ALS Combination Therapy PrimeC Receives FDA’s Orphan Drug Designation, Enters Clinical Trials

PrimeC, a new combination treatment by NeuroSense Therapeutics to slow down or halt the progression of amyotrophic lateral sclerosis (ALS), has received orphan drug status from the U.S. Food and Drug Administration (FDA), and is being investigated in two recently-initiated clinical trials.

The decision to begin the trials was due to positive results in preclinical studies, in which zebrafish with different ALS-causing mutations were given the PrimeC treatment. The treated fish significantly regained the ability to swim, with a stronger recovery than had been previously demonstrated using the same experimental model.

Researchers also observed that PrimeC contributed to a property called neuroprotection, or the preservation of cellular structure and function in the nervous system, when analyzing specific neurons, neuron-muscle connections, and the immune system of treated fish.

With the promising preclinical results, NeuroSense has launched two clinical trials to investigate PrimeC in humans. The trials are recruiting 45 ALS patients in total, with 15 patients each at three different sites: the Tel-Aviv Sourasky Medical Center (TASMC) in Tel-Aviv, Israel, The Barrow Neurological Institute (BNI) in Phoenix, Arizona, and The Neurological Institute at Columbia University in New York.

According to available information, the TASMC and BNI sites are actively recruiting adult patients at this time, and the Columbia University site is active but not recruiting.

The Phase 1 clinical trial (NCT04090684) at the two U.S. sites and the Phase 2a clinical trial (NCT04165850) at the Israeli site are investigating the safety, tolerability, and efficacy of PrimeC in ALS patients.

Safety and tolerability will be evaluated by adverse reactions and any premature cessation of the treatment. Efficacy will be measured by monitoring the progression of ALS symptoms — using the ALS Functional Rating Scale Revised score and the respiratory function assessment vital capacity — and the levels of an ALS biomarker, pNFH, in the blood.

Patients enrolled in the clinical trial will take PrimeC for 15 months. The dosage is different for the two studies, as the Israeli site will have patients taking three capsules daily, while at the U.S. sites, dosing will be twice daily.

“PrimeC, developed by NeuroSense, was shown to be very successful in preclinical studies and we are glad to be testing it in our clinic now, hopeful to see how it will affect the patients,” Vivian Drory, MD, a leading ALS researcher conducting the TASMC trial, said in a press release.

Jeffrey Shefner, MD, PhD, chair of neurology at BNI, added, “PrimeC has intriguing preclinical data and we expect a good safety profile. It is gratifying to be able to offer this novel experimental therapy to patients.”

The PrimeC treatment is a combination approach that utilizes two agents, ciprofloxacin and celecoxib, to treat two major components of ALS disease progression: inflammation of the nervous system and the improper regulation of RNA behavior. Ciprofloxacin is a prescription antibiotic traditionally used to treat bacterial infection, and celecoxib is a prescription non-steroidal anti-inflammatory drug, like aspirin and ibuprofen.

The FDA’s orphan drug status means that PrimeC is considered important enough to pursue development, but that the target disease is rare enough that the development and production of the treatment would not be profitable without governmental assistance. The status allows manufacturers to qualify for various incentives, including seven years of market exclusivity, increased support from the FDA, and special fee exemptions and reductions.

“We are excited by the potential PrimeC holds to benefit ALS patients. We are pleased to be evaluating it in these patients, providing them hope while testing the drug’s efficacy,” said Alon Ben-Noon, the CEO of NeuroSense.

“The special connection the company has with patients and their families contributes to the way we progress in our development, and we are thankful for this opportunity. We hope and expect to see positive interim results within several months.”

To continue advancing PrimeC development, NeuroSense is planning to initiate a study in healthy volunteers to determine how the treatment behaves in the body, in terms of absorption, distribution, metabolism, and excretion. The trial is expected to begin this year in Canada.

Once the study is completed and preliminary data from the ongoing trials are available, the company intends to initiate a one-year Phase 2/3 trial to study PrimeC versus a placebo in people with familial and sporadic ALS. The trial is planned to include 150 to 200 participants, and may lead to PrimeC’s conditional approval in the U.S.

The aim is to fully develop PrimeC as an effective treatment within four years.