Biopharmaceutical company atai Life Sciences has announced positive data from a proof-of-concept study investigating a two-dose induction regimen of BPL-003 (intranasal mebufotenin benzoate) in patients with treatment-resistant depression (TRD). 

The open-label Phase IIa study (NCT05660642) enrolled 13 patients with TRD who were not on concurrent antidepressants, and 12 met the criteria for per-protocol analysis. Patients were given an 8mg dose of BPL-003 followed by a 12mg dose two weeks later. Safety, tolerability and efficacy assessments were conducted at various timepoints for 12 weeks following the initial dose using multiple validated depression rating scales, including the MADRS (Montgomery-Asberg Depression Rating Scale). 

The results found that, following the first 8mg dose, patients experienced a mean MADRS reduction of 13.3 points from baseline at day two and a mean MADRS reduction of 12.9 at day eight. One week after the second dose (12 mg), there was a further decrease in MADRS score to a total of a 19.0-point reduction from baseline, with sustained antidepressant effects observed through week 12. 

The trial also showed an improved response and remission rate, with remitter rates at 42% at week 12, as well as a strong and consistent tolerability profile. Patients also met discharge readiness criteria within two hours after dosing for both doses, reinforcing the potential for BPL-003 to be integrated into the established interventional psychiatric treatment paradigm. 

The results demonstrate that a second dose of BPL-003 at week two has the potential to induce greater antidepressant effects, as evidenced by additional reductions in MADRS scores, without impact on the safety and tolerability profile of the treatment. 

More data expected in October 

Cosmo Feilding Mellen, Chief Executive Officer and Co-Founder of Beckley Psytech, said: “These results underline BPL-003’s potential to offer a rapid, well-tolerated and durable treatment option for patients with treatment-resistant depression. They suggest that a second dose of BPL-003 not only maintains, but potentially deepens, antidepressant effects while remaining well-tolerated.”  

“Importantly, the findings are consistent with results from earlier Phase IIa cohorts, including studies in patients who were taking antidepressants (SSRIs), where a single dose of BPL-003 produced rapid and sustained improvements for up to three months. Together with the results from our Phase IIb programme, these data provide a strong foundation of evidence to design our Phase III programme, and we are grateful to the patients, investigators and sites who have made this progress possible.” 

Dosing and follow-up in the open-label extension (OLE) of the Phase IIb study, which is evaluating the effects of a 12 mg dose of BPL-003 administered eight weeks after the initial dose in the core study, is complete and data are expected in October. 

 

 

Bruno Quinney, Content Team, DDW