NeuroSense PrimeC PK Data in ALS could Trigger US Enrollment

A new formulation of NeuroSense’s amyotrophic lateral sclerosis therapeutic PrimeC could pave the way for an expansion of its ongoing Phase IIb PARADIGM study into the United States.

The pharmacokinetic profile of a new extended-release formulation of PrimeC showed a simultaneous release of ciprofloxacin and celecoxib, the two drug components that combine to form the NeuroSense treatment. The PK study, comprised of 20 participants, compared PrimeC to the reference products. Patients received either two PrimeC tablets or co-administered ciprofloxacin and celecoxib every 12 hours for 6.5 days.

The data, released Wednesday, showed PrimeC generated a simultaneous release of ciprofloxacin and celecoxib compared to the co-administration of the reference drugs. The drug concentrations consistently remained within the therapeutic limits for an extended period, which supports the ongoing dosing regimen in mid-stage studies, NeuroSense reported.

Alon Ben-Noon, chief executive officer at NeuroSense told BioSpace the compounds work synergistically. By releasing them simultaneously, they work together to provide a long and sustained response in patients. The results demonstrate the favorable safety and improved PK profile of PrimeC in this unique formulation, Ben-Noon said. He added that the results support the PrimeC dosing regimen used in the current PARADIGM trial.

PrimeC has received Orphan Drug status from both the FDA as well as the European Medicines Agency.

The current formulation of PrimeC is being assessed in a Phase IIb study primarily conducted in Israel and Italy. Ben-Noon said he hopes the new PK data, along with existing toxicology studies, will entice the FDA to approve an amended Investigational New Drug application that will enable U.S.-based patients to participate in the trial. The amended IND should be submitted to the regulatory agency within the next two weeks and Ben-Noon is confident the green light will be given within a month’s time.  

“We hope to complete enrollment in the PARADIGM study by the end of the year,” he said.

Participants in the Phase IIb study will be randomized two-to-one, with two-thirds of patients receiving PrimeC. The other third will receive Riluzole, the standard-of-care treatment for ALS. The trial includes patients with both predominant types of ALS, bulbar and limb onset. Topline data is expected in the middle of 2023, Ben-Noon said. After that, all patients will be allowed to continue in a 12-month open-label extension study where only PrimeC is administered.

The topline results from the IIb study are expected to inform the design of the planned Phase III PrimeC trial.

The current PARADIGM study builds on data from a small Phase IIa study of 15 patients conducted with the previous formation of PrimeC. The data, released in 2021, showed statistically significant results that included changes in ALS biomarkers, as well as reduced functional and respiratory deterioration.

“This is a unique formulation and we’ve already seen statistically significant results with ALS biomarkers in the IIa with a much simpler formulation of PrimeC. Now, with this formulation, we expect to have much better results and we have high hopes it will provide a significant benefit to patients,” Ben-Noon said. “The synergism between the compounds is the key in order to create the required changes in the mechanisms we’re tackling.”

All Eyes on ALS 

He noted that ALS is a tricky disease to treat due to its non-linear nature. The inevitable decline of patients occurs at different rates, which is an example of its complexity, he said.

NeuroSense’s PK announcement comes a day before the FDA is set to make a decision on Amylyx’s AMX0035, another potential new therapy for ALS.

Earlier this month, an FDA advisory committee backed Amylyx’s AMX0035 in a 7-2 vote. The committee granted AMX0035 a second look after a post hoc analysis of data that showed a 10.6-month longer median survival duration for patients who received the drug. The updated median survival of 18.8 months was an improvement over the 6.9 months initially reported.

“If the FDA approves the Amylyx drug it will be a great day for ALS patients and their families,as well as for NeuroSense, as it paves an expedited development route for us, ” Ben-Noon said. He noted that the improved survival time is significantly important to patients and their families who crave that extra time.