ALS Candidate PrimeC Shows Greater Treatment Effect in High-Risk ALS
Subgroup analyses support PrimeC’s potential in ALS treatment, aiming to inform upcoming trials for efficacy.
Jeremy M. Shefner, MD, PhD
Newly announced analyses from the phase 2b PARADIGM trial (NCT05357950) showed that treatment with PrimeC (NeuroSense), an investigational agent made up of ciprofloxacin and celecoxib, resulted in statistically significant slowing of disease progression in individuals with high-risk amyotrophic lateral sclerosis (ALS) after 6 months of treatment. NeuroSense plans to utilize the new subgroup findings to help inform the design of its upcoming trial and increase the probability of success and cost-effectiveness.1
In this multinational, randomized, double-blind, placebo-controlled trial, 68 patients with ALS were included to assess efficacy and safety of PrimeC. At 6 months, high-risk patients in the pre-specified per protocol (PP) population, defined by the European Network for the Cure of ALS (ENCALS) Risk Factor as those with a higher risk for rapid disease progression, demonstrated a 43% difference compared with placebo on ALS Functional Rating Scale-Revised (ALSFRS-R), the primary end point. Overall, this translated to a 5.04-point difference in favor of PrimeC (CI, 0.862-9.214; n = 38).
In comparison, previously reported, top-line data from the 6-month double-blind segment of the trial showed clinically meaningful signs of efficacy with a 29% difference in ALSFRS-R (P = .13) and a 13% difference in slow vital capacity (SVC)(P = .5), both in favor of PrimeC in the intent-to-treat (ITT) population. In the ITT population, new data on high-risk patients with ALS showed that treatment with PrimeC resulted in a 31% (P = .13) reduction in disease progression, translating to a 3.2-point difference in the ALSFRS-R in favor of PrimeC (CI, –1.03 to 7.43; n = 41).
"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, professor of neurology at the Barrow Neurological Institute, and an advisory to NeuroSense, said in a statement.1 "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."
The study also evaluated the effect of PrimeC in a subgroup of newly diagnosed patients who had symptoms for up to 12 months prior to the baseline visit. In these participants, treatment with the agent resulted in a 52% slowing of disease progression (P = .008) vs placebo in the PP population analysis. This translated to a 7.76-point difference in the ALSFRS-R in favor of PrimeC (CI, 2.27-13.25; n = 22). In the ITT population, newly diagnosed participants treated with active therapy experienced a 36% reduction (P = .14) in disease progression, which translated to a 4.56-point difference in the ALSFRS-R in favor of PrimeC (CI, –1.6 to 10.72; n = 25).
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In total, 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. In the PP analysis, participants with a disease duration of up to 18 months had a 38% change in ALSFRS-R with PrimeC (P = .054). This group continued to maintain this type of disease slowing, with a 37% reduction in symptom scores at 24 months (P = .047).
"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," Alon Ben-Noon, chief executive officer at NeuroSense, said in a statement.1 "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."
When NeuroSense announced the 6-month, top-line findings in January 2024, the company also confirmed its CMC development plans for a phase 3 trial with the intention of subsequent marketing approval. During that time, the company noted that it would anticipate End of Phase 2 meetings with the FDA and the European Medicines Agency in Q2 of this year. Thus far, the agent has been granted orphan drug designation by both agencies.
At the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado, Merit Cudkowicz, MD, MSc, an ALS expert, sat down to discuss the primary drugs used in PrimeC, and why they were chosen for ALS treatment. In the video below, Cudkowicz, chair of neurology at Massachusetts General Hospital, discussed the key safety, clinical, and biomarker findings from the phase 2 study, as well as expectations for the upcoming phase 3 trial.
