Two Phase 3 trials passed, an FDA Priority Voucher granted, and submission of an application for approval announced for the fourth quarter of 2026: COMPASS Pathways has brought COMP360, a standardized psilocybin therapy, through clinical trials for treatment-resistant depression for the first time. This is a historic step because psychiatry has sought alternatives to antidepressants for decades, as these drugs fail to help a significant portion of patients.
When antidepressants no longer work
The WHO estimates that 280 million people worldwide suffer from depression. In roughly 30 percent of cases, antidepressants are not sufficiently effective. After at least two serious treatment attempts, these patients are considered treatment-resistant. Few effective options exist for them. Standard SSRI antidepressants achieve remission rates of 10 to 20 percent in this group.
Until now, esketamine (Spravato, Johnson & Johnson) is the only novel, fast-acting antidepressant on the market, approved by the FDA in 2019. It must be administered repeatedly in certified medical facilities. Electroconvulsive therapy remains the standard for the most severe cases, but carries risks to memory and is heavily stigmatized. The therapeutic gap is substantial.
What the trials show
COMP360 is synthetic psilocybin in a standardized dose of 25 milligrams, administered once under the supervision of trained therapists. Therapeutic effects last six to eight hours. Critically, according to COMPASS Pathways, the environment of the therapy session—the so-called set and setting—is essential to efficacy. A trained therapeutic team prepares patients beforehand and accompanies them during and after the session.
Two separate Phase 3 trials achieved their primary endpoints. In the first trial (COMP005, one dose versus placebo), COMP360 achieved a statistically significant improvement of 3.6 points on the Montgomery-Åsberg Depression Rating Scale compared to placebo (p under 0.001). The clinically meaningful response rate (25 percent reduction on the MADRS scale) after six weeks was roughly 25 percent, with sustained benefit through week 26. The second trial (COMP006, two doses three weeks apart) showed a difference of 3.8 points (p under 0.001). Here, 39 percent of patients achieved clinically meaningful responses.
The effect sizes are statistically robust but moderate. For treatment-resistant patients who have tried multiple medications unsuccessfully, 25 to 30 percent remission from a single session represents measurable progress over existing options. And according to trial data, the benefit persists for at least 26 weeks without patients needing to take daily pills.
Perspective: A historic milestone with open questions
MDMA, another psychedelic, failed FDA approval for PTSD treatment in August 2024. Lykos Therapeutics had worked toward approval for years. The FDA advisory panel cited concerns including blinding problems: patients typically know whether they received a psychedelic or placebo, which can bias self-assessments. Psilocybin shares this fundamental challenge. COMPASS Pathways claims to have built stronger controls against unblinding bias. How the FDA evaluates these measures will determine approval.
Another open question is accessibility. COMP360 treatment requires trained therapists, specialized facilities, and hours-long supervision. This makes it more expensive than a daily antidepressant pill. Whether health insurers will cover the therapy and who realistically will have access remains unclear. The existing esketamine model shows how difficult reimbursement hurdles are for novel psychiatric therapies: in Germany, statutory health insurance only covers Spravato after individual review.
In comparison: Therapies before COMP360
Esketamine (Spravato): The FDA approved an esketamine nasal spray for treatment-resistant depression in 2019. It works rapidly within hours to days but must be administered in clinical settings, initially twice weekly, then less frequently. It is the only novel fast-acting antidepressant to receive approval to date.
Electroconvulsive therapy has been the most effective approach for severe treatment-resistant depression for decades, with remission rates of 60 to 80 percent in select studies. It requires anesthesia, can cause short-term memory impairment, and is heavily stigmatized. It is used far less often globally than clinical evidence would suggest is appropriate.
MDMA for PTSD: The failed approval process by Lykos Therapeutics showed how high the regulatory hurdles are for psychedelic therapies. COMP360 enters this process with two positive Phase 3 trials, a stronger starting position than MDMA had.
Until NDA submission in the fourth quarter of 2026
The FDA granted COMPASS Pathways a Commissioner's National Priority Voucher on April 24, 2026, based on a presidential directive from April 18, 2026. This voucher substantially expedites the regulatory review process. COMPASS plans to submit its New Drug Application in the fourth quarter of 2026. An FDA decision could come in the first half of 2027.
Parallel to this, COMPASS is pursuing submission with the European Medicines Agency, though no specific timeline has been announced. Within the psychiatry community, debate continues about which patients should be eligible: those after failure of at least two antidepressant lines, those with especially severe suffering, or broader access? The FDA's assessment of indication will answer these questions and determine how many people could actually access the therapy.