Definium's LSD-Based DT120 Meets Goal in Second Phase 3 Anxiety Trial

Definium Therapeutics said on September 14 that a single dose of DT120, its orally disintegrating tablet formulation of lysergide (LSD), met the primary endpoint of a Phase 3 trial in adults with generalized anxiety disorder (GAD), according to the company's topline announcement.

The study, called Panorama, is Definium's second Phase 3 trial of DT120 in GAD and its third positive Phase 3 readout for the drug. The company reported positive results from the Voyage trial in GAD in August and from the Emerge trial in major depressive disorder in June. The data released so far are company-reported topline results; they have not been published in a journal.

The Panorama results

Panorama enrolled 245 adults aged 18 to 74 at about 32 study centers. Participants were randomized 2:1:2 to a single dose of DT120 at 100 µg, DT120 at 50 µg, or placebo. The 50 µg arm was included to help reduce functional unblinding and was not powered for statistical comparison, the company said.

At week 12, participants on the 100 µg dose had a least squares mean change of -9.8 points from baseline on the Hamilton Anxiety Rating Scale (HAM-A), compared with -4.7 for placebo. That difference of 5.1 points was statistically significant (p<0.0001), with an effect size of 0.64, according to Definium. Mean baseline HAM-A scores were 28.3 in the 100 µg group and 28.0 in the placebo group. The company said changes were seen as early as day 2.

The Pharma Letter described the 5.1-point placebo-adjusted reduction as a moderate effect size.

The trial also met its key secondary endpoints, which measured change on the Clinical Global Impression-Severity scale at week 12 and day 2 and change in HAM-A at week 1. After the 12-week double-blind period, participants can enter a 40-week open-label extension in which they may receive up to four more 100 µg doses based on symptom severity.

Safety and dosing sessions

Definium said most treatment-emergent adverse events were mild to moderate and occurred mainly on the day of dosing. The overall adverse event rate was 94.8% on the 100 µg dose, 96.1% on 50 µg and 62.9% on placebo. The most common events on dosing day in the 100 µg arm were illusion (68%), nausea (37%) and headache (24%). The company said there were no drug-related serious adverse events and no suicidality signal, and that discontinuation rates were similar across the three groups, at about 10% to 12%.

Participants were monitored for at least eight hours on the dosing day. The average time to meet the study's end-of-session criteria was 6.2 hours on the 100 µg dose, and 94% met them by hour 8, according to the company.

"With strong positive results across four complementary studies, we have built a compelling body of evidence that increases our confidence in the potential best-in-class profile of DT120," said Rob Barrow, Definium's chief executive officer.

Next steps

Definium said it has a pre-NDA meeting with the FDA scheduled for the fourth quarter of 2026 and anticipates filing a New Drug Application in the first half of 2027. DT120 has Breakthrough Therapy designation from the FDA for GAD and for major depressive disorder, the company said. Because lysergide is a Schedule I controlled substance, the company noted that it would need rescheduling decisions by the Drug Enforcement Administration and states before any approved product could be legally marketed in the U.S.