BLP-003 for Treatment-Resistant Depression: Phase 2b Patient Enrollment Completed

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atai Life Sciences announced the completion of patient enrollment in an 8-week, double-blind, core stage of the global phase 2b clinical trial evaluating mebufotenin benzoate (BPL-003) in patients with treatment-resistant depression (TRD). BPL-003 is Beckley Psytech’s patented intranasal formulation of mebufotenin benzoate, which is administered via a nasal spray device used in a previously approved drug product. BPL-003 is designed to deliver rapid and durable effects in a single dose and a short time in clinic.

“We are impressed by the Beckley Psytech team’s execution of the phase 2b clinical trial of BPL-003 in patients with TRD, which is the largest controlled trial of mebufotenin and the first and only phase 2b clinical trial to investigate mebufotenin in the US,” stated Srinivas Rao, MD, PhD, chief executive officer and cofounder of atai. “The promising data from earlier clinical studies of BPL-003 have demonstrated that a single dose can induce rapid, significant, and lasting antidepressant effects, further reinforcing our confidence in its potential to revolutionize treatment for difficult-to-treat depression. We look forward to the topline results from the 8-week core stage of the phase 2b clinical trial of BPL-003, which remains on track for mid-2025.”

The 8-week, quadruple-masked, dose-finding, core stage of the phase 2b clinical trial (NCT05870540) enrolled 196 patients with moderate-to-severe depression that failed to respond to at least 2 or more prior treatments in the current episode of depression across 38 sites in 6 countries. The trial will evaluate the efficacy and safety of a single medium (8 mg) or high (12 mg) dose of BPL-003 against a subperceptual dose. Patients are followed for 8 weeks, and efficacy is assessed at various timepoints by centralized, blinded raters using the Montgomery-Asberg Depression Rating Scale (MADRS).

There is also an 8-week, open-label, extension stage of the phase 2b clinical trial that continues to enroll patients to evaluate the safety and efficacy of a second high dose of BPL-003 administered after the completion of the core stage of the trial.

Data from the phase 2b clinical trial will be used in conjunction with the phase 2a study data of BPL-003 in patients with TRD to support end-of-phase 2 meetings with regulatory bodies. It will also assist in phase 3 planning in the second half of 2025. Initial phase 2a data showed that just a single 10 mg dose of BPL-003 produced a rapid and lasting antidepressant effect, with 55% of patients meeting the criteria for remission (MADRS ≤10) at day 29 and 45% meeting the criteria for remission at day 85. BPL-003 required a short time in clinic, with patients deemed dischargeable within an average time of less than 2 hours after dosing.

Topline results from the core stage of the phase 2b clinical trial are expected in mid-2025.

Beckley Psytech is also exploring BPL-003 as a potential treatment for alcohol use disorder (AUD). In late January, the company announced positive topline results from their open-label phase 2a study of BPL-003 in participants with moderate-to-severe AUD. Investigators noted that treatment with BPL-003 induced meaningful and sustained reductions in alcohol use and heavy drinking days for up to 3 months following a single dose.²

References

1. atai Life Sciences announces completion of enrollment in phase 2b clinical trial evaluating BPL-003 for treatment-resistant depression. News release. March 5, 2025. https://ir.atai.life/news-releases/news-release-details/atai-life-sciences-announces-completion-enrollment-phase-2b

2. Kuntz L. BPL-003 for alcohol use disorder: positive topline results of phase 2a study. Psychiatric Times. January 28, 2025. https://www.psychiatrictimes.com/view/bpl-003-for-alcohol-use-disorder-positive-topline-results-of-phase-2a-study