With a new batch of favorable phase 3 results under its belt, Compass Pathways is setting its sights on an FDA approval for a psilocybin-based drug. But whether COMP360 will win the first nod for a “classic” psychedelic remains to be seen amid signs of internal discord at HHS.
Health Secretary Robert F. Kennedy Jr. and FDA head Dr. Marty Makary have made public statements signaling enthusiasm for psychedelic options, but there are also signs of reticence among other regulatory officials, who may take a more conservative view of the drug class.
In October, the psilocybin therapy, which has been in late-stage trials for treatment-resistent depression, was abruptly removed from the list of sponsors chosen for a new voucher program just before it was announced, according to Stat News. The selection would have accelerated the standard 10-to-12-month FDA review timeline.
Compass said it now plans to submit the new drug application for COMP360 between October and December. If the FDA does sign off on the drug, it could offer a new option for patients with limited treatment options.
“Treatment-resistant depression is a real challenge for the field and there's an urgent need for accessible treatment options that work quickly, safely and effectively,” the National Alliance for Mental Illness’ Chief Medical Officer Dr. Ken Duckworth said in an email. But several questions still need to be answered.
“This phase 3 trial marks a novel approach and a hopeful step forward, but there is a lot more to learn about how the treatment works, who it works for, and how it would be used relative to other interventions for treatment-resistant depression like esketamine and transcranial magnetic stimulation,” Duckworth added.
Positive momentum
The COMP360 phase 3 results announced this month showed the drug reduced symptom severity while producing mostly mild to moderate side effects. Approximately 39% of patients treated with the drug experienced a 25% or more improvement in symptoms on a standardized scale, and it continued to work over 26 weeks in patients given one or two doses.
“This is a remarkable achievement for the field of psychiatry, especially in the treatment-resistant population, where proving benefit has historically been extraordinarily challenging,” Kabir Nath, Compass’ CEO, said in a written release.
Compass’ results have been highly anticipated in a field that’s faced numerous setbacks.
Compass initially delayed reporting the results of an earlier phase 3 trial due to issues related to trial blinding, triggering a round of layoffs. While the results of that trial, released in June, ultimately showed that it met its primary endpoint, some investors were underwhelmed by the results.
Like other psychedelic drug developers, Compass has had to overcome numerous trial-related challenges due to the nature of the treatment. Among the biggest hurdles was maintaining blinding while testing a drug that produces apparent dissociative effects. The more recent phase 3 Compass trial used a lower dose of the psychedelic as a control instead of the placebo used in its earlier phase 3.
Other psychedelic companies have run into trouble, including Lykos Therapeutics, which experienced a high-profile failure in 2024 when the FDA rejected its MDMA drug for PTSD, citing concerns over trial design.
Pharma’s growing psychedelic interest
These setbacks haven’t derailed interest in the field, which has also seen success stories, including Johnson & Johnson’s esketamine-based depression treatment Spravato. While not considered a classic psychedelic, the ketamine-derived drug got off to a slow start but has since achieved blockbuster status and continues to climb.
To get in on the rising market, AbbVie recently spent $1.2 billion on a psychedelic depression candidate, bretisilocin, which it acquired from Gilgamesh Pharmaceuticals. The deal shows growing interest in the space despite the challenges.
Other companies bringing psychedelics to market include GH Research and Cybin.
While Kennedy told Congress last summer that this “line of therapeutics has tremendous advantage if given in a clinical setting,” and that he’d like to see a psychedelic approval within a year, there’s concern among experts in the field that moving too fast could undermine confidence in this potential new drug category.
In the coming months, Compass’s regulatory journey may be a test case for how these drugs could fare under FDA scrutiny
