The agency’s finalized recommendations for clinical testing of psychedelic compounds for mental health could pave the way for companies like Compass Pathways, whose psilocybin-based therapy for treatment-resistant depression could win approval as early as this year.
The FDA released final guidance Monday for developers of psychedelic drugs, an update of its draft recommendations from 2023 that provides an initial framework for future regulatory action.
“FDA’s final guidance on psychedelics suggests the agency remains receptive to helping sponsors succeed,” Jefferies said in a note to investors on Monday.
The announcement comes on the heels of positive data from Compass Pathways and Definium Therapeutics, both frontrunners in the psychedelics space. The final version of the guidance also follows President Donald Trump’s executive order earlier this year urging U.S. health agencies to allow an established path to approval for drugs such as psilocybin, MDMA and even ibogaine.
Much of the feedback the FDA received from stakeholders following the draft release concerned clinical trial design, particularly around distinguishing the therapeutic mechanism of the drug candidate from other factors that might come with the psychedelic effects.
Not much has changed from the draft version three years ago. But the latest iteration, released Monday, grants more flexibility for sponsors bringing psychedelic compounds to the agency’s doorstep, both in terms of modeling abuse potential and measuring overall effectiveness.
The guidance states that abuse potential studies may not be necessary when an assessment has already been “well-characterized from extensive clinical studies and robust epidemiological data exist,” adding that sponsors should reach out to the FDA if they “believe there is sufficient existing data that the human abuse potential is already well-characterized.”
Placebo trials of psychedelic drugs are complicated by the noticeable effects of the drugs on the patient, particularly those who have taken them before. The guidance suggests additional blinding mechanisms and durability tests to help ensure reliable data.
The final guidance “largely reaffirm[s] the existing framework while signaling a preference for blinded durability data,” H.C. Wainwright said in a Tuesday note to investors.
The guidance also sets the bar for a clinical hold in cases that include risk of illness or injury, including supervision by a trained healthcare provider following administration.
Companies like Compass and Definium, among others, stand to benefit from the guidance. Compass is developing a psilocybin-based therapy, COMP360, for treatment-resistant depression, for which it received an expedited Commissioner’s National Priority Voucher review in April following Trump’s executive order. Last week, new data from a Phase 3 trial of treatment-resistant depression showed that the treatment worked quickly and durably, further supporting an ongoing rolling submission for COMP360.
Definium’s formulation of LSD, meanwhile, showed “profound” efficacy in a late-stage trial last month, results that Definium CEO Rob Barrow said “bring us one step closer to potentially delivering a transformative new treatment option as we advance toward FDA submission.”
The FDA will hold a public hearing regarding therapeutic use of psychedelic drugs on Sept. 14. Jefferies called the timing and “exact intention” behind the meeting “curious,” wondering if it “obviates the need for pot’l future AdComs unless the clinical data are controversial”—particularly as COMP360 could be approved by the end of this year.
The final guidance could also be particularly apt as Health Secretary Robert F. Kennedy moves forward with his initiative to get Americans to stop taking another class of psychiatric drugs, selective serotonin reuptake inhibitors (SSRIs). Earlier this month, mental health professionals met with federal health officials to discuss clinical guidance they hope will lead to deprescribing of SSRIs, STAT News reported on Monday.
The Trump administration’s push for psychedelic therapy approval has been a mixed bag in scientific circles, generating public buzz for much needed novel mental health treatments while also setting off alarms that the benefits are exaggerated.
“Ultimately,” Jefferies said, “a friendlier regulatory environment should make psychedelics a more investable space.”
