A single dose of DT120 lysergide (LSD) orally disintegrating tablets (ODT) provided rapid and durable antidepressant effects in adults with major depressive disorder (MDD), with no serious safety concerns identified, topline results from a phase 3 trial show. 

The Emerge study met its primary endpoint and all key secondary efficacy endpoints, according to the company.

The topline results demonstrate that a single dose of DT120 ODT (Definium Therapeutics) can produce a “meaningful and durable benefit for people with depression. Importantly, these results stand apart from existing treatments, representing a potentially new paradigm for the management of major depression,” principal investigator John Sonnenberg, PhD, clinical psychologist, Northwestern University Feinberg School of Medicine in Chicago, said in a news release.

Rapid, Robust Effect

DT120 (formerly MM120) is a proprietary formulation of LSD developed by MindMed before the company rebranded as Definium Therapeutics earlier this year.

Emerge was a randomized, double-blind, placebo-controlled trial evaluating a single 100-µg dose of DT120 ODT vs placebo in 149 adults with DSM-5-confirmed MDD, a Montgomery-Åsberg Depression Rating Scale (MADRS) total score of at least 26, and a Clinical Global Impression-Severity score of at least 4 at screening and baseline.

At week 6, patients who received DT120 achieved an 8.1-point greater reduction from baseline in MADRS scores than those who received placebo, meeting the study’s primary endpoint (P < .0001). Mean MADRS scores decreased by 13.3 points with DT120 compared with 5.2 points with placebo.

DT120 showed rapid antidepressant effects, with a 14.2-point placebo-adjusted improvement on the MADRS at week 1 (P < .0001). Benefits remained significant at week 12, with a 7.3-point placebo-adjusted improvement (P < .0001), according to the company.

The drug was generally well tolerated, with no serious adverse events and no signal for suicidality reported. Most adverse events were transient and consistent with the expected acute psychoactive effects of LSD.

DT120 is also being evaluated in generalized anxiety disorder. As previously reported by Medscape Medical News, the agent demonstrated rapid and durable reductions in anxiety symptoms in a phase 2b study.

Emerge is the first of two pivotal phase 3 studies evaluating DT120 in MDD. The second study, Ascend, is ongoing and includes both 100-µg and 50-µg dose arms, with topline results expected in 2027.