Vistagen Wins US Patent for Investigational NMDA Receptor Antagonist to Treat Neuropathic Pain
AV-101 is an orally bioavailable small molecule NMDA receptor antagonist with antinociceptive effects similar to gabapentin but with more a more favorable safety profile.
The US Patent and Trademark Office has granted Vistagen a patent for AV-101, an investigational non-opioid oral prodrug for the treatment of neuropathic pain. Vistagen is also investigating the clinical stage drug, which modulates NMDA receptor activity, for treatment of dyskinesias and other neurologic disorders, according to a February 5, news release.1 The FDA granted Fast Track Designation for development of the oral nonopioid pain reliever in October 2018.2
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Preclinical data reported by Tony L Yaksh, PhD, professor of anesthesiology and pharmacology at the University of California, San Diego in The Journal of Pain3 demonstrated antinociceptive effects of AV-101 comparable to gabapentin, with an improved safety profile in models of hyperalgesia and allodynia, the company stated.3 Additional preclinical data from the gold-standard Chung ligation model of neuropathic pain caused by nerve damage showed the pro-drug's efficacy similar to pregabalin in neuropathic pain states. Clinical data from Phase 1 trials, published in the Scandinavian Journal of Pain,4 indicated AV-101 was well tolerated with no significant difference in adverse events compared to placebo.4While these studies were not powered to detect statistical significance in pain reduction, consistent decreases in allodynia and hyperalgesia were observed, according to Vistagen.1
AV-101 (4-Cl-KYN) is a prodrug that produces 7-Cl-KYNA, an NMDA receptor modulator distinct from classic channel-blocking antagonists like ketamine. Unlike ketamine and amantadine, which act as ion channel blockers, 7-Cl-KYNA modulates NMDA receptor function without causing the adverse psychological side effects associated with traditional NMDA receptor antagonists.1 AV-101 has demonstrated high oral bioavailability, efficient blood-brain barrier penetration, and preferential conversion to 7-Cl-KYNA in brain regions implicated in Parkinson’s disease and neuropathic pain. The company described the pharmacokinetic profile as "excellent."1
Vistagen also described an extensive receptor screening study that found no off-target binding for AV-101 or its active metabolite, suggesting a potentially favorable safety profile. In addition, phase 1 clinical trials have indicated that AV-101 is well tolerated, with no serious adverse psychological effects or safety concerns. Compared to existing non-opioid treatments such as gabapentin and pregabalin, which are associated with sedation in some patients, AV-101 may offer a safer alternative with an improved tolerability profile.1
The FDA also granted Fast Track designation to AV-101 as an adjunctive treatment for major depressive disorder, the indication being studied in the ongoing phase 2 ELEVATE clinical trials.2 Vistagen is actively seeking strategic partnerships to advance the clinical development and commercialization of AV-101 for neuropathic pain and other neurologic disorders.
According to the company, the patent extends through at least 2034 and is part of Vistagen’s broader intellectual property portfolio covering manufacturing methods and therapeutic applications of AV-101.1
