How likely is it that Lykos Therapeutics’s MDMA therapy will get FDA approval?

In a high-profile decision, an FDA advisory committee voted 9–2 in early June against recommending approval for Lykos Therapeutics’s MDMA-based therapy, citing a lack of evidence to prove it works and is safe.

The drug, designed to treat post-traumatic stress disorder (PTSD), would be the first FDA-approved psychedelic therapy. It would also be the first new treatment for PTSD to receive approval in more than two decades.

An advisory committee’s recommendation is non-binding, so the drug still has a shot. The agency is set to make its final decision on August 11, leaving the public to wonder: How likely is it that Lykos’s MDMA therapy will get a nod from the FDA?

Historically, the agency tends to agree with the advisors’ recommendations. A 2019 study from New York University School of Medicine and Yale found that the FDA aligns with committee consensus about 80% of the time. Out of 376 voting meetings between 2008 and 2015, the FDA went against advisory committee recommendations 83 times, the study found.

But there have been some instances when the FDA green-lit a drug without endorsement from an advisory committee. In June 2021, for example, the agency approved Biogen’s Alzheimer’s drug Aduhelm after a panel rejected the application, citing concerns over a lack of evidence that the medicine works.

Amy Emerson, CEO of Lykos Therapeutics, told Healthcare Brew that she can’t give an estimate on the likelihood of the drug getting the green light, but she is confident “the FDA will continue to follow and evaluate the data.”

Emerson said Lykos was expecting a “mixed vote” in June, but the California-based drug company was taken aback at “the level of stigma that was still present.”

“We were really disappointed in that part, but not necessarily surprised, because we knew that we’re advancing a really novel treatment,” Emerson said. “The [advisory committee] is supposed to be a group of independent, external experts, but they also have to be completely unconflicted, so it’s hard to have a group of completely unconflicted experts on something new and novel.”

The committee didn’t have “all of that context and understanding” of the work Lykos has done with the FDA “over the course of a lot of years,” she added. “The FDA has had time to wrap their head around and understand the data. [The agency has] worked with us on the study design, so they have a lot of knowledge about it that would be difficult for a group of people to come in and fully understand something that’s this complex in a short period of time and then be independent experts on it.”

Does the ‘no’ vote spell trouble for other psychedelic medicine developers?

A number of other pharmaceutical companies are working to develop psychedelic medicines, including MindMed, a clinical stage biopharma company developing an LSD-based medicine to treat generalized anxiety disorder, and Compass Pathways, which is working on a psilocybin-based therapy for treatment-resistant depression, PTSD, and anorexia nervosa.

Daniel Karlin, chief medical officer at MindMed, told Healthcare Brew that the vote was actually “very educational.”

“We’ve been doing our development program in a very different way than Lykos,” Karlin said. “Many of the objections, if not all of the objections, that were raised by the [committee] are things that we’ve thought about taking steps to ameliorate, and I think that we have better answers and a better ability to bring forward data that will be familiar, recognizable, and not raise many of the risks that were raised in that outcome.”

Chris Williams, chief communications officer at Compass Pathways, said the committee’s vote “was an important step in the journey to bring better options to patients.”“The discussion highlighted important issues for consideration, especially regarding patient safety,” Williams wrote in an emailed statement to Healthcare Brew. “Compass Pathways has designed its clinical programs to include robust monitoring of a broad range of safety risks and the standardization of psychological support and pre- and post-administration follow-up.”

Lykos’s path forward

The negative response from the advisory committee “makes things a little bit harder” for Lykos, according to Emerson.

“But, we keep going,” she said. “We have to still do all the same things now that we were planning to do before the [vote]. We still have a number of interactions with the FDA that are planned and all of that continues.”

Moving forward, Emerson said Lykos will take the advisors’ apprehensions into consideration.

“We’ve heard the concerns, and I think they’re all manageable with a proper risk evaluation mitigation strategy,” she said.

If the FDA ultimately votes against approving the MDMA therapy, Emerson said that won’t stop Lykos from continuing its research and development.

“I can’t imagine that August 11 is some kind of date where we just stop working,” she said. “I think that it’s more likely to be a date where, if it’s not approved, a lot of information is obtained about what is still necessary and that we would keep working on it. There’s too much need out there and too much work has gone into this—and there’s too much evidence available from these studies that there is effectiveness and safety of MDMA-assisted therapy, and so we will keep working.”