NeuroSense Therapeutics has announced transformative findings from its PARADIGM clinical trial of PrimeC, revealing a significant impact on the regulation of microRNAs (miRNAs) in patients with Amyotrophic Lateral Sclerosis (ALS). The trial provides compelling evidence of the drug's potential to alter the underlying mechanisms of the disease, which has long been considered untreatable at its core.
ALS is a fatal disease characterized by the relentless destruction of motor neurons, leading to loss of muscle function, speech, and eventually, the ability to breathe. Understanding the molecular drivers of ALS is key to finding a way to slow or stop its progression. The PARADIGM trial results represent a breakthrough in that understanding.
Key Findings from the PARADIGM Trial
The PARADIGM trial revealed that PrimeC regulates specific miRNAs, which are key genetic markers that control gene expression involved in ALS progression. These miRNAs were unchanged in the placebo group, underscoring the profound impact of PrimeC on ALS's pathological pathways. MicroRNAs play a crucial role in regulating how genes express themselves, and their dysregulation has long been linked to ALS. By restoring balance to these genetic regulators, PrimeC offers a new method of combating this devastating disease.
PrimeC enhances microRNA (miRNA) maturation, addressing the underlying mechanisms of ALS. By influencing Dicer, the endonuclease that processes precursor miRNA into active forms, PrimeC may restore the balance of dysregulated miRNAs in ALS patients. This modulation is thought to facilitate the production of functional miRNAs that regulate gene expression, allowing PrimeC to target disrupted genetic pathways in ALS and potentially slow disease progression and improve patient outcomes. Patients treated with PrimeC demonstrated consistent effect in miRNA manifestation, with no similar changes seen in the placebo group. This clear distinction offers compelling evidence of PrimeC's potential as a disease modifying treatment, rather than a symptomatic one.
Clinical Trial Details
PARADIGM is a prospective, multinational, randomized, double-blind, placebo-controlled Phase 2b clinical trial of PrimeC in ALS. The trial included 68 participants living with ALS in Canada, Italy, and Israel. 96% of the trial participants who completed the 6-month double-blind portion of the trial chose to receive treatment with PrimeC through a 12-month open label extension. Furthermore, to date (June 2024) all participants that completed the 18-month trial treatment duration, requested to continue PrimeC, which is provided to them in an Investigator Initiated Trial, not limited with time.
In the 6-month double-blind segment of the trial, the data showed clinically meaningful signs of efficacy with a 29% difference in favor of PrimeC vs placebo in analysis of the intent to treat (ITT) population. In the PP top-line analysis from PARADIGM, a statistically significant slowing of disease progression was observed with a 37.4% (p=0.03) difference in ALSFRS-R in favor of PrimeC vs placebo. Most patients enrolled in both the active and placebo arms of the trial were concurrently treated with Riluzole, the ALS standard of care medication, indicating PrimeC slowed disease progression well beyond the level afforded by the FDA approved ALS drug.
About PrimeC
PrimeC, NeuroSense's lead drug candidate, is a novel extended-release oral formulation composed of a unique fixed-dose combination of two FDA-approved drugs: ciprofloxacin and celecoxib. PrimeC is designed to synergistically target several key mechanisms of ALS that contribute to motor neuron degeneration, inflammation, iron accumulation and impaired ribonucleic acid ("RNA") regulation to potentially inhibit the progression of ALS. NeuroSense completed a Phase 2a clinical trial which met its safety and efficacy endpoints including reducing functional and respiratory deterioration and statistically significant changes in ALS-related biological markers indicating PrimeC's biological activity. PrimeC was granted Orphan Drug Designation by the U.S. Food and Drug Administration and the European Medicines Agency.
Professor Noam Shomron, a world-leading scientist in the field of genetics, collaborated on this work.
In conclusion, PrimeC demonstrated beneficial regulation of key miRNAs, supporting its potential to engage critical genetic targets involved in ALS progression. The 2-fold reduction of several miRNAs following PrimeC treatment is particularly striking, offering both a powerful biomarker for tracking ALS and a potential pathway for new therapeutic strategies. This regulation of miRNAs underscores PrimeC's capability to influence ALS at the regulatory level, where previous treatments have struggled.
