Rick Doblin, the founder of the Multidisciplinary Association for Psychedelic Studies, which founded Lykos, bemoaned a “moving of the goal posts” in Lykos’ rejection but looked for positives in the newly released complete response letter.
Lykos Therapeutics founder Rick Doblin has something to say now that the public can see the FDA letter that shot down the company’s midomafetamine (MDMA)-assisted therapy for post-traumatic stress disorder in August 2024.
The FDA’s rejection of Lykos’ drug at the time did not come as a shock. The complete response letter (CRL) arrived after an advisory committee meeting voted 10-1 against recommending approval.
But now, after the FDA released another cache of rejection letters, the agency’s specific objections have been entered into the public domain. For Lykos, which re-branded itself last week as Resilient Therapeutics, those concerns include unreported safety events at two different sites, as well as abuse of the drugs, their duration of effect, study design and the number of patients who had previously reported using MDMA.
For example, in the CRL to Lykos, the FDA said that the company had not demonstrated that the drug’s effect was durable past an 18 week end-of-study assessment, which came eight weeks after the last dose of the drug.
“Now that the CRL is public I’ve got some comments about it,” Doblin said during a Friday press conference to discuss the public release of Lykos’ CRL. “There is a changing of the goal posts.”
Doblin—who also founded Multidisciplinary Association for Psychedelic Studies (MAPS), the organization that initially founded Lykos—went on to detail a long history of Lykos and midomafetamine’s development history. In particular, he noted that between the time the advisory committee nearly unanimously voted to not recommend Lykos’ drug and the actual decision by the FDA to reject the drug, Lykos submitted an amendment to the new drug application for the therapy addressing the agency’s concerns.
Doblin quoted the newly released CRL directly: “We also acknowledge the receipt of your amendment dated, and then the date is blocked out, which was not reviewed for this action.”
The amendment was submitted by Lykos, according to Doblin, to address many of the issues raised by the advisory committee, which focused on efficacy and durability of response demonstrated in Lykos’ data, before the FDA rendered its decision.
“Those responses from the company were not considered in this complete response letter,” Doblin said.
Meanwhile, durability of response has never been a condition of FDA approval, Doblin contended, pointing to the durability of many cancer drugs, where relapses after treatment may be common. He also pointed to Johnson & Johnson’s esketamine therapeutic Spravato, approved for major depressive disorder and treatment-resistant depression.
“Results fade pretty quickly with Spravato,” Doblin said. The therapy was approved based partially on data showing duration of response through at least 32 weeks.
Doblin also addressed part of the FDA’s CRL that recommended a new randomized, double-blind study to address durability of effect.
“The issue of how to do a double-blind study is very complicated,” Doblin said, stating that discussions of how to conduct such a trial delayed Lykos’ moving to Phase III by eight months. Part of the issue, according to Doblin, is that it’s difficult to blind a study for a drug that has at least a partially psychedelic effect on participants.
“The FDA said that often in practice, the double blind fails to work anyway, even with SSRIs,” where significant side effects can tip a patient off on whether they received an active ingredient or a placebo, Doblin said. He also pointed out that Spravato was approved based only on single-blind studies.
Doblin said that MAPS is talking directly to the Trump administration but did not provide details. “MAPS is now engaged in discussions with people in the administration, not in the FDA, about whether we already have an evidence-based therapy,” citing 25 years of what he called “interdirected therapies,” without specifying what those were or what those discussions entailed.
At the end of the day, however, Doblin sees a light at the end of the tunnel for psychedelic therapies. “I am so relieved that the FDA released this CRL,” he said. “The for-profit psychedelic industry has got the wrong message.” According to Doblin, the message received by psychedelic drug companies is that psychotherapy is a problem and that they should try to minimize the role of it in mental health, instead focusing on therapeutics.
“‘Don’t do any therapy. Try to be just drug companies,’” Doblin described of the erroneous message. Instead, he insisted, “the field should get the idea that it’s about what’s best for patients.”
