Intranasal 5-MeO-DMT Clinical Trial Offers Hope For Treatment-Resistant Depression

Partners Beckley Psytech and atai Life Sciences ATAI have jointly announced positive initial results from a Phase 2a study of Beckley's novel formulation of 5-MeO-DMT in Treatment Resistant Depression (TRD.) 

See: Atai Invests $50M In Beckley Psytech For Short-Duration Psychedelics Development

BPL-003 is a synthetic and patent-protected benzoate salt formulation of 5-MeO-DMT (aka mebufotenin) designed for intranasal administration. The open-label study assessed safety, tolerability and efficacy of the compound at a single 10mg dose, alongside psychological support, in patients with moderate-to-severe TRD (who withdrew from concomitant antidepressants.) 

The study's initial findings reflect treatment of 11 participants, who were followed for 12 weeks post-dosing. Efficacy was assessed using the widely known and accepted Montgomery–Åsberg Depression Rating Scale (MADRS.)

The single 10mg dose resulted in a rapid onset and durable antidepressant effect in patients with TRD, which affects approximately 100 million people worldwide. Importantly, these findings are believed to represent the longest known follow-up of depression outcomes in a clinical study of 5-MeO-DMT.

Specifically:

• BLP-003's single dose induced a rapid antidepressant response in 55% of patients on the day after dosing. The antidepressant effect lasted, with a 55% response rate maintained at Week 4 and further on to Week 12. 
• 55% of patients were in remission at Week 4, and 45% in remission at Week 12. 
• BPL-003 showed a good safety profile and was well tolerated. Adverse events (AEs) were predominantly mild or moderate and the most common AEs (>10%) were nasal discomfort, headaches, nausea and vomiting, broadly consistent with Phase 1 findings. No serious AEs were reported.
• Acute effects resolved on average in less than two hours. 
• Altogether, data suggest BPL-003 could offer a shorter in-clinic treatment time vs. other psychedelic treatments in development.

Management Comments & Next In Progress

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Beckley Psytech's CEO Cosmo Feilding Mellen said the team is thrilled with the evidence that a single dose of BPL-003 delivered a rapid and durable antidepressant response in patients with TRD. 

"Our single dose treatment model enables a short treatment duration which positions BPL-003 as a potentially exciting and scalable treatment opportunity," said Feilding Mellen, adding that less than 15% of patients with TRD achieve long-term remission with the current standard of care. 

A randomized, quadruple-masked, controlled Phase 2b study of BPL-003 is currently underway. Its aim is to investigate the effects of a single 12mg or 8mg dose, vs. a sub-perceptual dose of 0.3mg, in 225 patients with TRD. 

Efficacy will be assessed by masked raters using the MADRS scale at several time points, the primary endpoint at Week 4 and final assessment at Week 8. Topline results are expected in the second half of 2024.

"We look forward to further validating the potential of BPL-003 as a treatment option with our ongoing Phase IIb study and subsequent clinical development program," Feilding Mellen concluded.

On atai's end, CEO and co-founder Florian Brand highlighted the company's particular excitement over BLP-003's antidepressant durability potential. 

"The results indicate that BPL-003 could offer a scalable, single-dose administration within the two hour in-clinic treatment paradigm successfully established by Spravato," Brand said, to later be echoed by founder and chairman Christian Angermayer. 

Separately, a Part 2 extension of Beckley's Phase 2a open-label study is now enrolling patients with TRD who are on stable doses of oral antidepressants to assess the safety and efficacy of BPL-003 co-administration.

Photo: Benzinga edit with photos by Nynke van Holten on Shutterstock and Harbin on Wikimedia Commons.

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