MDMA drug developers set new priorities after Lykos rejection for PTSD

MDMA drug developers set new priorities after Lykos rejection for PTSD

Once confined to the party scene, midomafetamine, or MDMA (colloquially known as ecstasy), has recently gained attention for its therapeutic potential. The Schedule I drug has proven to be special promise in the treatment of post-traumatic stress disorder (PTSD), a serious mental illness with known few treatment options.

However, the field of psychedelic treatment suffered a setback when the FDA rejected Lykos Therapeutics' MDMA-assisted therapy for PTSD in August. In its full response letter, the agency said the application “could not be approved based on the data submitted to date” and asked Lykos to conduct an additional Phase III study to obtain more information about the drug's safety and effectiveness .

The Feeling It appears that the FDA's problems reflected Lykos' new drug application (NDA) rather than MDMA as a whole.

“I think the setback that Lykos has suffered is mainly reflected in Lykos.” [trial design] and not so much on MDMA,” said Matthew Baggott, co-founder and CEO of psychedelic specialist Tactogen BioSpaceand added that in addition to the data deficiencies, there may have been “extra-scientific” factors, including political pressure.

Still, some psychedelic drug developers are reassessing their pipelines and prioritizing other assets. They are taking a wait-and-see approach to MDMA while working to make the drugs safer.

Tactogen, for example, is reviewing its strategy.

“The fact that Lykos has not received NDA approval this cycle means we are seriously considering prioritizing our novel compounds and waiting to move forward with our MDMA product,” Baggott said. Tactogen's pipeline includes a number of preclinical molecules that Baggott believes will be superior to MDMA.

Psychedelic medicine colleague Atai Life Sciences is prioritizing its MDMA-based compound EMP-01 for social anxiety disorder. initiate a Phase II trial in late 2024. For PTSD, the company will “see how it works out with Lykos,” said co-CEO Srinivas Rao BioSpace.

The Lykos decision is “good overall for companies like Tactogen as we continue to have a clearer and clearer roadmap from the FDA about what they want,” Baggott said, pointing to the FDA's recent guidance, Lykos' Adcomm documents and the public statements following that meeting.

The FDA has issued one Instructions June 2023 document for psychedelic drug trials, recognizing that these compounds present unique challenges for study design. Safety concerns cited include potential for abuse and changes in consciousness and behavior that can last for several hours.

Baggott said the biggest challenge to approving MDMA is the concept of abuse liability. Therapeutic outcomes such as feelings of self-compassion or emotional positivity are considered warning signs of possible abuse, he said. Some of these effects can be “easily mapped” using the Medical Dictionary of Regulatory Activities (MedDRA), Baggott added, but other experiences patients might have while taking MDMA are more difficult to map to standardized medical terminology. It will be “really important” to record these events in a way acceptable to the FDA.

Other experts have argued that MDMA is not commonly abused in recreational settings. Howard Kornfeld, a medical director at Recovery Without Walls who worked with patients treated with MDMA in the 1980s before it was a scheduled drug, said it is rarely abused. He clarified that in “unusual situations” MDMA can be taken in the wrong dosage, which can lead to poor results.

The Lykos regimen requires patients to undergo three sessions under full supervision, Kornfeld noted. “People don’t get addicted from these three sessions,” he said, adding that despite fears that patients might “get a taste” of the drug and seek it out on the streets, “we really haven’t for 40 years.” “Years of real data.”

Read the full article on BioSpace.