FDA Signals Shift to Single Phase 3 Trials for Drug Approvals, Opening Door for Faster Psychedelic Therapies

LOS ANGELES – The Food and Drug Administration is preparing to overhaul its evidence requirements for new drug approvals, making a single well-designed Phase 3 trial the standard rather than the exception. This adjustment, outlined by agency Commissioner Marty Makary, could streamline paths to market for therapies in mental health, including experimental psychedelic treatments for post-traumatic stress disorder (PTSD), depression, and anxiety.

Makary emphasized the scientific foundation for the change. “You can achieve the same statistical power with one trial as you would with two trials when it’s designed and controlled appropriately,” he said. The policy update, expected within three to six months, builds on existing flexibility. In 2024, 66% of novel drug approvals relied on one pivotal study, often supplemented by prior data. Historically, the FDA has demanded two trials to confirm safety and efficacy, but exceptions have grown common for urgent needs like rare diseases or oncology.

The move arrives amid internal shifts at the agency, including the abrupt retirement of veteran regulator Richard Pazdur, who oversaw oncology approvals. Some experts question whether easing standards risks overlooking subtle risks in complex areas like psychiatry, where outcomes often hinge on patient reports. “This is really starting to feel like taking a flamethrower to regulatory standards for no reason,” said STAT News editor Matthew Herper, pointing to cases where replication uncovers flaws.

Legislative tailwinds add urgency. On December 4, a cross-party group tabled the Freedom to Heal Act, tweaking the Controlled Substances Act to permit “right to try” protocols for Schedule I psychedelics like MDMA and psilocybin in dire, refractory cases qualifying as FDA breakthroughs. The measure would task the DEA with approving doctor-led delivery when conventional care falters, addressing a void in expanded access for acute mental health threats.

If implemented with rigorous trial controls, the policy could deliver real progress for patients, including terminal ones, waiting on life-saving advancements. But any slippage in oversight might invite setbacks, reminding developers that speed without substance solves nothing. The next six months will reveal whether this reset truly balances innovation with accountability.