NeuroSense – PrimeC

Background

PrimeC is a combination therapy composed of two FDA approved drugs: ciprofloxacin and celecoxib. PrimeC is reported to act by regulating several biological mechanisms associated with motor neuron degeneration in ALS such as inflammation and iron accumulation (ref: Neurosense website and alsnewstoday).

PrimeC has shown promising data in preclinical models of ALS. Data from Justin Ichida’s lab at University of Southern California (USC) showed that PrimeC was able to increase cell survival rate in patient derived neurons in a dish (ref: PR Newswire). Additionally, PrimeC treated zebrafish carrying ALS-causing gene mutations, showed improvement in their swimming abilities compared to their untreated peers (ref: Goldsthein et al., 2020).

NeuroSense launched two phase 1 and one phase 2aclinical trials at single centers in the US and Israel to test the safety and tolerability of PrimeC in humans. Data showed that PrimeC was safe and well tolerated after 12 months (Ref: Salomon-Zimri et al., 2023, ClinicalTrials.gov ID: NCT05232461 , NCT04090684 and NCT04165850)

Trial Design and Results

In 2022 NeuroSense started a Phase 2b, double-blind clinical trial (PARADIGM) in 69 subjects with ALS. The trial was randomized at a 2:1 ratio to receive PrimeC or placebo for 6 months followed by a 12-month open label extension period (Ref: ClinicalTrials.gov ID: NCT0535790):

The drug or placebo were administered orally twice a day. Subjects were evaluated every 2 months for safety, tolerability, and various efficacy measurements as secondary outcomes (Ref: ClinicalTrials.gov ID: NCT0535790).
This was a multicenter and international study that took place in Italy, Canada and Israel (Ref: ClinicalTrials.gov ID: NCT0535790).
In December 2023, NeuroSense published two press releases indicating that at the 6-month timepoint patients treated with PrimeC showed a slowing of disease that did not reach significance. More specifically, a 29% difference in ALS Functional Rating Scale (ALSFRS) and a 13% difference in the slow vital capacity (SVC, a measurement of respiratory function) was observed (Ref: Neurologylive). Further analysis of the per protocol population reported stronger improvement in the ALSFRS and SVC score (Ref: Neurologylive).
In July 2024, NeuroSense published a third press release stating that data from the Opel Label Extension (OLE) showed a decline in ALSFRS score and survival for people who had been taking PrimeC from the start of the trial compared to those who had started on placebo (ref: PR Newswire). Through 2024 NeuroSense met with different regulatory agencies and is now planning a larger phase 3 clinical trial to evaluate Prime C efficacy.

Summary

These clinical studies demonstrate safety and tolerability of PrimeC in people with ALS (Ref: Salomon-Zimri et al., 2023). The secondary functional measures potentially suggest clinical benefit; however, the trial was underpowered for efficacy measures so further trials are necessary for assessing PrimeC efficacy. It is important to note that no peer review data is available on the phase 2b trial and that the data reported here was only published in press releases. Until peer reviewed data is available, it will not be possible to draw any conclusion from the studies here described.

The Scientific Advisory Council, therefore, encourages NeuroSense to publish their results in a peer reviewed journal and looks forward to the results of the planned phase 3 clinical trial that should allow better understanding of Prime C efficacy.