COMP360 Psilocybin NDA Submitted to FDA for Treatment-Resistant Depression

Compass Pathways has completed its New Drug Application (NDA) submission to the US Food and Drug Administration (FDA) for COMP360 psilocybin in treatment-resistant depression (TRD), supported by 3 positive trials in > 1000 participants.¹

The company announced the completed submission on November 9, 2026, following a rolling submission and review process and the award of a National Priority Voucher, which Compass Pathways said may accelerate the FDA review.¹ According to Compass Pathways, an estimated 4 million people in the US live with TRD, and < 5% currently receive a TRD-indicated treatment.¹ COMP360 contains a Schedule I controlled substance, so the US Drug Enforcement Administration (DEA) and individual states must reschedule it before commercialization, if approved.¹

"Compass is leading the development of this new class of medicines with rigor and discipline, successfully completing the largest late-stage clinical program in psychedelic treatments," said Kabir Nath, chief executive officer of Compass Pathways. "We look forward to continuing the review process, and we are focused on delivering COMP360 to patients as quickly as possible, subject to FDA approval."¹

COMP360 Efficacy in the COMP005 and COMP006 Phase 3 Trials

The randomized, double-blind, placebo-controlled phase 3 COMP005 trial enrolled 258 participants in the US, who received a single 25-mg dose of COMP360 (n = 171) or placebo (n = 87).² The 25-mg dose reduced Montgomery-Åsberg Depression Rating Scale (MADRS) total score by 3.6 points compared with placebo at week 6 (95% CI, –5.7 to –1.5; P <.001).³ According to Compass, 25% of participants in the 25-mg arm achieved a clinically meaningful MADRS reduction (≥25%) after a single dose.²

The randomized, double-blind phase 3 COMP006 trial dosed 581 participants across North America and Europe, who received 2 fixed doses of COMP360 25 mg (n = 296), 10 mg (n = 142), or 1 mg (n = 143) administered 3 weeks apart.² The 25-mg dose reduced MADRS total score by 3.8 points compared with the 1-mg dose at week 6 (95% CI, –5.8 to –1.8; P <.001). ³

In the 25-mg arm, 39% of participants achieved a clinically meaningful MADRS reduction (≥25%) at week 6, with benefit maintained on average through at least week 26.² Nearly 30% of week 6 responders reached remission (MADRS ≤12) after retreatment in Part B, according to the company.² Participants in COMP006 had a current depressive episode lasting > 3 years on average and more than 6 lifetime episodes.²

COMP360 Safety Profile Across the Phase 3 Program

Through 26 weeks of COMP006, serious adverse events occurred in 5.7% of participants in the 25-mg arm and 6.3% of participants in the 1-mg arm.² The most common adverse events included nausea, headache, anxiety, and visual hallucination.² Compass reported most treatment-emergent adverse events were transient and occurred predominantly on the day of dosing, with no new safety findings.²

At the week 6 primary analysis, serious adverse events occurred in 5% of participants in COMP005. ³ Suicidal ideation occurred in < 1% of participants across studies, and the single suicidal behavior event in COMP006 occurred in the 1-mg arm. ³ An independent Data Safety Monitoring Board reported no new or unexpected safety signals based on the available data. ³

Both trials include an open-label Part C running from week 26 to week 52.² The NDA also draws on the phase 2b trial published in The New England Journal of Medicine, in which 233 participants received a single 25-mg, 10-mg, or 1-mg dose of COMP360 alongside psychological support.⁴ In the phase 2b study, the 25-mg dose produced a significantly greater reduction in MADRS score compared with the 1-mg dose at week 3, and suicidal ideation and intentional self-injury were observed across all dose groups.⁴

COMP360 holds Breakthrough Therapy designation from the FDA and Innovative Licensing and Access Pathway designation in the UK for TRD.¹ Compass is also running a late-stage trial of COMP360 in post-traumatic stress disorder (PTSD) and expects to launch COMP360 for TRD in the first half of 2027, subject to FDA approval.¹

References

1. Compass Pathways Completes COMP360 Psilocybin New Drug Application To U.S. FDA For Treatment-Resistant Depression. Compass Pathways. Published November 9, 2026. Accessed November 9, 2026. https://ir.compasspathways.com/News--Events-/news/news-details/2026/Compass-Pathways-Completes-COMP360-Psilocybin-New-Drug-Application-to-U-S--FDA-for-Treatment-Resistant-Depression/default.aspx

2. Compass Pathways Announces Six-Month Data From Second Phase 3 Trial Confirming Rapid And Durable Profile. Compass Pathways. Published July 7, 2026. Accessed November 9, 2026. https://www.businesswire.com/news/home/20260707713443/en

3. Derman C. COMP360 Psilocybin Meets Primary Endpoint In Second Phase 3 Trial For TRD. HCPLive. Published February 19, 2026. Accessed November 9, 2026. https://www.hcplive.com/view/comp360-psilocybin-meets-primary-endpoint-second-phase-3-trial-trd

4. Goodwin GM, Aaronson ST, Alvarez O, et al. Single-Dose Psilocybin For A Treatment-Resistant Episode Of Major Depression. N Engl J Med. 2022;387(18):1637-1648. doi:10.1056/NEJMoa2206443