Key Takeaways:
NeuroSense Therapeutics Ltd. said its Phase 2b PARADIGM study of PrimeC in amyotrophic lateral sclerosis met its primary endpoint, showing a statistically significant reduction in TDP-43 protein levels compared with placebo at Day 180 (p=0.0421).
"Achieving the primary endpoint of PARADIGM with a statistically significant reduction in TDP-43 marks a defining moment for NeuroSense and for ALS research," Alon Ben-Noon, chief executive officer of NeuroSense, said. "Combined with the clinically meaningful slowing of disease progression, significant survival benefit, and consistent biomarker findings previously reported from PARADIGM, these results provide a compelling and highly differentiated body of evidence supporting PrimeC's potential as a disease-modifying therapy."
TDP-43 pathology is present in more than 97 percent of ALS cases and is recognized as a central driver of disease progression. The analysis used NeuroDex's ExoSORT procedure, an immunoaffinity-based method that isolates neuron-derived extracellular vesicles from blood samples, enabling measurement of CNS-relevant TDP-43 distinct from peripheral sources. The effect deepened over the full 18-month study, with continuously treated PrimeC participants maintaining lower TDP-43 levels than the placebo arm at Day 540 (p<0.001).
The biomarker findings build on previously reported clinical outcomes from the same study. PrimeC slowed ALSFRS-R decline by 36.5 percent at 12 months (p=0.008) and 32.8 percent at 18 months (p=0.007). The treatment also produced a median survival benefit of approximately 15 months (HR 0.35, p=0.004). PrimeC, an extended-release oral formulation combining ciprofloxacin and celecoxib, showed a favorable safety profile with no new signals over up to 18 months of treatment.
"One of the central questions in ALS drug development is whether a therapy is truly affecting the underlying biology of the disease," Prof. Merit Cudkowicz, director of the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital and professor of neurology at Harvard Medical School, said. "The TDP-43 findings reported in PARADIGM are particularly important because they suggest target engagement of a pathological process present in the majority of people with ALS."
NeuroSense has secured FDA clearance to initiate its global Phase 3 PARAGON study, which is expected to enroll approximately 300 participants primarily in the United States. The company is also advancing regulatory interactions across multiple jurisdictions, including Canada.
The TDP-43 reduction provides biological evidence that PrimeC is engaging a core disease mechanism in ALS, a condition that causes complete paralysis and death within two to five years of diagnosis. More than 5,000 people are diagnosed with ALS annually in the US alone, with an annual disease burden of $1 billion. The number of people living with ALS is expected to grow 24 percent by 2040 in the US and EU.
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