DT120 (Lysergide) Shows Rapid, Lasting Relief for Generalized Anxiety in Phase 3 Trial

A single dose of DT120 (lysergide), an orally disintegrating tablet (ODT) formulation of LSD, produced a significant and lasting reduction in anxiety symptoms in Voyage, Definium Therapeutics's first phase 3 trial in generalized anxiety disorder (GAD), they announced today.¹ The study met its primary and all key secondary endpoints, with benefits emerging within days of dosing and holding through the 12-week trial period. DT120 was granted FDA Breakthrough Therapy designation for GAD.

Voyage Trial Results: Primary and Secondary Endpoints

Patients on DT120 (n=107)100 µg improved significantly more than those on placebo (n=107) on the trial's primary endpoint, change in Hamilton Anxiety Rating Scale (HAM-A) total score from baseline to week 12: -11.6 vs -6.2, respectively, and a placebo-adjusted difference of 5.4 points (p<0.0001), with a large effect size (Cohen's d=0.81). The drug was generally well tolerated; adverse events were mild to moderate, transient, and clustered on dosing day, with no new safety signals and no suicidality signal reported.

Key secondary endpoints also were met. On the Clinical Global Impression-Severity (CGI-S) scale, DT120 outperformed placebo by 0.6 points at week 12 and 0.8 points at day 2 (both p<0.0001), suggesting clinicians rated patients as meaningfully less impaired almost immediately after dosing. HAM-A improvement was already 7.7 points greater than placebo at week 1.

Other secondary measures reinforced the effect. Response rates (≥50% HAM-A improvement) were more than double those on placebo(43% vs 16%), with just over half of treated patients reaching a mild-or-better symptom level (HAM-A <16) by week 12, compared with roughly a quarter on placebo. Full remission (HAM-A ≤7) was reached by 14% of participants receiving DT120 versus 4% on placebo. Because DT120 produces transient perceptual and affective effects on dosing day, participants were monitored in-clinic; on average, patients met discharge criteria at 6.4 hours post-dose, with 92% cleared by hour 8 — a practical consideration for how the treatment would need to be administered if approved.

"GAD affects approximately 26 million adults in the United States, and when left untreated, can cause chronic, pervasive, and debilitating symptoms that can seriously impact a person's daily life. It is one of the most undertreated conditions in psychiatry," Brian Barnett, MD, vice chair of psychiatry at Cleveland Clinic and a Voyage principal investigator, said in a press statement. "Despite the burden of the disorder, the last new FDA-approved treatment for this condition was nearly two decades ago, and many of the patients I see have not found relief despite trying multiple therapies. A single-dose treatment option delivering meaningful benefits for 12 weeks is a promising step forward not found in today's therapies."

Study Design and Patient Population

Voyage is the second positive phase 3 readout for DT120 ODT, and follows June's Emerge results in major depressive disorder.² 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 randomized 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.

What's Next for DT120?

In Panorama, Definium's second pivotal GAD trial, a 50 µg dose arm will be evaluated to help rule out functional unblinding; data readout is expected in September. If Panorama confirms these findings, DT120 would represent the first new mechanism of action approved for GAD since 2007, positioning Definium for a potential regulatory filing across both indications.

“The unprecedented efficacy demonstrated in Voyage should raise the bar for what patients and clinicians expect from GAD treatments,” Rob Barrow, chief executive officer of Definium Therapeutics, said in a press statement. “Importantly, the consistent, large effect size we’ve now observed across three studies underscores the potential of DT120 to transform psychiatry and usher in a new era of mental health care.”

References

1. Definium Therapeutics Announces Positive Topline Results from Phase 3 Voyage Study of DT120 ODT in Generalized Anxiety Disorder. Press release. Accessed August 12, 2026. August 12, 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

2. Kuntz L. Positive Topline Results From Phase 3 Emerge Study of DT120 ODT in Major Depressive Disorder. Psychiatric Times. June 22, 2026. Accessed August 12, 2026. https://www.psychiatrictimes.com/view/positive-topline-results-from-phase-3-emerge-study-of-dt120-odt-in-major-depressive-disorder