Single-Dose LSD Formulation Hits Primary Endpoint in Phase 3 MDD Trial
Key Clinical Takeaways
- In the phase 3 Emerge study, Definium Therapeutics’ DT120 orally disintegrating tablet (ODT) met the primary and key secondary endpoints for adults with major depressive disorder (MDD).
- The randomized, double-blind, placebo-controlled study enrolled 149 patients aged 18 to 74 years across 20 sites in the United States.
- A single 100 microgram dose produced greater Montgomery-Åsberg Depression Rating Scale (MADRS) improvement than placebo at week 6 and showed reported effects at weeks 1 and 12.
DT120, a proprietary formulation of lysergide (LSD) for treatment of MDD, met both primary and key secondary endpoints in the phase 3 Emerge study, announced manufacturer Definium Therapeutics.
“Many patients with MDD aren't helped by existing treatments, often experiencing partial responses, frequent medication changes, and long-term side effects,” said principal investigator John Sonnenberg, PhD, Northwestern University Feinberg School of Medicine, in a news release.
"The Emerge topline results demonstrate that a single dose of DT120 ODT can produce a meaningful and durable benefit for people with depression."
Study Details
The phase 3, multicenter, randomized, double-blind, placebo-controlled study enrolled 149 patients aged 18 to 74 years across 20 sites in the United States. Patients had a DSM-5 confirmed MDD diagnosis, a MADRS score of at least 26, and a Clinical Global Impression-Severity (CGI-S) score of at least 4 at screening and baseline.
Patients were randomized to receive one single 100 mg dose of DT120 ODT or placebo ODT. The primary endpoint was change in MADRS score at week 6 from baseline compared to placebo. Key secondary endpoints included speed and durability of antidepressant effects.
For change in MADRS score at week 6, participants in the DT120 group showed a least squares (LS) mean change from baseline of -13.3 versus -5.2 for the placebo group (LS mean difference -8.1, p < 0.0001). Antidepressant effect was rapid, with a placebo-adjusted LS mean reduction in MADRS score at week 1 of -14.2 (p < 0.0001). The treatment effect was also durable, with a placebo-adjusted LS mean reduction in MADRS total score of -7.2 at week 12 (p < 0.0001).
DT120 ODT was well tolerated, with nearly all treatment-emergent adverse events ranging in mild to moderate severity, brief, and mostly occurring on day of dosing. Investigators did not flag any new safety signals, including no increase in suicidal ideation. Discontinuation rates in both groups were low.
Investigation into DT120 for MDD is ongoing, with the Ascend phase 3 study currently underway. Ascend includes a low-dose arm that is “intended to confound participants’ ability to accurately assess the dose condition to which they have been randomized.”
DT120 is being developed for other mental health disorders and received Breakthrough Therapy designation from the US Food and Drug Administration (FDA) for general anxiety disorder (GAD).
Clinical Implications
These topline findings are clinically relevant because many patients with MDD experience partial responses, medication changes, and long-term side effects with existing treatments. In this phase 3 study, a single dose of DT120 was associated with rapid and durable reductions in depressive symptoms compared with placebo.
The reported safety profile, including no new safety signals and no increase in suicidal ideation, may be important for clinicians evaluating emerging treatment approaches. Ongoing investigation will help further clarify the role of DT120 in the treatment landscape for MDD.
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