Relmada Therapeutics’ REL-1017 in depressive disorder did not reach endpoint

Relmada Therapeutics announced results of the RELIANCE I study evaluating REL-1017 as an adjunctive treatment for Major Depressive Disorder. The same factors that negatively affected the results from the RELIANCE III study, a limited number of high enrolling sites with unplausible placebo response, also affected RELIANCE I and the study did not achieve its primary endpoint, which was a statistically significant improvement in depression symptoms compared to placebo on Day 28. RELIANCE I evaluated the use of REL-1017 in addition to a standard antidepressant for patients who had inadequate response to at least one and up to three standard antidepressant therapies. In the study, the REL-1017 treatment arm showed a MADRS reduction of 15.1 points at Day 28 versus 12.9 points for the placebo arm, which is a clinically meaningful difference of 2.2 points on the MADRS, as well as a statistically significant difference in the response rate, with a response rate of 27.2% on placebo vs 39.8% in the REL1017 arm. As observed in the monotherapy study RELIANCE III, implausible results were again observed in two of the same high enrolling RELIANCE I study centers, where placebo dramatically outperformed REL-1017. A limited number of the same high enrolling centers had implausible rapid and sustained placebo response rates that outperformed REL1017. In a post-hoc analysis of RELIANCE 1 that excluded the same two high enrolling centers that showed implausible placebo response in both REL-1017 studies, the REL-1017 treatment arm showed a MADRS reduction of 16.7 points at Day 28 versus 12.6 points for the placebo arm, a 4.1 point difference, with a pless than0.02. REL-1017 demonstrated very favorable tolerability and safety in RELIANCE I, again confirming the results of Phase 1 and Phase 2. Relmada continues to enroll patients in RELIANCE II, the second ongoing Phase 3 study evaluating REL-1017 as a potential adjunctive treatment for MDD. Relmada is applying several protocol and operational changes to RELIANCE II.