NeuroSense says Phase 2b ALS trial hit primary TDP-43 endpoint

NeuroSense Therapeutics announced on June 29, 2026 that its Phase 2b PARADIGM study of PrimeC in amyotrophic lateral sclerosis met its primary efficacy endpoint, showing a statistically significant reduction in TDP-43 levels compared to placebo.¹ The company said this marks the first randomized, double-blind, placebo-controlled trial to show a treatment-linked drop in TDP-43 in ALS patients.¹

The measurement relied on a technique called the NeuroDex ExoSORT procedure, an immunoaffinity-based method that isolates neuron-derived extracellular vesicles, allowing detection of neuron-derived TDP-43 separate from TDP-43 shed by non-neuronal or peripheral tissue.¹ The company describes TDP-43 as the defining pathological hallmark of ALS, found in more than 97% of cases and considered a central driver of disease progression.¹

At the pre-specified Day 180 timepoint, PrimeC showed a statistically significant reduction in TDP-43 relative to placebo, with a p-value of 0.0421.¹ The company said the effect continued through the full study period, with treated patients showing lower TDP-43 than placebo at Day 540, reaching a p-value below 0.001.

NeuroSense also referenced earlier results from PARADIGM, including a slowing of ALSFRS-R decline of 36.5% at 12 months (p=0.008) and 32.8% at 18 months (p=0.007), along with a statistically significant survival benefit of about 15 months (HR 0.35, p=0.004) and a favorable safety profile with no new safety signals through 18 months.¹

The company said it has FDA clearance to begin its global Phase 3 PARAGON study and is preparing for the trial while continuing regulatory discussions in other jurisdictions, including Canada.¹ NeuroSense said the Phase 3 trial is expected to enroll approximately 300 participants, mostly in the United States.¹