DT120 (Lysergide) ODT Receives Breakthrough Therapy Designation for Treatment of MDD

The US Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to Definium Therapeutics for DT120 (lysergide) orally disintegrating tablet (ODT) for the treatment of major depressive disorder (MDD). The designation was supported by the significant unmet need in MDD and results from the Definium phase 3 Emerge study, in which a single 100 µg dose of DT120 ODT demonstrated a statistically significant 8.1-point placebo-adjusted improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 6 (P<0.0001), with durable efficacy through week 12.¹

DT120 ODT, the tartrate salt form of lysergide, is an ergoline derivative belonging to the group of classic serotonergic psychedelics, which acts as a partial agonist at serotonin-2A (5-HT2A) receptors.

"Securing our second Breakthrough Therapy designation, closely following the unprecedented results from our phase 3 Emerge study, underscores the potential of DT120 to meaningfully transform the treatment landscape for people living with serious mental health disorders," said Rob Barrow, the chief executive officer of 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. Our focus remains on developing innovative therapies that have the potential to expand treatment options and improve outcomes for the millions of people who continue to seek meaningful relief."

Breakthrough Therapy Designation for GAD

This is the second Breakthrough Therapy designation from the FDA for the DT120 development program; Breakthrough Therapy designation was previously granted for the treatment of generalized anxiety disorder (GAD). The phase 3 trial in GAD, upon which the FDA designation was based, met its primary and all key secondary endpoints, with benefits emerging within days of dosing and holding through the 12-week trial period. The Voyage trial enrolled 214 participants aged 18 to 74 across 35 US sites; all participants had a DSM-5-confirmed diagnosis of GAD (via clinical assessment and the Mini-International Neuropsychiatric Interview) and a baseline HAM-A score of at least 20. In the study, participants were randomly assigned 1:1 to a single 100 µg dose or placebo for a 12-week double-blind period (Part A) followed by a 40-week open-label extension (Part B), during which participants were potentially eligible for up to 4 additional doses of DT120 ODT based on symptom severity.^2,3

Concluding Thoughts

Definium is also exploring DT120 ODT for the treatment of other serious brain health disorders, such as posttraumatic stress disorder (PTSD). The treatment is designed to provide faster absorption and onset of transient cognitive, perceptual, and affective changes; improved bioavailability; and a lower incidence of gastrointestinal adverse effects. Investigators believe it may help address the serious unmet need in MDD and other disorders.

References

1. Definium Therapeutics receives Breakthrough Therapy designation for DT120 (lysergide) orally disintegrating tablet (ODT) in major depressive disorder (MDD) following positive phase 3 results. News release. September 8, 2026. Accessed September 8, 2026. https://ir.definiumtx.com/news-events/press-releases/detail/247/definium-therapeutics-receives-breakthrough-therapy-designation-for-dt120-lysergide-orally-disintegrating-tablet-odt-in-major-depressive-disorder-mdd-following-positive-phase-3-results

2. Definium Therapeutics Announces Positive Topline Results from Phase 3 Voyage Study of DT120 ODT in Generalized Anxiety Disorder. News release. August 12, 2026. Accessed September 8, 2026. https://www.businesswire.com/news/home/20260812579720/en/Definium-Therapeutics-Announces-Positive-Topline-Results-from-Phase-3-Voyage-Study-of-DT120-ODT-in-Generalized-Anxiety-Disorder

3. Duerr HA. DT120 (Lysergide) shows rapid, lasting relief for generalized anxiety in phase 3 trial. Psychiatric Times. August 12, 2026. https://www.psychiatrictimes.com/view/dt120-lysergide-shows-rapid-lasting-relief-for-generalized-anxiety-in-phase-3-trial