cudkowicz stated. "We did see a specific significant slowing of disease progression of 37% in the per-protocol population," she pointed out.

The data supported moving forward to a phase III pivotal trial, Cudkowicz added. Further analysis of biomarkers, including efficacy biomarkers TDP-43 and prostaglandin 2, may help shed light on the clinical results, she said.

PrimeC is also being studied in according to drug developer NeuroSense Therapeutics. Enrollment in the phase II Alzheimer's study is underway.

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