Definium Therapeutics reports 5.1-point gap in second Phase 3 anxiety study

The U.S. Food and Drug Administration is scheduled to discuss DT120 lysergide in the fourth quarter after Sept. 14 results showed a 5.1-point week-12 advantage over placebo on the Hamilton Anxiety Rating Scale (HAM-A). Definium Therapeutics, Inc. NASDAQDFTX had a US$5.42 billion market value at the Sept. 22, 4 p.m. EDT close, according to the linked Google Finance quote. The New York clinical-stage developer said its 245-person Phase 3 Panorama study in generalized anxiety disorder produced its second positive readout in that indication.

Panorama followed Definium's Voyage readout in generalized anxiety disorder in August and its Emerge readout in major depressive disorder in June. DT120 remains investigational, and Definium expects to file a new drug application in the first half of 2027 after its planned FDA discussion.

The trial assigned 96 adults to 100 micrograms and 97 to placebo. Another 52 were randomized to the 50-microgram arm to help reduce functional unblinding; the lower-dose arm was not designed for a statistical efficacy comparison. The controlled comparison ran for 12 weeks; a 40-week open-label extension continues.

At week 12, the HAM-A score declined by an adjusted mean 9.8 points in the high-dose group against 4.7 points for placebo. The placebo-adjusted difference was 5.1 points, with a p value below 0.0001, according to the Sept. 14 release. Definium also reported meeting three key secondary efficacy endpoints, including a week-one anxiety measure and a day-two clinician severity measure.

Treatment Guesses Complicate Blinding

Definium's same-day presentation says 95 per cent of high-dose recipients and 91 per cent of lower-dose recipients correctly guessed they had received the drug. The company says the dose response supports an effect beyond treatment expectations, but the lower-dose arm was not powered to establish a separate efficacy result.

The FDA's July 2026 psychedelic-trial guidance, docket FDA-2023-D-1987, warns that functional unblinding can introduce expectation bias and make an inert placebo problematic for measuring efficacy. The guidance discusses psychedelic trials generally; it does not assess Panorama.

"Study results should be strongly persuasive and robust across study endpoints to overcome biases that may be introduced by functional unblinding," the FDA said in the guidance.

Treatment-emergent adverse events occurred in 94.8 per cent of high-dose recipients and 62.9 per cent of placebo recipients. The presentation records two serious adverse events in the 100-microgram arm, both deemed unrelated to the drug by Definium. The company reported no suicidality signal.

Participants were monitored for at least eight hours on dosing day. Definium said 94 per cent of high-dose recipients met its end-of-session criteria by hour eight, a measure of how long supervised dosing may take.

FDA Meeting Planned for Fourth Quarter

Definium's Aug. 6 results put cash, cash equivalents and investments at about US$1.1 billion as of June 30. The company projected that these resources would fund operations into 2030 under its operating plan at the time.

Compass Pathways plc NASDAQCMPS is developing COMP360 psilocybin for treatment-resistant depression. Compass announced on April 24 that the FDA had granted rolling submission and review for its planned application. That is a different indication and regulatory stage from Definium's planned meeting.

Read more: FDA psychedelics hearing draws little pushback on future therapeutic use

At its pre-application meeting in the fourth quarter of 2026, Definium expects to discuss the filing it plans for the first half of 2027.