Definium's Lysergide (DT120) Achieves Unprecedented Phase 3 Victory in Generalized Anxiety Disorder
On August 12, 2026, Definium Therapeutics announced positive topline results from its Phase 3 Voyage study evaluating DT120 (lysergide) Orally Disintegrating Tablet (ODT) 100 µg in adults with generalized anxiety disorder (GAD). The trial met its primary endpoint with high statistical significance, demonstrating a placebo-adjusted reduction of 5.4 points on the Hamilton Anxiety Rating Scale (HAM-A) at Week 12. This represents one of the most robust clinical responses ever recorded in a pivotal trial for GAD.
The success of the Voyage trial follows a separate Phase 3 victory for DT120 in major depressive disorder (MDD) in June 2026 (the Emerge study), establishing a highly successful regulatory trajectory for Definium’s lead psychedelic candidate.
Clinical Efficacy and Safety Outcomes
- Primary Endpoint: Participants receiving DT120 ODT achieved a statistically significant reduction in HAM-A score, with a least-squares (LS) mean change of -11.6 from baseline compared to -6.2 for placebo, yielding a placebo-adjusted difference of -5.4 points at Week 12 (p<0.0001, Cohen’s d=0.81).
- Rapid Onset: The treatment demonstrated a rapid and dramatic effect within the first week, showing a placebo-adjusted difference of -7.7 points (p<0.0001) at Week 1.
- Response and Remission: At Week 12, the response rate (defined as a ≥50% reduction in HAM-A) was 43% for DT120 vs. 16% for placebo (p<0.0001). The remission rate (HAM-A ≤ 7) was 14% for DT120 vs. 4% for placebo (p=0.0222).
- Safety: DT120 ODT was generally well-tolerated with a favorable safety profile, consistent with previous clinical evaluations of lysergide.
What This Means
The 5.4-point placebo-adjusted improvement on the HAM-A scale represents a major clinical breakthrough. Standard-of-care treatments for GAD, such as SSRIs, typically show a placebo-adjusted HAM-A improvement of only 2 to 3 points and require daily dosing. In contrast, DT120 is designed as a single-dose therapy that delivers sustained relief over 12 weeks.
"We have never seen a pivotal study deliver greater than five-point placebo-adjusted change on the HAM-A, and we did this 12 weeks after a single dose of drug," — Definium CEO Robert Barrow, quoted in Fierce Biotech
Definium is currently running a second pivotal Phase 3 trial in GAD, named Panorama, which is expected to report topline results in September 2026. This second study includes a low-dose (50 µg) arm designed to confound functional unblinding and provide a more robust control. If the Panorama trial replicates these findings, it will clear a direct path for a New Drug Application (NDA) submission to the FDA.