FDA Grants DT120 Second Breakthrough Designation, Now for MDD
Key Takeaways for Clinical Practice
- On September 8, 2026, the US Food and Drug Administration (FDA) granted psychedelic therapy DT120 Breakthrough Therapy designation for major depressive disorder (MDD), following its August 2026 designation for generalized anxiety disorder (GAD).
- The phase 3 Emerge randomized, double-blind, placebo-controlled trial compared a single 100-µg DT120 dose with placebo in 149 patients with confirmed MDD across 20 US sites.
- Company-reported topline findings showed placebo-adjusted Montgomery-Åsberg Depression Rating Scale changes of −8.1 points at Week 6 and −7.3 points at Week 12 (both p < .0001), with mild-to-moderate transient adverse events; the ongoing Ascend trial includes a low-dose arm to strengthen masking.
The US FDA has granted Breakthrough Therapy designation to DT120, lysergide in the form of an oral disintegrating tablet (ODT) developed by Definium Therapeutics, for the treatment of MDD.
The designation is supported by evidence of “significant unmet medical need” in the MDD care landscape as well as results from the phase 3 Emerge study conducted by the company. An estimated 21 million adults in the US experience a major depressive episode each year, according to the National Institute of Mental Health.
The FDA decision marks the second Breakthrough Therapy designation for DT120 ODT. The first was granted in August 2026 for GAD.
"Securing our second Breakthrough Therapy designation underscores the potential of DT120 to meaningfully transform the treatment landscape for people living with serious mental health disorders," said Rob Barrow, Chief Executive Officer, Definium Therapeutics. "This recognition of DT120’s promise, first in GAD and now in MDD, reinforces the urgency to advance and deliver rapid, durable benefit across multiple indications.”
Phase 3 Emerge Trial Supports Breakthrough Therapy Designation
The phase 3 multicenter, randomized, double-blind, placebo-controlled Emerge trial included 149 patients across 20 US sites who had a confirmed MDD diagnosis. Patients were randomized to receive a single 100 µg dose of DT120 or placebo.
Final analysis showed an -8.1-point placebo-adjusted change in Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline at Week 6 ( p < 0.0001) and a -7.3-placebo-adjusted change in MADRS at Week 12 ( p < 0.0001).
According to the company’s topline findings, the antidepressant effect was rapid and sustained through Week 12, and DT120 was generally well tolerated.
Treatment-emergent adverse effects ranged from mild to moderate in severity and were described as “transient.” No increase in suicidal ideation or behavior was observed. Discontinuation rates were low.
The ongoing phase 3 Ascend study is continuing evaluation of DT120 for MDD by including a low-dose arm designed to strengthen masking by making it more difficult for participants to determine their assigned dose.
Further Applications Under Investigation
Additional development of DT120 is underway for use in GAD, posttraumatic stress disorder (PTSD), and potential application in other serious brain health disorders. Last month, Definium announced positive topline data in the phase 3 Voyage study of DT120 for GAD.
The randomized, double-blind, placebo-controlled trial met its primary endpoint and all key secondary endpoints. Participants exhibited a placebo-controlled change of -5.4 points from baseline at Week 12 in the Hamilton Anxiety Rating Scale (HAM-A) ( p < 0.0001). The onset of effect was rapid, sustained, and well tolerated, with no new safety signals identified.
“With no new medications approved for GAD in nearly two decades, Definium is validating a non-daily treatment paradigm that could establish a new and long-overdue standard of care for the more than 50 million adults in the US suffering from anxiety and depression,” the company said in a press release.
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