Relmada Therapeutics Announces Top-line Results from Phase 3 RELIANCE III Trial for REL-1017 as a Monotherapy for the Treatment of Major Depressive Disorder

Rhea-AI Summary

Relmada Therapeutics, Inc. (Nasdaq: RLMD) announced that its RELIANCE III study of REL-1017, aimed at treating Major Depressive Disorder (MDD), did not meet its primary endpoint of statistically significant symptom improvement compared to placebo. The treatment group showed a MADRS reduction of 14.8 points, marginally higher than the placebo's 13.9 points. Despite these disappointing results, the safety profile of REL-1017 remained favorable. Relmada continues enrollment in two ongoing Phase 3 trials (RELIANCE I and II) for REL-1017 as an adjunctive treatment for MDD.

Positive

• REL-1017 demonstrated favorable tolerability and safety with no opioid-like effects.
• The ongoing RELIANCE I and II trials may provide additional data on REL-1017's efficacy.

Negative

• RELIANCE III trial did not achieve its primary endpoint, reflecting a potential failure in demonstrating efficacy.
• Paradoxical results observed, with placebo outperforming REL-1017 in some sites.

RELIANCE I and II Adjunctive MDD Trials Continue to Advance

CORAL GABLES, Fla., Oct. 13, 2022 /PRNewswire/ -- Relmada Therapeutics, Inc. (Nasdaq: RLMD), a late-stage biotechnology company addressing diseases of the central nervous system (CNS), today announced that its RELIANCE III study (REL-1017-303), evaluating REL-1017 in the monotherapy setting for Major Depressive Disorder (MDD), did not achieve its primary endpoint, which was a statistically significant improvement in depression symptoms compared to placebo as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) on Day 28. In the study, the REL-1017 treatment arm showed a MADRS reduction of 14.8 points at Day 28 versus 13.9 points for the placebo arm, a higher than expected placebo response.  Paradoxical results were observed in certain study sites, where placebo dramatically outperformed REL-1017. Relmada is investigating the nature of these results.

REL-1017, which was administered for 28 days to 232 subjects in RELIANCE III, demonstrated very favorable tolerability and safety, confirming the results of Phase 1 and Phase 2 studies (Fava et al, 2022)¹, with no opioid-like effects, no withdrawal effects, and no psychotomimetic effects. There were no adverse events related to QTcF prolongation.

"While these RELIANCE III results are disappointing for patients, the need for new, safe and effective treatments for MDD continues to exist. We look forward to the data from the ongoing RELIANCE I and II trials of REL-1017, a potential new therapy for the adjunctive treatment of MDD." said Maurizio Fava, Psychiatrist-In-Chief, Massachusetts General Hospital and Slater Family Professor of Psychiatry, Harvard Medical School.

To better understand the paradoxical results, a post-hoc, exploratory analysis using the band-pass method (Merlo-Pich et al, 2010²) was conducted.  The band-pass analysis excludes sites with implausibly high or low placebo responses (defined as a mean decrease from baseline in MADRS10 score greater than 14 and less than 3 points) and showed a meaningful difference between REL-1017 and placebo (>4.9 points on the MADRS, p<0.05). 

Relmada continues to enroll patients in RELIANCE I and RELIANCE II, two ongoing Phase 3, placebo-controlled, pivotal studies evaluating REL-1017 as a potential adjunctive treatment for MDD. The RELIANCE development program also includes RELIANCE-OLS, a long-term open-label safety study that is enrolling rollover participants from all three pivotal studies, as well as de novo participants.

References

¹Fava M, Stahl S, Pani L, De Martin S, Pappagallo M, Guidetti C, Alimonti A, Bettini E, Mangano RM, Wessel T, de Somer M, Caron J, Vitolo OV, DiGuglielmo GR, Gilbert A, Mehta H, Kearney M, Mattarei A, Gentilucci M, Folli F, Traversa S, Inturrisi CE, Manfredi PL. REL-1017 (Esmethadone) as Adjunctive Treatment in Patients With Major Depressive Disorder: A Phase 2a Randomized Double-Blind Trial. Am J Psychiatry. 2022 Feb;179(2):122-131. doi: 10.1176/appi.ajp.2021.21020197. Epub 2021 Dec 22. PMID: 34933568.

²Merlo-Pich E, Alexander RC, Fava M, Gomeni R. A new population-enrichment strategy to improve efficiency of placebo-controlled clinical trials of antidepressant drugs. Clin Pharmacol Ther. 2010 Nov;88(5):634-42. doi: 10.1038/clpt.2010.159. Epub 2010 Sep 22.

About REL-1017

REL-1017, a new chemical entity (NCE) and novel NMDA receptor (NMDAR) channel blocker that preferentially targets hyperactive channels while maintaining physiological glutamatergic neurotransmission, is currently in late-stage development for the treatment of major depressive disorder (MDD). The ongoing Reliance Clinical Research Program is designed to evaluate the potential for REL-1017 as a rapid-acting, oral, once-daily antidepressant treatment. In a Phase 2 trial, REL-1017 demonstrated rapid, robust, and sustained antidepressant effects with statistically significant improvements compared to placebo. The Phase 2 study also showed a favorable pharmacokinetic, safety, and tolerability profile of REL-1017 consistent with results observed in previously completed Phase 1 studies.

About Relmada Therapeutics, Inc.

Relmada Therapeutics is a late-stage biotechnology company addressing diseases of the central nervous system (CNS), with focus on major depressive disorder (MDD). Relmada's experienced and dedicated team is committed to making a difference in the lives of patients and their families. Relmada's lead program, REL-1017, is a new chemical entity (NCE) and novel NMDA receptor (NMDAR) channel blocker that preferentially targets hyperactive channels while maintaining physiological glutamatergic neurotransmission. REL-1017 has entered late-stage development as an adjunctive treatment for MDD in adults. In addition, Relmada is advancing a clinical-stage program in neurodegenerative diseases based on psilocybin and select derivative molecules. Learn more at www.relmada.com.

Forward-Looking Statements

The Private Securities Litigation Reform Act of 1995 provides a safe harbor for forward-looking statements made by us or on our behalf. This press release contains statements which constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Any statement that is not historical in nature is a forward-looking statement and may be identified by the use of words and phrases such as "expects," "anticipates," "believes," "will," "will likely result," "will continue," "plans to," "potential," "promising," and similar expressions. These statements are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described in the forward-looking statements, including potential failure of RELIANCE trial results to demonstrate clinically significant evidence of efficacy and/or safety, failure of top-line results to accurately reflect the complete results of the trial, failure to obtain regulatory approval of REL-1017 for the treatment of major depressive disorder, and the other risk factors described under the heading "Risk Factors" set forth in the Company's reports filed with the SEC from time to time. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Relmada undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Readers are cautioned that it is not possible to predict or identify all the risks, uncertainties and other factors that may affect future results and that the risks described herein should not be a complete list.

Investor Contact:
Tim McCarthy
LifeSci Advisors
tim@lifesciadvisors.com 

Media Inquiries:
FischTank PR
relmada@fischtankpr.com

 

View original content to download multimedia:https://www.prnewswire.com/news-releases/relmada-therapeutics-announces-top-line-results-from--phase-3-reliance-iii-trial-for-rel-1017-as-a-monotherapy-for-the-treatment-of-major-depressive-disorder-301648190.html

SOURCE Relmada Therapeutics, Inc.

FAQ

What were the results of the RELIANCE III study for RLMD?

The RELIANCE III study for RLMD did not meet its primary endpoint, showing a MADRS reduction of 14.8 for REL-1017 versus 13.9 for placebo.

What is the purpose of the ongoing RELIANCE I and II trials for RLMD?

The RELIANCE I and II trials are evaluating REL-1017 as a potential adjunctive treatment for Major Depressive Disorder.

What safety profile does REL-1017 have according to the press release?

REL-1017 showed favorable tolerability and safety, with no opioid-like effects, withdrawal symptoms, or QTcF prolongation.

What implications do the negative results of the RELIANCE III study have for RLMD?

The failure to meet the primary endpoint in the RELIANCE III study may impact investor confidence and the potential market entry of REL-1017.