This morning, Compass Pathways shared a highly anticipated topline readout that provides a first look at how patients with treatment-resistant depression (TRD) fared in its second, larger (N=581) Phase 3 study of synthetic psilocybin (COMP360).

Notably, the present study (COMP006) administered two doses of either 1 mg, 10 mg, or 25 mg of psilocybin 3 weeks apart, with the readout from this study representing the six-week primary endpoint comparing the MADRS change from baseline between 25 mg and 1 mg groups. The company also shared 26-week data from its first, smaller (N=258), placebo-controlled Phase 3 trial (COMP005).

The headline is that the readout is positive, having met the primary endpoint and demonstrating a safety profile in line with expectations. The MADRS delta is very similar to that seen in last summer’s COMP005 readout, which will be viewed by some as modest. It is worth noting, though, that the primary endpoint in this study compares the 25 mg arm to the 1 mg, versus 005’s which compared the 25 mg dose to inert placebo. As such, the absolute MADRS change versus baseline is larger in the 25 mg arm of COMP006, the company told Psychedelic Alpha, though specific figures have not been made public at the time of publication.

Many were hoping the COMP006 primary endpoint data would provide a clear picture of the incremental benefit associated with a second dose, compared to the single-dose regimen in Part A of COMP005. While today’s topline does provide signals that an additional dose of COMP360 psilocybin can deepen response in some patients, many questions also remain open, with the company’s 26-week readout from 006 expected to flesh out the profile in this regard. It’s also unclear whether patients who show no response to a first dose will find benefit in additional doses.

To dive deeper into today’s topline readout, we spoke to Compass CEO Kabir Nath and Chief Medical Officer Guy Goodwin.

In this article:

• Solid, If Not Spectacular: Two-Dose Regimen Meets Primary Endpoint
• Parsing the Incremental Benefit of Retreatment
• No New Safety Signals
• Clinical Translation: Dosing, Durability, Decision-Making
• Did Standardisation Come at a Cost?
• Commercial Implications
• The Pα Take