FDA advisors' scrutiny of MDMA therapy is 'temporary setback,' says Harvard researcher

Some Boston-area researchers said they were surprised by federal advisors' rejection this week of MDMA-assisted therapy as a treatment for post traumatic stress disorder.

The researchers said the decision by advisors to the U.S. Food and Drug Administration reflected challenges facing regulators as psychedelic and psychoactive treatments such as MDMA enter mainstream psychiatry.

On Tuesday, the advisory panel voted 10-1 that recent clinical trials sponsored by Lykos Therapeutics did not produce enough evidence to show the benefits of MDMA, commonly known as ecstasy, in combination with talk therapy, outweighed the risks when treating post-traumatic stress disorder. The panel also voted 9-2 that MDMA is not an effective treatment for PTSD.

Dr. Stephen Haggarty, with Mass General Hospital's Center for the Neuroscience of Psychedelics, called the vote a "temporary setback."

"What's maybe unique about psychedelic drug development is there is a lot of scrutiny — and appropriately so — for how to do this correctly," Haggarty said. "I'm personally grateful for those that are at the forefront, really laying the groundwork for what I anticipate will be other medications that will come.

"To use an appropriate Boston metaphor, I think we're in the first inning," he added.

The FDA advisory panel cited a range of reasons for its concerns, including problems with the data from the clinical trials, as well as the novelty of a request to approve not only a drug treatment but also its use in combination with therapy.

Dr. Mason Marks, a law professor and senior fellow with the Project on Psychedelics Law and Regulation at Harvard Law School's Petrie-Flom Center, joined All Things Considered host Deborah Becker to discuss the panel's decision.

Below are highlights from their broadcast conversation, along with additional comments from the full interview.

On whether the FDA advisory committee during its consideration of MDMA was 'perhaps more rigorous or stringent' than is typical for the panel:

Marks: "The meeting really was extremely thorough and sweeping in its scope. ... I think the level of scrutiny was appropriate.

The FDA panel cited problems with data from the clinical trials in its decision, among other issues. On why what's called 'unblinding' among participants may have prompted concerns: 

Marks: "An 'unblinding' is when participants in a randomized controlled trial can identify which arm of the trial they've been assigned to. And that is a particular concern with psychedelic drugs and other psychoactive substances like MDMA.

"And the reason is that they produce profound changes of thought, perception and emotion. And so it's very obvious not only to the participant, but also to the researchers. So you have unblinding on both sides."

On how much of an issue it was that the FDA was reviewing a combination drug and talk therapy — not just a medication: 

Marks: "Regulating a drug-therapy combination is not something that the agency is accustomed to. It's not necessarily ... a role it wants to be thrust into. And you could almost feel that sense of uneasiness at points in the meeting.

"But another issue is that the committee clearly felt that that therapeutic component of the treatment was not well-defined and perhaps not well standardized."

On whether it was "late in the game" for the FDA to raise questions on the parameters of the clinical trial:

Marks: "The FDA is expected to deliver its decision on this new drug application on Aug. 11 of this year. So you're right that this really is sort of the last step, and we should have a decision very soon.

"... There were recommendations from the FDA that could have changed the direction of those trials. And one thing that seems to have concerned the committee is that the drug sponsor — the manufacturer — may not have been quite as responsive to those suggestions.

"... All parties involved were very sympathetic to the significant unmet need for treatments for post-traumatic stress disorder. ... They just ultimately decided that the data was not sufficient."

On whether the stigma around psychedelics or recreational drugs may have been at play for the FDA advisory committee:

Marks: "Surprisingly, I think stigma played little or no role. The committee and the FDA have expressed great openness to psychedelic treatments — and even enthusiasm for them, [or] cautious optimism. And I feel the same way; I remain very optimistic about psychedelic treatments."

On how much of a setback Dr. Marks thinks the FDA advisors' votes may be: 

Marks: "I agree that this is a temporary setback. I'm moved by the reports of people who benefit from MDMA, and there is a risk that if the application is denied, it could delay the availability of MDMA to people who could stand to benefit. And it's unclear what the FDA will do when it renders this decision in August.

"There certainly have been cases where the agency has gone against the advice of its advisory committees, but that doesn't usually happen.

"There is such enthusiasm, and there is that unmet need for psychedelics — and there are many other companies in this space with treatments in the pipeline — that I don't think it will significantly negatively impact the sector on the whole if the application is rejected."

Correction: The FDA panel voted 9-2 that MDMA combined with talk therapy is not an effective treatment for PTSD. It voted 10-1 that the risks of MDMA do not outweigh its potential benefits.