Relmada Therapeutics announced it would make key changes to its clinical evaluation of REL-1017 as a possible add-on treatment for major depressive disorder.
A man sits with head in hands/Courtesy of Shutterstock
Relmada Therapeutics announced it would make key changes to its clinical evaluation of REL-1017 as a possible add-on treatment for major depressive disorder (MDD), following two failed Phase III trials.
The Florida-based biotech will change the ongoing Phase III Study 302, with hopes to complete the trial by December 2023. Another ongoing study is evaluating the safety of REL-1017, with a July 2023 estimated completion date.
Relmada finalized a protocol amendment to Study 302 that will be immediately implemented.
Relmada will also launch a new trial, Study 304. The protocol for this study has been drafted and enrollment will begin by mid-2023.
The most important drivers for a successful depression trial are recruiting appropriate patients with MDD and controlling the placebo response, Relmada CEO Sergio Traversa said on a conference call Thursday.
Traversa said that identifying these issues explains why the Phase III data the company has seen has differed from its Phase II data.
The changes come after evaluating the results of Reliance I, Study 301, reported in December 2022. In this study, REL-1017, an investigational NDMA receptor channel blocker, failed to meet its primary endpoint.
REL-1017 decreased scores on the Montgomery-Asberg Depression Rating Scale by 15.1 points at the 28-day follow-up, while placebo patients saw a score drop of 12.9. This 2.2-point difference between the groups fell short of statistical significance. This marked the second Phase III flop for REL-1017 in 2022.
In October 2022, Relmada reported that its Reliance III trial had failed to hit the primary endpoint and that the results were paradoxical.
An analysis the company ran to understand the paradoxical data excluded trial sites with “implausibly high or low placebo responses” and found a meaningful difference between REL-1017 and placebo.
The placebo arm results were significantly higher, unexpected, and associated with specific trial sites.
“The prior studies had relied on self-reported medical history from the subjects regardless of the source of recruitment being verified or unverified,” Traversa said.
As a result, he said subjects had not received satisfactory vetting.
Relmada also announced the appointment of CNS therapeutics expert, Cedric O’Gorman, as its new CMO. O’Gorman pointed to changes newly made to site selection.
He said the company intends to limit the number of patients per site. This way, he said, no one site can disproportionately affect study outcomes.
Additional changes to the study protocols involve reducing the duration of site visits and assessments. O’Gorman said the company consulted with a number of experts on the subject.
“These experts concluded that site visits in Study 301 were too long with too many assessments, driving up placebo response,” he stated.
Traversa said all the pieces are now in place for a successful NDA filing for REL-1017.
FDA granted the therapy Fast Track Designation for the treatment of MDD in August 2022.
Relmada had about $148.2 million at the end of 2022. This gives the company “ample runway of approximately two years of cash,” Relmada CFO Maged Shenouda said during the call.
