Lars Christian Wilde remembers the question. As a co-founder of Compass Pathways, he heard it from every investor, clinician, and regulator who looked at psilocybin’s early data: “Fine, it works acutely, but how long does it last?” That question has functioned for years as the polite version of a more aggressive skepticism, the one that kept institutional capital cautious and regulators noncommittal. Wilde’s read of this week’s 52-week topline data from Compass’s Phase 3 COMP005 trial is direct: the question now has its clearest answer yet.
The numbers from Part C of COMP005, covering weeks 26 through 52 in 258 patients with treatment-resistant depression, are worth sitting with. Participants from the 25mg COMP360 arm who received one additional dose showed an average 13-point reduction in MADRS scores from baseline at week 52. Patients who started on placebo and crossed over to receive their first 25mg dose in Part C showed a 10-point average reduction. Across Part C participants, 40 to 45 percent met criteria for clinical response and approximately 30 percent reached remission. No new safety signals emerged. Per Wilde’s post, roughly 70 percent of the 258 enrolled patients continued into Part C, and 80 to 90 percent of those opted for a further dose, which is a retention and preference signal that no daily antidepressant manufacturer could replicate.
The durability objection is functionally dead.
The Infrastructure Gap Nobody Priced In
But answering the science question is not the same as solving the access question, and the field is now staring directly at the latter. Josh Hardman of Psychedelic Alpha framed the challenge this week with unusual bluntness: with potential FDA approval of multiple psychedelic therapies in the coming months and quarters, the field must now translate marketing authorization into patient access. He sketched a dual-track timeline, regulators and government stakeholders on one axis, sponsors and providers on the other, each carrying obligations that the other cannot discharge. The implication is uncomfortable. Compass could receive FDA approval for COMP360 in the first half of 2027, per the company’s stated timeline with a rolling NDA submission and final submission targeted for Q4 2026, and the drug could still be clinically unreachable for the patients it was designed to serve.
Here is the counterintuitive reality that the field keeps sidestepping: psilocybin’s most commercially attractive feature, the fact that patients need only a dose every few months rather than a daily pill, is also its biggest structural liability. A chronic daily medication plugs into existing pharmacy infrastructure, refill behaviors, and PBM contracting logic. A supervised psychedelic session requires a trained therapist, a certified clinical setting, hours of monitored time, and a billing code that most payers have never seen before. The very dosing model that makes psilocybin a “fundamentally different proposition from daily pharmacotherapy,” as Wilde describes it, also makes it invisible to the reimbursement architecture that decides whether patients can actually afford it.
Scheduling is the more immediate constraint. Psilocybin remains a Schedule I substance under federal law. FDA approval does not automatically reschedule a drug; the Drug Enforcement Administration must act, a process that historically runs six to twelve months post-approval and has no hard deadline. MDMA-assisted therapy watched this gap materialize in real time in 2024, when the FDA issued a Complete Response Letter to Lykos Therapeutics citing concerns about trial design and data interpretation, leaving a partially assembled infrastructure, trained therapists, certified sites, and waiting patients, with nowhere to direct. The psilocybin field should not assume its regulatory path will be smoother simply because its data package is stronger.
The Competition Arriving Behind Compass
Tommaso Barba at Imperial College London’s Centre for Psychedelic Research flagged the open-label limitation directly: Part C’s final six months were not blinded, which means the long-term durability results require more cautious interpretation than the Phase 2 double-blind data that preceded them. That caveat matters for the FDA review. The agency will read the COMP005 package against COMP006, Compass’s second Phase 3 trial enrolling 581 patients, which Wilde describes as delivering a more robust confirmatory dataset. But even a clean two-trial package does not resolve the therapist supply problem. Psilocybin-assisted therapy as studied in clinical trials requires specialized training that no medical school currently offers at scale, and there is no accreditation body with the reach to certify the thousands of practitioners a functioning market would require.
Manoj Doss, who this week announced his program’s designation as a Phase 3 clinical trial site for AbbVie’s M26-292 study evaluating bretisilocin for Major Depressive Disorder, represents something worth noting here: this is his team’s fifth psychedelic clinical trial and their fourth industry sponsor. AbbVie, a company with roughly $55 billion in annual revenue, is not running a small speculative bet. It is building Phase 3 infrastructure in MDD with a next-generation compound, which means the competitive window for Compass is narrower than it appears. If Compass launches in H1 2027 into a market still sorting out scheduling, therapist credentialing, and payer contracting, AbbVie’s bretisilocin could arrive into a more functional ecosystem built partly on whatever Compass and regulators figure out first.
That dynamic changes the strategic calculus for Compass in ways that pure clinical success does not capture. Being first to FDA approval in a category that lacks infrastructure is not the same as being first to market in a category that has it. Compass will spend its launch capital simultaneously proving the therapy works at population scale and teaching payers, health systems, and legislators how to accommodate a drug that looks nothing like any psychiatric treatment they have processed before.
What Has to Move Before 2027
The 13-point MADRS reduction at one year is a clinically meaningful number. For context, a 50 percent reduction from baseline MADRS scores is the conventional threshold for “response,” and Compass’s 40 to 45 percent responder rate in an open-label continuation cohort of patients who had already failed at least two antidepressants is a signal that the FDA cannot easily dismiss. The package, combining COMP005 and COMP006 across approximately 840 patients in two Phase 3 trials, is substantive.
But Hardman‘s dual-track framework is the more urgent planning document right now. On the government track: DEA scheduling action must be initiated promptly post-approval, CMS must develop reimbursement pathways that account for session length and therapist time, and state legislatures in large Medicaid markets must act. On the sponsor and provider track: Compass must credential clinic networks before launch, training pipelines for therapists must scale faster than any continuing education infrastructure the mental health field has built before, and payer contracting must begin under conditions of genuine uncertainty about utilization. None of these steps follow automatically from a positive FDA action letter.
The patients in COMP005 waited through at least two antidepressant failures before enrolling. They should not have to wait through a scheduling backlog, a credentialing gap, and a payer education cycle on the other side of approval. Compass’s clinical team answered the scientific question. The answer to the infrastructure question belongs to a much larger, slower, and less motivated set of institutions. That is the race worth watching now.
References
- Lars Christian Wilde, LinkedIn post on COMP005 52-week data and commercial implications, 2025
- Tommaso Barba, LinkedIn post on Compass Pathways 52-week psilocybin results, 2025
- Josh Hardman, Psychedelic Alpha, LinkedIn post on translating psychedelic therapy approval into patient access, 2025
- Manoj Doss, LinkedIn post on Phase 3 site designation for AbbVie M26-292 bretisilocin study in MDD, 2025
Moe Alsumidaie, MBA, MSF, is founder and Chief Editor of Vanguard Publications, which publishes Clinical Trial Vanguard, Pharma Vanguard and BullScope, and Head of Research at CliniBiz. He has two decades in clinical trial operations and data science, with earlier roles at Genentech, Abbott Vascular and Stanford University Medical Center, and is a guest lecturer in clinical trial sciences at Rutgers University.
