According to STAT, FDA is set to modify its policies to reflect a new expectation: just one pivotal trial will be sufficient for new drug applications (NDA), not two. While two studies may be required in some cases, it would become the exception, not the rule. The agency has yet to formally announce the change.

Commissioner Marty Makary told the outlet that the agency “will also start updating policies to reflect the change, which could take three to six months.” The change will only become the new normal, STAT understands, once guidance is updated.

While Makary and co. are branding the move as part of a larger agenda of cutting what they deem to be unnecessary bureaucracy that slows the approval of new drugs, the majority of new molecular entity (NME) approvals are already approved on the basis of one pivotal trial. (And it’s been that way since 2020.)

Last year, in fact, 66% of NME approvals were handed down after just one pivotal trial had been submitted to the agency. Draft guidance from 2023 also lays out how sponsors can demonstrate efficacy with one pivotal study plus confirmatory evidence (PDF).

The vast majority of these single-pivotal-trial NME approvals are in areas like oncology and cardiology, though. Just one psychiatric NME was approved in 2024, Cobenfy for schizophrenia in adults. That package included two Phase 3 studies, which had identical designs and a collective N of 470.

So, while single-Phase-3 approvals might be standard in other disease areas, they’re not common in psychiatry… and they may be controversial.

Already, some have argued that the agency is lowering its standard unnecessarily, given that it can (and often does) make concessions to its two-Phase-3 default expectation in cases where patient access would be drastically delayed or where it is otherwise impractical.

Some of these critics suggest the move is part of an overall lowering of standards across the agency. “This is really starting to feel like taking a flamethrower to regulatory standards for no reason, STAT’s Matthew Herper wrote on X. He added that there are often good reasons to insist on two studies, “especially for, say, psychiatric drugs.”

Indeed, drug development in psychiatry is mired with additional considerations and obstacles, as psychedelic developers are all too aware. Those include a reliance on subjective endpoints, which, among other things, have led to replication challenges.

That might be why the Division of Psychiatry has not commonly conferred things like rolling review, until recently, or encouraged single-pivotal-trial submissions.

Some psychedelic drug developers will likely welcome the news, which came just one day after we highlighted the fact that Usona Institute could seek approval of its psilocybin candidate on the basis of its single, 240–patient Phase 3 study.

If FDA does roll out a one-pivotal-trial policy across the board, it will surely bring drugs to market faster, but it’s not clear how healthcare payors or providers might view those products. They may, for example, retain concerns around the quality or replicability of the data. Additionally, drug developers with aspirations of also launching outside the U.S. will have to consider other jurisdictions’ currently unchanged regulatory requirements.

It’s interesting to begin to think about how this could play out in the case of psilocybin, though there are still too many unknowns to begin modelling with any surety. If Compass’ psilocybin product secures approval, its two-study Phase 3 program representing more than 800 patients and two different trial designs should instil some level of confidence in payors and providers.

But what if Usona is able to bring another psilocybin product to market shortly after? While its single Phase 3 study was much smaller, providers and payors might view its product as substantially similar to Compass’, and thus derisked. In that sense, then, it could piggyback on Compass’ commercialisation efforts, particularly prescriber education (despite Compass’ presumed efforts to set its COMP360 apart). A lot might hinge, then, on whether FDA deems Usona’s psilocybin an NME, as well as where others like the USPTO stand.

To emphasise: there are many unknowns. But, one thing is sure: Usona’s progress will be watched more closely than ever by Compass, as well as observers like Psychedelic Alpha.

It will also be interesting to follow which psychedelic drug developers pursue single-trial Phase 3 programs more generally.

Regular readers will recall that AtaiBeckley executives have made varying statements around whether they expect to commence a one- or two-trial Phase 3 program.

The company’s Chief Research & Development Officer, Rob Conley, told us in the summer that FDA could say it only needs one more study for approval. But speaking to Psychedelic Alpha last month, AtaiBeckley CEO Srini Rao said that one study is unlikely to be large enough to generate a sufficient safety database for the agency.

If the agency is genuinely changing its expectations, though, might the company’s funders, including Christian Angermayer, who graced the MAHA Summit stage in D.C. last month, insist that it guns for a single-study Phase 3 program, which could…