First randomized, double-blind, placebo-controlled trial to demonstrate treatment-associated reduction of TDP-43 in people living with ALS
TDP-43 pathology is present in more than 97% of ALS cases and is widely recognized as a central driver of disease progression
PrimeC demonstrates target engagement with consistent effects across clinical outcomes, survival, and biomarkers, supporting its potential as a disease-modifying therapy
CAMBRIDGE, Mass., June 29, 2026 /PRNewswire/ -- NeuroSense Therapeutics Ltd. (NASDAQ: NRSN) ("NeuroSense"), a late-stage clinical biotechnology company focused on developing disease-modifying treatments for neurodegenerative diseases, today announced that its Phase 2b PARADIGM study of PrimeC in amyotrophic lateral sclerosis (ALS) has successfully met its primary efficacy endpoint, demonstrating a statistically significant reduction in TDP-43 levels compared to placebo. This is the first randomized, double-blind, placebo-controlled clinical study to demonstrate a treatment-associated reduction in TDP-43 in people living with ALS. The analysis was performed using the NeuroDex ExoSORT procedure, an immunoaffinity-based methodology that selectively isolates neuron-derived extracellular vesicles (NDEs). This approach enables measurement of neuron-derived TDP-43, providing a CNS-relevant signal that can be distinguished from TDP-43 released by non-neuronal cells and peripheral tissues.
TDP-43 is the defining pathological hallmark of ALS, present in more than 97% of cases, and is widely recognized as a central driver of disease progression. The observed reduction in TDP-43 provides biological evidence that PrimeC is engaging a core disease mechanism.
Primary Efficacy Endpoint Achieved with Statistical Significance
The randomized, double-blind, placebo-controlled Phase 2b PARADIGM study evaluated the safety, tolerability, biomarkers and efficacy of PrimeC in people with ALS. At Day 180, the pre-specified primary endpoint timepoint, PrimeC produced a statistically significant reduction in TDP-43 versus placebo (p=0.0421). The effect was sustained and deepened over the full 18 months of the study, with continuously treated PrimeC participants maintaining lower TDP-43 levels than the placebo arm at Day 540 (p<0.001).
These findings build upon previously reported clinical outcomes from the PARADIGM study, including:
Statistically significant slowing of ALSFRS-R decline at 12 and 18 months (36.5%, p=0.008; 32.8%, p=0.007)
Statistically significant ~15-month median survival benefit (HR 0.35, p=0.004)
Consistent modulation of TDP-43, iron-regulatory and ALS-associated microRNA, supporting multi-target engagement
Favorable safety and tolerability profile with no new safety signals observed over up to 18 months of treatment