Johnson & Johnson’s landmark approval for Spravato in 2019 busted the door open for a new era of mental health drugs. The esketamine-based depression treatment not only helped validate psychedelics in the psychiatric realm, it’s shown the therapies can reach blockbuster heights as well.
Now, with a path cleared on the market and the FDA signaling its willingness to embrace psychedelics, the next wins could be around the corner.
Compass Pathways is heading toward an FDA submission for its psilocybin-based depression treatment after positive phase 3 results. And Definium Therapeutics isn’t far behind with its lead program based on LSD.
Definium is currently conducting two late-stage studies in generalized anxiety disorder with its lead candidate DT120. Building on momentum from its positive phase 2 data, including one study that demonstrated a 78% clinical response rate and 50% remission after four weeks, the company expects topline phase 3 results in the coming months, potentially teeing up an approval by next year.
If it succeeds, Definium, formerly MindMed, will be making its mark on a treatment landscape for anxiety that’s been at a standstill since the FDA approved Eli Lilly’s Cymbalta in 2007.
The anxiety space is also in need of innovation. About 50% of GAD patients in the U.S. “respond inadequately” to the approved anti-depressants and many “do not experience sustained relief,” according to a study by Definium.
The goal is to not just deliver something new, but a drug that’s “best in class,” according to the company’s CEO, Robert Barrow.
Although the science around why LSD improves anxiety remains fuzzy, mechanistic theory suggests it could be linked to a receptor called 5-HT2A and that its sustained effect is tied to its neuroplasticity in multiple regions of the brain.
“We’re driving change on a different level,” Barrow said. “It’s not just symptom suppression. It’s a reorientation of the trajectory of the condition.”
As Definium looks ahead to a potential rollout, it’s preparing to step onto a stage well built for its arrival.
The path to launch
Like J&J’s Spravato and Compass’ depression treatment, DT120 produces a psychedelic effect and has to be administered under trained clinical care. About five hours after receiving a dose, patients start undergoing assessments before being released from the clinic, Barrow said.
While this adds complexity to administering the treatment, patients mostly just need a “relatively comfortable room where they can sit down for a while,” Barrow said. The growing number of clinics that already administer Spravato could be a boon if Definium’s drug hits the market.
“There are about 7,000 centers that can deliver Spravato,” Barrow said. “We have yet to find one that can’t [also] deliver DT120.”
The unique conditions needed for providing Spravato haven’t thwarted its skyrocketing sales. Despite getting off to a sluggish start during the pandemic, sales for the treatment have since ballooned, growing 57% last year and crossing the blockbuster threshold.
Definium also has a large market in sight. While the company is not yet guiding on the sales potential of DT120 for anxiety, the latest data suggests that the condition impacts about 10% of the U.S. population, Barrow said.
The company could also one day go head-to-head against Spravato in the depression market as well. In addition to testing DT120 in anxiety, the candidate is in a phase 3 study for major depression disorder, with a readout expected by the end of the year.
Autism, one of the most vexing conditions in neuroscience drug development, is also being targeted for psychedelic research. Several groups of scientists are probing the effects of psychedelic compounds on autism, including Definium, which launched a phase 2 trial of an MDMA-based candidate last year.
For now, Definium is working closely with the FDA on trial design to help ensure it doesn’t fall victim to the challenges that triggered the high-profile failure of Lykos Therapeutics’ MDMA drug for PTSD, which was rebuffed by the agency amid recreational abuse concerns and a lack of sufficient data.
“Our general approach is to put our heads down and treat this like we’re developing any other drug,” Barrow said.
