PrimeC significantly slows ALS progression in certain trial patients

Benefits seen for those newly diagnosed or at high risk of progression

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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PrimeC, a treatment candidate for amyotrophic lateral sclerosis (ALS), was found to significantly slow disease progression in certain subgroups of patients in the ongoing PARADIGM Phase 2b trial, according to new data announced by its developer NeuroSense Therapeutics.

Benefitting most were people at high risk of rapid disease progression and those newly diagnosed with the neurodegenerative disease. Specifically, patients at high risk experienced a 43% slower rate of progression after six months when given PrimeC compared with a placebo, while those newly diagnosed had a 52% slower rate.

These findings come from the trial’s per protocol population, an analysis that covered the 62 participants in PARADIGM — of a total 68 — who adhered well to the trial’s established protocol, meaning its rules. Previous data from the Phase 2b trial (NCT05357950) had already shown that PrimeC significantly slowed disease progression in this group; this data expands on that.

NeuroSense now is planning the launch of a Phase 3 trial later this year to continue to study PrimeC in ALS patients. Findings from that trial may potentially support applications to regulatory agencies requesting the drug’s approval, according to the company.

“The impressive results of these new analyses raise further enthusiasm for the potential impact of PrimeC on people with ALS,” Jeremy M. Shefner MD, PhD, a professor of neurology at the Barrow Neurological Institute, in Arizona, and a NeuroSense advisor, said in a company press release.

“With the magnitude of its effect and consistency across subgroups, PrimeC, if approved following a Phase 3 trial, could significantly improve the standard of care for people with ALS,” Shefner said.

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Phase 2b PARADIGM trial testing PrimeC in 68 ALS patients

PrimeC is an oral fixed-dose combination of two medications approved in the U.S.: ciprofloxacin, an antibiotic used to treat bacterial infections, and celecoxib, an anti-inflammatory agent.

The combination therapy is believed to slow ALS progression by interfering with key mechanisms involved in nerve cell degeneration. Among these mechanisms are inflammation, iron accumulation, and RNA processing.

The ongoing PARADIGM trial is testing a long-acting formulation of PrimeC in 68 adults with ALS, ages 18 to 75, whose first symptoms began a maximum of 2.5 years prior to enrollment. The participants were randomly assigned to receive PrimeC or a placebo, taken as two tablets twice daily for six months, while continuing with their standard ALS treatments.

The majority (96%) then chose to join an open-label extension in which all are receiving PrimeC for up to one year.

Six-month data from all patients, regardless of whether or not they adhered to the study protocol or completed treatment as intended — called the intention-to-treat (ITT) population — showed a meaningful trend toward slower disease progression with PrimeC, by 29% compared with placebo use. This difference, however, failed to reach significance in this group.

Importantly, an analysis of the trial’s per-protocol population did show a clinically significant slowing of disease progression compared with the placebo, by 37.4%. The therapy also extended by 53% the amount of time patients lived without a complication, such as needing ventilation, being hospitalized due to ALS, or advancing in their ALS disease stage.

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Developer says these results will inform design of Phase 3 trial

The new analysis now focused on certain subgroups of patients in the per-protocol population. One was a group of 38 individuals with high-risk ALS — those deemed at high risk of rapid disease progression based on European Network for the Cure of ALS (ENCALS) scores. A second group comprised 22 patients who had experienced their first symptoms a maximum of one year before enrollment; these patients were characterized as newly diagnosed.

PrimeC slowed disease progression in these two groups, as shown by a significant 5.04- and 7.76-point difference compared with the placebo in ALS Functional Rating Scale-Revised (ALSFRS-R) scores.

Participants in the per-protocol population with longer disease duration also experienced a slowing in ALS progression, data showed.

We believe this is one of the most compelling results seen to-date in an advanced, double-blind clinical trial in ALS, demonstrating slowing the progression of ALS in patients in earlier stages with an aggressive disease.

While high-risk and newly diagnosed ALS patients in the ITT population also experienced a trend toward slower progression with PrimeC, the findings again failed to reach statistical significance in this population.

These subgroup analyses will help inform the design of the upcoming pivotal trial, the company said.

“We believe this is one of the most compelling results seen to-date in an advanced, double-blind clinical trial in ALS, demonstrating slowing the progression of ALS in patients in earlier stages with an aggressive disease,” said Alon Ben-Noon, NeuroSense’s CEO.

“Seeing PrimeC’s significant impact in the general PARADIGM population in all various clinical aspects, and even more in multiple sub-groups on the gold-standard ALSFRS-R, is truly gratifying, and we are looking forward to analyzing and reporting on the 12-month study survival data in the next few weeks,” Ben-Noon added.