Following the news that Relmada Therapeutics’ antidepressant REL-1017 demonstrated rapid and sustained therapeutic effects in an open label, registrational Phase III trial (NCT04855760);

Philippa Salter, Senior Neurology Analyst at GlobalData, offers her view:

“Whilst these positive results are important for Relmada Therapeutics in demonstrating the efficacy of REL-1017 as an adjunctive therapy for major depressive disorder (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 the two ongoing Phase III trials due to complete in 2024, RELIANCE II (NCT04855747) and RELIGHT (NCT06011577), will be crucial to the prospects of REL-1017.

“There is a significant unmet need within the MDD market for pharmacotherapies that can demonstrate rapid antidepressant effect, an issue which REL-1017 is looking to address. Combined with its sustained effects on depression symptoms, with just over 50% of patients achieving clinical remission at 12 months, REL-1017 has the potential to see strong uptake in the MDD market.

“In general, the side-effect burden is high with currently available antidepressants. By demonstrating favorable long-term tolerability with no significant weight gain or sexual dysfunction, the most undesirable side-effects of standard of care antidepressants highlighted by key opinion leaders interviewed by GlobalData, REL-1017 could be a more appealing long-term option to patients. This could help improve treatment compliance compared with other antidepressants, potentially boosting its overall efficacy.

“However, if REL-1017 does enter the MDD market, it will face significant competition from Axsome Therapeutics’ Auvelity (dextromethorphan + bupropion), which was the first oral, rapidly acting antidepressant to be approved by the FDA in 2022.”