Following positive phase 2a findings, NeuroSense’s agent PrimeC continued to show a mechanistic impact on biomarkers specific to patients with amyotrophic lateral sclerosis.
New stage 3 findings from a biomarker study showed levels of disease-related biomarkers remained unchanged in patients with amyotrophic lateral sclerosis (ALS) treated with standard of care, in contrast to the statistically significant decline in these biomarkers in those treated with NeuroSense's investigational agent PrimeC.1
The promising findings further confirm the mechanism of action of PrimeC, a novel extended-release oral formulation composed of a unique fixed-dose combination of ciprofloxacin and celecoxib, two FDA-approved drugs. More detailed results of the study are expected to be presented at the upcoming World Orphan Drug Congress, July 11-13, in Boston, Massachusetts. PrimeC is also currently being investigated in the phase 2b PARADIGM study (NCT05357950) that builds on positive findings from a recently concluded phase 2a study (NCT04165850).
"These results are very encouraging, especially in that they validate NeuroSense’s clinical strategy. The biomarker study, along with the data we collect from our phase 2b study, will inform the optimization of a pivotal phase 3 study of PrimeC in ALS," Alon Ben-Noon, chief executive officer, NeuroSense, said in a statement.1 "NeuroSense is honored to collaborate with the world-class [Massachusetts General Hospital] team on this critical study."
As mentioned, the data also build on positive findings from the phase 2a clinical study, in which PrimeC successfully met its safety and efficacy end points including reducing functional and respiratory deterioration and statistically significant changes in ALS-related biological markers. The study, which included 15 patients, showed trends of slowing disease progression on ALS Functional Rating Scale–Revised and on Functional Vital Capacity that were noted in the last 3 months of the 6-month study.2
Recently, NeuroSense announced enrollment for the first patient of PARADIGM. The double-blind, multicenter trial is expected to enroll 69 patients living with ALS and randomize them 2:1 to either PrimeC or placebo for a 6-month treatment period. Clinical trial end points include assessment of ALS-biomarkers, evaluation of clinical efficacy, and improvement in quality of life to demonstrate an attenuation in disease progression. Enrollment is expected to be completed by the end of 2022, with topline results being announced in Q2 2023.3
"NeuroSense remains at the forefront of biomarker research with the inclusion of a comprehensive portfolio of biomarkers in our Phase IIb study. This is essential in exploring mechanistic associations in ALS," Shiran Zimri, PhD, head, Scientific Programs, NeuroSense, said in a statement.1 "The use of neuronal derived exosomes, a cutting-edge technology, allows one to observe key alterations in biomarkers found in the central nervous system. We look forward to sharing more detailed results at the upcoming World Orphan Drug Congress."
The initial stage 1 of the biomarker study showed changes on ALS-related biomarkers such as TDP-43 accumulation and neuroinflammation among those treated with PrimeC. Additionally, investigators observed miRNA dysregulation, iron accumulation, lysosomal dysfunction, and impaired autophagy. In preclinical zebrafish models of ALS, the therapeutic was shown to improve motor performance, and recover the morphology of motor neurons, neuromuscular junction structures, and microglial cells.4