Relmada Therapeutics, Inc. (RLMD), a clinical-stage company developing novel therapies for the treatment of chronic pain, announced that d-Methadone (dextromethadone, REL-1017), a N-methyl-d-aspartate (NMDA) receptor antagonist in development as a treatment for both depression and chronic neuropathic pain, has received Orphan Drug designation from the US Food and Drug Administration (FDA) for the management of postherpetic neuralgia. Postherpetic neuralgia (PHN) is a painful neuropathic condition resulting from an outbreak of the herpes zoster virus, otherwise known as shingles.
Orphan drug designation is granted by the FDA Office of Orphan Drug Products to novel drugs or biologics that treat a rare disease or condition affecting fewer than 200,000 patients in the US. The designation provides the drug developer with a seven-year period of US marketing exclusivity if the drug is the first of its type approved for the specified indication or if it demonstrates superior safety, efficacy, or a major contribution to patient care versus another drug of its type previously granted the designation for the same indication, as well as with potential tax credits for clinical research costs, the potential to apply for annual grant funding, clinical research trial design assistance and waiver of Prescription Drug User Fee Act (PDUFA) filing fees.
"The award of Orphan Drug designation for d-Methadone in the treatment of neuropathic pain is another important development in our ongoing efforts to advance this highly promising therapy to late stage clinical development and regulatory review," said Sergio Traversa, CEO of Relmada Therapeutics. "We continue to see promising results in our research with d-Methadone in neuropathic pain as we also work to advance our development plans for this compound in the treatment of depression."
In May 2016, Relmada reported positive results from an in vivo study to determine whether d-Methadone elicits antidepressant-like effects after a single administration in a well-validated animal model to predict antidepressant effects, the forced swim test. At all doses tested, d-Methadone significantly decreased immobility of the rats compared to the vehicle, suggesting antidepressant-like activity. In addition, the effect of d-Methadone on immobility at the two highest doses tested was larger than the effect seen with ketamine, a noncompetitive NMDA receptor antagonist that has been thoroughly characterized in this model and has demonstrated rapid onset of activity in several clinical studies targeting treatment of depression, but has also been shown in multiple studies to present a high risk of toxicity.
As a single isomer, d-Methadone (dextromethadone, REL-1017) has been shown to possess NMDA antagonist properties with virtually no opioid activity at the expected therapeutic doses. The activation of NMDA receptors has been associated with neuropathic pain and it is expected that REL-1017 will have a role in pain management by blocking this activity. In contrast, racemic methadone is a long-acting narcotic used in the treatment of various pain states and as a substitution therapy in opioid addiction and associated with typical opioid side effects.