NervGen Completes Dosing Another Group With MS Candidate NVG-291

Dosing of NVG-291, NervGen Pharma’s investigational therapy for multiple sclerosis (MS) and other nervous system diseases, was completed in the third and final group of healthy postmenopausal women in a Phase 1 clinical trial.

“Completing the dosing of the final [group] of postmenopausal females in the MAD [multiple ascending dose] portion of the Phase 1 clinical trial is an important accomplishment,” Bill Radvak, NervGen’s executive chairman and interim CEO, said in a press release.

The next step in the Phase 1 trial (NCT05308953) is to test NVG-291 in healthy men and premenopausal women, who are already being enrolled; more information on contacts and locations is available here.

These two groups of participants previously were excluded from recruitment due to a partial clinical hold placed in March 2020 by the U.S. Food and Drug Administration (FDA). That decision came after findings of adverse dose-dependent reproductive organ toxicity in preclinical studies of the therapy.

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After presenting the agency data from requested follow-up safety preclinical studies, which did not show adverse toxicity effects in the animals’ reproductive organs or fertility, NervGen was cleared to include these two groups of participants in the trial.

“Coupled with the FDA’s authorization to proceed with enrollment of male and premenopausal female bridging cohorts, we look forward to completing the Phase 1 study,” Radvak said.

NervGen is a biotech company aiming to develop therapies that allow the nervous system to repair itself after damage, whether caused by an injury or disease.

NVG-291 is a first-in-class treatment that targets the activity of a receptor protein called protein tyrosine phosphatase (PTP) sigma, which normally acts to “put the brakes” on pathways involved in nerve cell repair after damage.

By modulating PTP signaling, the therapy is expected to promote several mechanisms of nervous system repair, including remyelination — restoration of the myelin sheath surrounding nerve fibers that is progressively lost or damaged in MS.

Administered through under-the-skin injections, the therapy is currently being developed for MS, Alzheimer’s disease, and spinal cord injuries.

In preclinical studies, NVG-291’s rodent form — NVG-291-R — was shown to promote the restoration of the nervous system and functional recovery in animal models of MS, spinal cord injury, peripheral nerve injury, and stroke.

Study goals

The ongoing Phase 1 trial is evaluating the safety, pharmacokinetics, and immunogenicity of single and multiple increasing doses of NVG-291 in healthy volunteers recruited at its single Australian site.

Pharmacokinetics refers to the therapy’s movement into, through, and out of the body, while immunogenicity measures the drug’s ability to trigger immune responses.

In its first part, 37 healthy participants received a single under-the-skin injection of either one of six doses of NVG-291 or a placebo. Some of these doses were already higher than those tested and deemed effective in animal models.

Data from this portion showed that the therapy was generally safe and well-tolerated, prompting the initiation of the multiple dosing portion. This second part of the trial tested three doses of NVG-291 against a placebo, administered daily for 14 consecutive days.

All three doses exceeded “the corresponding doses that resulted in significant functional improvements in animal models of nervous system damage,” Radvak said.

Previous findings from the first two doses tested supported NVG-291’s favorable safety profile and the trial’s advancement to its third dose group, which has now completed dosing.

Dosing new groups

Now, similar doses will be given to the new groups of men and premenopausal women.

“NVG-291 will be administered as a once-a-day injection for 14 days, and the safety of subjects will be evaluated throughout the treatment phase and one week after the final dose of the study drug, as in the MAD,” said Daniel Mikol, MD, PhD, NervGen’s chief medical officer.

Combined data from healthy men and postmenopausal and premenopausal women are expected to help establish the optimal dose or dose range for clinical testing in future patient trials.

The company is currently in a strong cash position, thanks to equity proceeds of more than $22 million and an awarded grant of up to $1.5 million to fund ongoing clinical and preclinical activities.

This financial status will allow “us to complete the Phase 1 trial and then proceed to a spinal cord injury Phase 1b/2a study in which we administer our drug to patients,” Radvak said.

“While we are steadfastly focused on initiating the clinical trial for spinal cord injury as soon as possible, we remain committed to advancing our other priority indications that include Alzheimer’s disease and multiple sclerosis,” Radvak added.