Definium Delivers Positive Phase 3 Data for LSD Candidate in GAD

NEW YORK – Definium Therapeutics Inc. has released topline results from the first of two Phase 3 studies testing its LSD-based candidate DT120 in adults with generalized anxiety disorder (GAD). The findings add to earlier Phase 3 data in major depressive disorder.

In the Voyage trial, a single 100-microgram dose of DT120 orally disintegrating tablet met the primary endpoint and all key secondary endpoints. Participants who received the drug showed a least-squares mean reduction of 11.6 points on the Hamilton Anxiety Rating Scale (HAM-A) at Week 12, compared with a 6.2-point reduction for those on placebo. The placebo-adjusted difference of 5.4 points was statistically significant (p<0.0001), with a Cohen’s d effect size of 0.81.

The study enrolled 214 adults aged 18 to 74 with a confirmed diagnosis of GAD and a baseline HAM-A score of at least 20. Mean baseline scores were 28.4 in the DT120 group and 27.4 in the placebo group. Separation from placebo appeared as early as Day 2 on the Clinical Global Impression-Severity scale and was maintained through the 12-week double-blind period. Response rates (at least 50% reduction on HAM-A) reached 43% with DT120 versus 16% with placebo.

DT120 was generally well tolerated. Treatment-emergent adverse events were mostly mild to moderate, transient and concentrated on the day of dosing. No new safety signals or suicidality concerns were reported. The trial design included a 40-week open-label extension in which eligible participants could receive additional doses based on symptom severity.

Voyage is one of two Phase 3 studies in the GAD program. The second trial, Panorama, includes a lower-dose control arm and is expected to report results later this year. Definium previously announced positive Phase 3 results for DT120 in major depressive disorder in June. The company holds Breakthrough Therapy designation from the FDA for the GAD indication.

CEO Robert Barrow described the magnitude of the placebo-adjusted change as larger than results typically seen in pivotal anxiety studies. Analyst notes cited by industry coverage characterized the data as meeting or exceeding expectations for effect size in the indication.

The Voyage results supply a second late-stage data set for a single-dose lysergide formulation across two major psychiatric indications. The size of the placebo-adjusted HAM-A change and the early onset of effect will be examined alongside the forthcoming Panorama readout and the ongoing open-label extension. Regulatory discussions and the full safety database from both GAD studies will determine the next steps for the program.