Relmada Therapeutics is preparing for one last roll of the dice. After blaming the failure of its first two phase 3 trials on an “unplausible placebo response,” the depression drug developer has sifted through the ashes of the flameouts and outlined plans to start a new study.
Late last year, Relmada reported back-to-back failures of its NMDA receptor channel blocker REL-1017 in phase 3 clinical trials in major depressive disorder (MDD). The biotech flagged the high placebo response rate at some sites as a potential source of the setback after the first failure and doubled down on the hypothesis after the second flop. In Relmada’s view, the drug candidate was undone by outliers in the data set.
Since then, the biotech has continued going over the data, leading to the presentation of its new plan for getting REL-1017 to market. Relmada plans to make changes to an ongoing study and initiate a new trial in light of the lessons of the two flops.
On a conference call with investors, Cedric O'Gorman, M.D., chief medical officer at Relmada, explained that the results differed between patients who were already known to trial sites and those who learned about the study through adverts, social media and other media.
“We believe that subjects recruited through unverifiable sources were not adequately vetted via the use of medical or pharmacy records to confirm the accuracy of their MDD diagnosis. Moving forward for our trials, medical and pharmacy records are mandated regardless of source of recruitment,” O'Gorman said.
The CMO also outlined site selection improvements, noting that Relmada now has “a wealth of data” on the performance of trial centers and will “limit the number of patients per site, so no single site can have a disproportionate effect on study outcomes.”
Other changes include reductions in the duration of site visits and assessments. “We consulted with various internal and external stakeholders for additional perspective,” O'Gorman said. “These experts concluded that site visits in Study 301 were too long in duration with too many assessments, driving up placebo response.”
Study 302 has remained open for recruitment, although O'Gorman said “it was moving a little bit more slowly over the past quarter as we worked to streamline the existing protocol and make the necessary amendments.” Another study, 304, is scheduled to start around the middle of the year.
Relmada ended last year with $148.3 million, giving it “ample runway of approximately two years of cash.”