On 20 September, Relmada Therapeutics announced positive efficacy and safety data from a long-term, open-label, non-comparative, registrational Phase III trial (NCT04855760) for its antidepressant REL-1017 (esmethadone hydrochloride) in patients who had not previously been treated with the drug. There is a significant unmet need within the major depressive disorder (MDD) space for pharmacotherapies that can demonstrate a rapid antidepressant effect, an issue that REL-1017 is looking to address. In the trial, 26.6% of patients achieved a clinical response, defined as a ≥50% improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) total score, by Day 7, increasing to 51.0% by Month 1. Additionally, 12.1% of patients were in clinical remission, defined as MADRS total score ≤10 by Day 7, increasing to 30.1% at Month 1. Combined with its rapid onset of action, REL-1017 demonstrated sustained antidepressant effects, with 77.2% of patients achieving clinical response by Month 12 and 54.5% of patients achieving clinical remission by Month 12.

In general, the side-effect burden is high with currently available antidepressants. According to key opinion leaders interviewed by GlobalData, significant weight gain and sexual dysfunction are the most undesirable side effects of standard-of-care antidepressants such as selective serotonin reuptake inhibitors (SSRIs). By demonstrating favourable long-term tolerability without these side effects, REL-1017 could be a more appealing long-term option for patients. This could help improve treatment compliance compared with other antidepressants, potentially boosting its overall efficacy as a result.

How well do you really know your competitors?

Access the most comprehensive Company Profiles on the market, powered by GlobalData. Save hours of research. Gain competitive edge.

Company Profile – free sample

Thank you!

Your download email will arrive shortly

Not ready to buy yet? Download a free sample

We are confident about the unique quality of our Company Profiles. However, we want you to make the most beneficial decision for your business, so we offer a free sample that you can download by submitting the below form

By GlobalData
Visit our Privacy Policy for more information about our services, how we may use, process and share your personal data, including information of your rights in respect of your personal data and how you can unsubscribe from future marketing communications. Our services are intended for corporate subscribers and you warrant that the email address submitted is your corporate email address.

While these positive results are important for Relmada Therapeutics in demonstrating the efficacy of REL-1017 as an adjunctive therapy for MDD, they have come in an open-label trial. The drug will still need to demonstrate efficacy in a placebo-controlled trial, following a previous Phase III trial where the primary endpoint was missed due to a high placebo response rate (RELIANCE I: NCT04688164). Therefore, demonstrating efficacy compared to placebo in two ongoing Phase III trials that are due to be completed in 2024, RELIANCE II (NCT04855747) and RELIGHT (NCT06011577), will be crucial to REL-1017’s prospects.

If REL-1017 does enter the MDD market, it will face significant competition from Axsome Therapeutics’s Auvelity (dextromethorphan + bupropion), which was the first oral, rapidly acting antidepressant to be approved by the FDA in 2022. Like REL-1017, Auvelity demonstrated statistically significant efficacy from Week 1 of treatment and the drug was not associated with weight gain. Since Auvelity has had time to establish itself in the MDD market, if REL-1017 can demonstrate greater efficacy than Auvelity in RELIANCE II and RELIGHT, it could enhance REL-1017’s uptake despite its later start.