お知らせ • Aug 02
NeuroSense Therapeutics Ltd. Announces Positive Biomarker Data from ALS Phase 2B Clinical Trial
NeuroSense Therapeutics Ltd. announced positive 12-month iron biomarker data from its Phase IIb study (PARADIGM), which evaluated the safety and efficacy of PrimeC in people living with Amyotrophic Lateral Sclerosis (ALS). This data provides additional insights that align with the Company's recent announcements of improved survival by 43% and slowed disease progression by 36%. ALS is a multifactorial disease in which iron and its related proteins play a critical role in its pathophysiology. These new results demonstrate the target engagement of PrimeC in iron regulation, which is linked to disease mitigation and improved survival. Iron metabolism is crucial in ALS pathology, with transferrin and ferritin being significant contributors to the progress of the disease. Iron accumulation in various brain regions of ALS patients has been linked to neuronal damage. Elevated ferritin levels, an indicator of iron storage, are consistently observed in ALS patients and are associated with reduced survival and potential oxidative stress. Conversely, lower levels of transferrin, the primary iron transport protein, contribute to iron dysregulation and disease progression. The 12-month study results show a significant decrease in ferritin levels and a corresponding increase in transferrin levels, both indicating alleviation of the pathology. Iron levels remained stable over the 12-month dosing period, with a mean difference of 4.536 µmol/L (95% CI [1.143, 7.929], p=0.01) compared to those who started on placebo and transitioned to PrimeC after the initial 6-month double-blind phase. These positive changes in iron metabolism align with improved clinical outcomes. Patients on PrimeC maintained better functionality and survival rates compared to those on placebo. The Company is currently compiling additional data to share with the FDA for discussion to determine the clinical and regulatory path forward. Additionally, the Company is continuing advanced discussions with several potential development partners to explore marketing opportunities following the potential completion and approval of PrimeC for ALS. Amyotrophic lateral sclerosis ("ALS") is an incurable neurodegenerative disease that causes complete paralysis and death within 2-5 years from diagnosis. Every year, more than 5,000 people are diagnosed with ALS in the U.S. alone, with an annual disease burden of $1 billion. The number of people living with ALS is expected to grow by 24% by 2040 in the U.S. and EU. Disease progression is measured by the ALS Functional Rating Scale-Revised (ALSFRS-R), which is the most widely used ALS tracking tool accepted by the FDA, utilized by neurologists treating ALS patients, in clinical trials, and by other regulators to determine disease progression. It tracks 12 changes in a person's physical abilities over time including functions such as: speech, walking, climbing stairs, dressing/hygiene, handwriting, turning in bed, cutting food, salivation, swallowing, and breathing. A single point change on the ALSFRS-R has a significant impact on ALS patients, such as the transition from independent feeding to requiring assistance or independent breathing to needing to use a machine ventilator. PARADIGM is a prospective, multinational, randomized, double-blind, placebo-controlled Phase 2b (NCT05357950) 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. As previously reported, 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. 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.