Studies of Relmada’s drug, esmethadone, showed the drug had lower human abuse potential when compared to ketamine. Here are the results of this study.
Esmethadone appears to be less addictive than its counterpart treatment option Ketamine.
Relmada Therapeutics, a Florida-based, late-stage biotechnology company focused on developing treatments for central nervous system diseases, announced top-line results of its study of human abuse potential (HAP) with its drug esmethadone, also called REL-1017.
This new therapy is an NMDA channel blocker developed to treat major depressive disorder (MDD). The studies stated that the drug showed HAP equivalent to the placebo and significantly lower abuse potential than ketamine.
Why is There Need for MDD Drugs Like Esmethadone?
The United States National Institute for Mental Health (NIMH) reports that in 2020, about 21 million adults suffered from at least one major depressive episode. Most patients with MDD take either selective serotonin reuptake inhibitor (SSRI) or selective norepinephrine reuptake inhibitor (SNRI) medications, but those are only somewhat effective, as approximately 31% of people being treated for MDD were classified as having treatment-resistant depression, or depression that did not respond to two or more medications.
For patients with treatment-resistant depression, ketamine has emerged as a new possible therapy. Although it has shown promising initial results, it also has worrisome addictive properties, as ketamine targets opioid receptors in the brain. This is especially dangerous for patients with MDD who struggle with substance abuse disorder.
Remalda’s previous clinical trials on esmethadone (REL-1017) showed that the drug was effective, safe and very tolerable. In a randomized, double-blind Phase II study conducted between May 2018 and August 2019, the drug showed consistently positive effects on mood in patients with treatment-resistant depression. The concern is whether the drug had addictive potential, so Remalda did more research.
In July 2021, Remalda conducted a study comparing REL-1017 to oxycodone to try and determine addictive potential. The results showed that REL-1017 was far less addictive than oxycodone and showed the same human abuse potential as a placebo, but it was still successful at treating depression. Remalda conducted a similar study to determine additive potential in REL-1017 versus ketamine, which is a much more similar treatment for MDD.
In this study, Relmada tested its new drug REL-1017, using intravenous ketamine (0.5 mg/kg over 40 minutes) as the active control drug. Patients who received esmethadone (REL-1017) received doses of 25 mg, 75 mg or 150 mg—classically used as the therapeutic, supratherapeutic and maximum tolerated doses. These doses were tested on patients who use drugs recreationally to see if different doses had different effects.
After receiving treatment, patients reported their experience of “likability” of the drug. Likability was measured on a scale from 0 to 100, with 0 being intense dislike, 50 being neutral and 100 being intensely like.
The results showed that esmethadone (REL-1017) had statistically significantly lower “likability” results than ketamine, and equivalent results to the placebo, indicating a lower HAP score and therefore less potential for drug abuse.
“We are very satisfied with the results of our second confirmatory HAP study, designed following FDA guidance, as part of the planned New Drug Application for REL-1017 for the treatment of MDD. These data are consistent with our prior oxycodone HAP study and confirm the large body of literature indicating the lack of meaningful abuse potential of REL-1017,” said Paolo Manfredi, M.D., chief scientific officer of Relmada. “There is a significant need for new treatment options for patients suffering from depression, and we continue to believe that esmethadone has the potential to be a very safe, well-tolerated and effective rapid-acting antidepressant.”
