Nerve Repair Therapy NVG-291 Safe, Well-tolerated in Healthy People

A single dose of NVG-291, a potential nerve repair therapy for multiple sclerosis (MS), was safe and well-tolerated among healthy volunteers in a Phase 1 safety trial, and was found to have favorable pharmacological properties, new data show.

Given the positive results thus far, a safety committee supervising the study has recommended that NervGen, the therapy’s developer, begin the multiple ascending dose (MAD) phase of the trial. To date, the single ascending dose (SAD) part of the trial has been completed across six dosing groups, the company said.

The data on the Phase 1 program was presented at the Neuroscience 2021 Preview Days, leading up to the Society for Neuroscience’s annual conference, being held entirely virtually Nov. 8–11.

The results, which are still blinded — meaning that researchers don’t know which patients were taking NVG-291, and who received a placebo — were presented by Daniel Mikol, MD, PhD, NervGen’s chief medical officer.

“The data that we presented is very encouraging as all adverse events reported in the study were mild and transient,” Mikol said in a press release.

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Taking place in Australia, the Phase 1 study is evaluating NVG-291 in 37 healthy volunteers who participated in six groups, each given a higher dose of the medicine, or a placebo. All adverse events were mild and short-lived, and there were no observed effects on vital signs, electrocardiogram heart tests, or lab assessments.

Participants were dosed as high as 0.864 mg/kg, which, when using dose conversion models, was 170% higher than the highest effective dose studied in the various animal models of nervous system injury. In those animal models, the doses ranged from 0.01 to 0.32 mg/kg.

“We have tested doses in the SAD of the study that are substantially higher than the dose equivalents used in various animal efficacy studies, and for the highest SAD dose cohort, over 100x higher than the lowest effective dose in animal models,” Mikol said.

“This wide safety margin provides flexibility as we move into the MAD portion of the study, and eventually into Phase 1b/2 clinical trials with patients,” he added.

The therapy also demonstrated favorable characteristics based on pharmacokinetic tests, which measured how the medicine is absorbed into the body and distributed, metabolized, and removed from the body.

In the MAD portion of the trial, three groups are expected to randomly receive increasing NVG-291 doses, or placebo, daily for 14 consecutive days. Results are projected for early 2022.

Supported by this positive safety data, NervGen plans to launch a Phase 1b/2 clinical trial in people with MS next year. In addition, the company is planning a Phase 1b/2a study in people with Alzheimer’s disease and a Phase 1b/2 trial in spinal cord injury patients, both expected to launch next year.

In MS, an altered immune attack damages the fatty coating around nerve fibers known as the myelin sheath, which enhances electrical signals in the body. All currently approved MS treatments work by suppressing the immune system and reducing myelin damage.

By contrast, NVG-291 is designed to promote the repair and regeneration of lost myelin. The investigational therapy works by modulating an enzyme called tyrosine phosphatase sigma. This enzyme normally blocks nerve repair following injury, either due to trauma or disease-specific processes such as MS or Alzheimer’s disease.

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Previous preclinical studies demonstrated that NVG-291 promoted the regeneration of damaged nerves and improved their function via repair mechanisms, including nerve fiber regeneration, remyelination, and lessened inflammation.

“These results continue to exceed our expectations. Not only is NVG-291 well tolerated, the positive pharmacokinetic characteristics that were reported previously appear to be maintained at the highest dose,” said Paul Brennan, NervGen’s president and CEO.

“We believe that this data provides us with very strong rationale to proceed to the MAD portion of the study, and provides us with a great deal of confidence that the efficacy results seen in multiple preclinical disease and injury models will translate to positive results in our upcoming clinical trials in Alzheimer’s disease, multiple sclerosis and spinal cord injury patients which we plan to start in 2022,” he said.

The company is also conducting ongoing toxicology studies at the request of the U.S. Food and Drug Administration, which had placed a partial clinical trial hold on NVG-291’s trials. Following these studies, NervGen will seek to remove the hold. It also plans to begin bridging studies to confirm the safety data in healthy men and premenopausal women prior to next year’s planned clinical trials.