Relmada rails against depression data both ‘implausible’ and ‘unplausible’ in latest phase 3 flunk

Relmada rails against depression data both ‘implausible’ and ‘unplausible’ in latest phase 3 flunk

Relmada Therapeutics’ REL-1017 has failed another phase 3 depression clinical trial. And, like last time, the biotech has blamed everything but the drug candidate, pinning the failures on “a limited number of high enrolling sites with unplausible placebo response.”

In October, Relmada reported the failure of its NMDA receptor channel blocker to improve scores on a depression severity scale compared to placebo. The biotech noted “paradoxical results” at certain study sites, “where placebo dramatically outperformed REL-1017,” and shared a post hoc analysis that found the drug improved outcomes when those outliers were removed from the dataset.

Now, Relmada is back with a similar and, if anything, more vociferous rebuttal of the findings of a second phase 3 trial. Like the earlier study, the second, 227-subject trial found REL-1017 was no better than placebo at improving depression scores, causing it to miss the primary endpoint.

Overall, Relmada saw a 15.1-point reduction in depression severity in the REL-1017 arm at Day 28 versus a 12.9-point reduction in the placebo group. The biotech called the reduction “clinically meaningful,” but it fell short of the bar needed for the study to hit its primary endpoint. As Relmada sees things, the failure reflects the placebo data generated at certain sites.

In a statement that calls the results “implausible” four times and “unplausible” once, Relmada made the case that its RELIANCE I study was undone by data from two high-enrolling sites. In both trials, placebo “dramatically outperformed REL-1017” at the sites, according to Relmada.

Removing 26 patients who received placebo at the sites from the analysis caused the depression scale reduction in the control group to slip from 12.9 points to 12.6 points. The REL-1017 reduction went from 15.1 points to 16.7 points when Relmada removed 16 patients who received the drug at the sites from the analysis, giving the post hoc analysis a p-value of less than 0.02.

A third study of REL-1017 is ongoing, and Relmada is “applying several protocol and operational changes … and making certain improvements to how the trial is being conducted” in light of the two failed trials. Investors are skeptical. Shares in the biotech fell 41% to $2.45 in response to the latest failure. The stock traded above $30 before the first phase 3 failure.

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