BPL-003: Rapid, Durable Treatment for TRD Sees Positive Phase 2 Results

LAONG/AdobeStock

There are new positive initial results from Beckley Psytech’s phase 2a open label study of BPL-003—a novel, synthetic, intranasally administered benzoate salt formulation of mebufotenin—in treatment-resistant depression (TRD). A single 10 mg dose of BPL-003 resulted in rapid, durable depression symptom reduction in patients living with TRD.¹

The open-label phase 2a study investigated the safety, tolerability, and efficacy of the 10 mg dose of BPL-003 accompanied by psychological support in participants with moderate-to-severe TRD who were not taking antidepressants. During the study, 12 participants were dosed and 11 met analysis criteria. Investigators followed participants for 12 weeks after dosing and assessed them multiple times using the Montgomery–Åsberg Depression Rating Scale (MADRS). A single dose of BPL-003 induced a rapid antidepressant response in 55% of patients the day after dosing, and this effect was durable with a 55% response rate maintained at week 4 and through to week 12. By week 4, 55% of patients achieved remission, and 45% achieved remission at week 12. This clinical study is the longest known follow-up of depression outcomes for mebufotenin.

“We are thrilled with the progress the Beckley Psytech team has made on the BPL-003 program. The positive data from the phase 2a study is highly encouraging as we await the results of the larger phase 2b study anticipated later this year,” said Florian Brand, chief executive officer and cofounder of atai Life Sciences. “With around half of TRD patients in remission 3 months after just a single dose of BPL-003 in this study, we are particularly excited about its antidepressant durability potential. The results indicate that BPL-003 could offer a scalable, single-dose administration within the 2 hour in-clinic treatment paradigm successfully established by Spravato.”

The acute effects of BPL-003 resolved in less than 2 hours on average, suggesting that this treatment could offer a shorter in-clinic treatment time when compared with other in-development psychedelics.

BPL-003 was well tolerated, with predominantly mild or moderate adverse events. The most common (>10%) were nasal discomfort, headaches, nausea, and vomiting, all consistent with previous phase 1 results. No serious adverse events were reported.

BPL-003 received Investigational New Drug (IND) approval from the US Food and Drug Administration (FDA) back in February 2023, which was the first time the FDA has given IND approval for a phase 2b study of a short-acting psychedelic.²

Further research is currently underway on BPL-003. First, a part 2 extension of this study is now enrolling participants to assess the safety and efficacy of coadministered BPL-003 in individuals with TRD who take oral antidepressants (NCT05660642). Additionally, a randomized, quadruple-masked, controlled phase 2b study is in progress (NCT05870540), investigating the effects of a single 12 mg or 8 mg dose of BPL-003 against a sub-perceptual dose of 0.3 mg in 225 participants with TRD. Investigators will assess efficacy using the MADRS scale at several time points; the primary endpoint is at week 4, and final assessment is at week 8, with top-line results expected later in 2024.

References

1. atai Life Sciences announces positive initial results from Beckley Psytech’s phase 2a open label study of BPL-003 (intranasal 5-MeO-DMT) in treatment resistant depression. News release. March 27, 2024. https://ir.atai.life/news-releases/news-release-details/atai-life-sciences-announces-positive-initial-results-beckley

2. Beckley Psytech receives FDA Investigational New Drug (IND) approval for phase IIb study of BPL-003, a novel synthetic formulation of 5-MeO-DMT (mebufotenin). BioSpace. News release. February 21, 2023. Accessed March 27, 2024. https://www.biospace.com/article/releases/beckley-psytech-receives-fda-investigational-new-drug-ind-approval-for-phase-iib-study-of-bpl-003-a-novel-synthetic-formulation-of-5-meo-dmt-mebufotenin-/