Key Takeaways
- Relmada Therapeutics has terminated its license agreement for esmethadone after failing multiple phase 3 depression trials.
- The company is now seeking strategic alternatives, including potential mergers or asset acquisitions.
- Relmada plans to focus on advancing its other therapies, NDV-01 and sepranolone, in ongoing clinical trials.
Relmada Bids Farewell to Esmethadone
Relmada Therapeutics, based in Florida, has officially given up on its experimental treatment, esmethadone, after facing a series of setbacks in clinical trials. On July 7, the company terminated its licensing agreement for the drug, known as REL-1017, with all obligations set to conclude by October 5.
Esmethadone, a derivative of methadone traditionally used for pain management and substance use disorders, underwent several phase 3 trials focused on major depressive disorder (MDD). However, the results proved disappointing across the board. The first major setback came in October 2022 when esmethadone failed to outperform a placebo in the RELIANCE III trial, which evaluated it as a standalone MDD treatment.
The following year, a similar outcome emerged from the RELIANCE I trial, where esmethadone was tested as an adjunctive treatment. Relmada attributed this failure to an inadequate number of high-enrolling sites, which resulted in a seemingly implausible placebo response.
Despite some improvement noted in a 2023 open-label trial, which indicated a positive impact on depression symptoms, the lack of a placebo arm means these findings lack robust validation. The issues continued when Relmada disclosed in December 2024 that the RELIANCE II trial was unlikely to meet its primary endpoint. As a result, the company discontinued this trial along with another related study, RELIGHT, and announced plans to explore strategic alternatives such as a merger or sale.
The licensing deal for esmethadone was initially struck in January 2018 with researchers Charles Inturrisi and Paolo Manfredi, costing Relmada an upfront fee of $180,000, along with ongoing quarterly payments. Inturrisi, a pharmacologist at Cornell University, originally developed esmethadone. However, Relmada’s challenges with this drug have shifted its strategic focus.
Now, Relmada is concentrating on potential asset acquisitions and is advancing other projects, including NDV-01 and sepranolone. NDV-01 is currently undergoing an open-label phase 2 trial for non-muscle invasive bladder cancer, while sepranolone, which targets Tourette syndrome, is also in phase 2 trials following its acquisition from Asarina Pharma in February.
Relmada’s pivot reflects the volatile nature of drug development, especially in the challenging landscape of mental health therapies. The company’s commitment to exploring alternative paths showcases its resilience in the face of setbacks and underscores its intent to continue advancing in the biotech arena.
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