From its headquarters in the heart of New York City, Definium Therapeutics has dropped topline phase 3 data for its psychedelic answer to depression that is almost certain to keep the field’s hype train rolling.
The biotech’s LSD recipe, known as DT120 ODT, scored wins on all primary and key secondary endpoints of the 149-patient Emerge trial, Definium announced Monday, June 22, marking a reduction in depression symptoms not hit by competing medicines.
“If ‘pretty good’ encompasses the best data ever seen in a pivotal study of depression, I think we would say pretty good,” Definium CEO Robert Barrow told Fierce Biotech in an interview ahead of the trial's official reveal.
“It's really of a magnitude, of a rapidity, and of a durability that we've never before seen in a phase 3 study,” Barrow added. Definium was formerly known as Mind Medicine or MindMed before rebranding in January.
The market agreed with the CEO's positive framing, sending its shares up more than 30% in premarket trading shortly after the data were made public.
In a presentation provided to Fierce in advance of the data readout, Definium noted that DT120’s 8.1-point placebo-adjusted reduction of symptom severity on the Montgomery-Åsberg Depression Rating Scale (MADRS) was higher than those seen in similar trials for both existing medicines, like Takeda’s Trintellix and Axsome Therapeutics’ Auvelity, and an investigational psilocybin rival from Compass Pathways.
The second-highest mark of a 6.8-point reduction came from Johnson & Johnson’s ketamine-based nasal spray Spravato. While directly comparing these trials isn’t possible due to differences in methodology and patient populations, Definium’s presentation calls DT120’s profile best-in-class.
DT120 posted solid safety results, Definium said in the release, with no new safety signals and no signs of increased suicidal ideation or behavior.
“These results stand apart from existing treatments, representing a potentially new paradigm for the management of major depression," John Sonnenberg, Ph.D., the trial’s principal investigator and a clinical psychologist at Uptown Research Institute and Northwestern University Feinberg School of Medicine, said in the release.
The trial’s primary endpoint, change in MADRS score from baseline, was assessed six weeks after dosing. At 12 weeks the average MADRS score reduction was 7.1, notching a win on a secondary endpoint. A 40-week open-label extension arm is currently ongoing.
“When we see a response, we see a really dramatic and rapid response,” Barrow explained. The extension phase is meant to test how patients who aren’t helped by the first dose may respond to subsequent experiences with DT120. Ultimately, the CEO said, how many times a potentially approved version of the drug is given will depend on an individual patient’s needs.
In the trial, patients were given either 100µg of DT120 or placebo and then monitored by an attendant who chaperoned them through the eight-hour session.
“Their perceptual fields vary, their thought processes can become very intense, they can become emotional, and we serve as a grounding force for them,” Sonnenberg told Fierce in an interview ahead of the readout.
This “grounding force” is purposefully different from the psychedelic-assisted psychotherapy approach taken by rival Compass, Daniel Karlin, M.D., Definium’s chief medical officer, told Fierce in a joint interview with Sonnenberg.
“What we provide in the room is meant to support people through the session, but it's not meant to be any sort of an intervention that contributes to the outcome for the patient,” Karlin said.
Another factor separating Definium from its competition is its choice of psychoactive drug, Karlin said.
“We have every reason to think that LSD specifically is the best drug in the category,” the exec explained, being both “remarkably potent” and “uniquely gentle” when exerting its effects.
The drug was also the first psychedelic to be seriously studied as a potential medicine, Karlin noted, after Swiss chemist Albert Hoffman, Ph.D., discovered its hallucinogenic effects first-hand in 1943.
Definium is also pitting DT120 against generalized anxiety disorder in two phase 3 trials, alongside a lower-dose phase 3 study in depression. Readouts from these trials are expected later this year, and Barrow said Definium is waiting to have more data in hand before discussing with the FDA on the best path forward for approval.
Following precedent in psychiatry, approval would likely first focus on patients whose depression has not responded to two prior antidepressants, Barrow added.
“For every new entrant in psychiatry, there's a requirement of having tried two prior drugs, and that requirement is put in place so that patients can get approval for the drugs to be paid for,” he said. “I think that's a reasonable expectation here.”
Psychedelic hype hit a new zenith in April, when u.s. President Donald Trump signed an executive order instructing the FDA to grant priority review vouchers to companies working in the space. Compass was chosen for a voucher, along with the Usona Institute—where Barrow previously worked—and Transcend Therapeutics. Definium was not granted a voucher.
“We certainly believe there's a lot of momentum behind us and the field more broadly,” Barrow said. The company has moved quickly over the past five years to launch its suite of phase 3 studies for DT120, he said, but not all fast tracks are created equal.
“We're always looking for opportunities to accelerate things, but we want to make sure that the process by which we accelerate them doesn't introduce risk,” the chief exec said.
While agreeing with Barrow that support for psychedelics from the executive branch is generally a good thing, Karlin put the potential risks a bit more bluntly. Given that the Trump admin’s backing of psychedelics was spurred by the podcaster Joe Rogan and has triggered widespread concerns of potential political influence in the FDA’s operations, it may be best that Definium’s path to approval circumvents the priority voucher quagmire.
“What we don't want is an approval that has a political flavor to it,” Karlin said. “The last thing we'd want is for anybody to think that we got shortcuts or that our review and approval was unscientific in some way.”