Relmada's stock sinks after depression drug defeated by 'outperforming' placebo

Relmada Therapeutics’ lead asset flunked a phase 3 trial in major depressive disorder (MDD), plunging the biotech’s stock 77%.

The Reliance III trial saw 232 participants receive the therapy, dubbed REL-1017, for 28 days. The study missed its primary endpoint, with patients showing a reduction on a depression rating scale of 14.8 compared to 13.9 in the placebo cohort.

The placebo response was “higher than expected,” with certain study sites seeing placebo “dramatically outperforming” REL-1017, Relmada said in an Oct. 13 release. The company is investigating the results from the trial, which aimed to enroll 400 patients, according to its trial registry page, which was last updated May 10. 

Searching for some good news, Relmada conducted another analysis that excluded sites with implausibly high or low placebo responses. With the unwelcome data removed, the study showed what the biotech called a "meaningful difference" between REL-1017 and placebo.

It clearly wasn’t enough to satisfy investors, who sent Relmada’s stock plummeting 77%, opening Thursday at $7.25 per share.

The biotech added that the tolerability and safety of the once-daily antidepressant confirmed results from other trials, with no opioid-like withdrawal or psychotomimetic effects. REL-1017 is an opioid-inactive (S)-enantiomer of methadone.

Two other ongoing MDD phase 3 trials, Reliance I and II, are looking at REL-1017 as a potential adjunctive therapy alongside patients' ongoing antidepressant treatment. There is also Reliance-OLS, a one-year open-label safety study that is enrolling rollover participants from all three pivotal studies.

REL-1017 is designed to targets hyperactive channels while maintaining physiological glutamatergic neurotransmission. With doubts about the drug's effectiveness, Relmada's only other clinical-stage program is based on psilocybin and derivate molecules in neurodegenerative diseases, which it bought from Arbormentis last year.