PrimeC in ALS patients shown to extend complication-free survival

NeuroSense treatment also improves quality of life, new trial data show

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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Treatment with NeuroSense Therapeutics’ PrimeC was found to extend patients’ time without complications or death, and to lead to clinically meaningful effects on quality of life, among those with amyotrophic lateral sclerosis (ALS).

The new data comes from the PARADIGM Phase 2b study (NCT05357950), a fully enrolled clinical trial that’s testing oral PrimeC against a placebo in 68 adults with ALS. Participants had experienced their first symptoms within the prior 30 months and could continue to receive their standard ALS medications.

These findings come shortly after positive top-line data from the PARADIGM trial that was announced late last year. In that report, the therapy was seen to be safe and well tolerated by patients — and to significantly slow disease progression in the group of participants who complied with the trial’s protocol.

“PrimeC’s demonstrated positive effect on quality of life and survival, aligned with the already positive clinical outcome measures, in a relatively small Phase 2b clinical trial truly demonstrates its potential to deliver a meaningful benefit,” Ferenc Tracik, MD, NeuroSense‘s chief medical officer, said in a company press release.

“From a clinical perspective,” Tracik said, speaking of the therapy’s performance in the trial, “these parameters are crucial to neurologists, but more importantly to people living with ALS.”

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PrimeC is a fixed-dose combination of ciprofloxacin, an antibiotic used to treat bacterial infections, and celecoxib, an anti-inflammatory agent. Both therapies are approved in the U.S. and have well-established safety profiles; together, they are expected to slow ALS progression by key mechanisms thought to drive nerve cell degeneration.

The PARADIGM trial is testing a long-acting formulation of PrimeC, given at a total daily dose of 1,496 mg, in 68 ALS patients, ages 18 to 75. The participants were randomly assigned to receive either PrimeC (45 patients) or a placebo (23 patients), taken as two tablets twice daily for six months, on top of their standard ALS treatments.

The study’s primary goals are to assess the treatment’s safety and tolerability, and whether it can reduce the levels of certain ALS blood biomarkers. Secondary measures — the focus of this data — include changes in the rate of disease progression, assessed with the ALS Functional Rating Scale-Revised (ALSFRS-R), as well as changes in lung function, quality of life, and survival.

NeuroSense in December reported that the therapy was generally safe and well tolerated — and that 96% of patients were joining an open-label extension in which they would continue to receive PrimeC after the initial six months. In the open-label part, both participants and researchers know the exact medication being given.

In the overall patient population, participants given PrimeC had a 29% slower disease progression and a 13% slower lung function decline than those on the placebo, but the differences failed to reach statistical significance. However, an analysis of the trial’s per-protocol population, covering 62 participants who complied with the trial’s established protocol or rules, showed a significant slowing of disease progression compared with a placebo, by 37.4%.

The company now reported that PrimeC also exerted positive effects in other clinical outcomes, including in the physical and mental aspects of quality of life. The therapy also extended complication-free survival compared with a placebo.

The positive impact of PrimeC on quality of life and complication-free survival, together with its demonstrated ability to meaningfully slow down disease progression, is of great value, as we see that we have the potential to profoundly affect patients’ lives across the board.

Complications were defined as respiratory failure — the need for a breathing tube or noninvasive ventilation for more than 22 hours per day over at least 10 consecutive days — hospitalization due to ALS complications, or advances in ALS disease stages. Complication-free survival, a measure of the time to death from any cause or any of those complications, was reduced with PrimeC by 53%.

“The positive impact of PrimeC on quality of life and complication-free survival, together with its demonstrated ability to meaningfully slow down disease progression, is of great value, as we see that we have the potential to profoundly affect patients’ lives across the board,” said Alon Ben-Noon, NeuroSense’s CEO.

The company now is examining how PrimeC impacts the levels of neurofilaments, biomarkers of nerve cell damage, as well as the ALS blood biomarkers TDP-43 and prostaglandin J2. The neurofilament analysis is being done in collaboration with Biogen and is expected until the end of March. Meanwhile, TDP-43 and prostaglandin analyses are expected in the first half of the year.

“We are in great anticipation to soon report on the status of our collaboration on neurofilaments and how this may contribute to expediting the development of PrimeC,” Ben-Noon said.