Intranasal Mebufotenin Benzoate Reduces Depressive Symptoms in TRD Patients, Phase 2b Trial Shows
Initial data from the core stage of a phase 2b clinical trial showed that an intranasal formulation of mebufotenin benzoate, BPL-003, significantly reduced depressive symptoms in patients with treatment-resistant depression (TRD) over an 8-week period, according to a joint press release from atai Life Sciences and Beckley Psytech Limited.
“What stands out in these results is that a single administration of BPL-003 in patients with treatment-resistant depression was generally well tolerated and produced a robust antidepressant effect that emerged rapidly and was solidly sustained for at least 2 months,” said David Feifel, MD, PhD, professor emeritus of psychiatry at the University of California, San Diego and director of the Kadima Neuropsychiatry Institute in the press release.
The quadruple-masked study enrolled 193 patients with moderate to severe TRD, which was defined as non-response to 2 or more prior treatments in the current depressive episode. Participants were recruited from 38 sites across 6 countries and were randomized to receive a single 12-mg (n=73), 8-mg (n=46), or 0.3-mg comparator (n=74) dose of BPL-003 over 8 weeks. Montgomery-Åsberg Depression Rating Scale (MADRS) scores were measured at day 2, day 8, day 29, and day 57 to assess treatment efficacy.
The data showed that the 8 mg dose of BPL-003 led to a mean MADRS score reduction of 12.1 points compared with just 5.8 points in the comparator arm (p=0.0025) at day 29. The 12 mg dose also significantly reduced depressive symptoms, with a mean MADRS score reduction of 11.1 points (p=0.0038) at the same timepoint. These reductions were significant as early as day 2 and continued to be significant through day 57.
BPL-003 was also well-tolerated at all doses, with no serious drug-related adverse events (AEs) reported.
An ongoing 8-week open-label extension (OLE) stage of the study is further evaluating the safety and efficacy of a second 12 mg dose administered to participants 8 weeks after dosing in the core study. Researchers hope the extension will offer greater insight into the durability of the drug’s antidepressant effect and the impact of repeat dosing.
