Definium Therapeutics' DT120 Hits Phase III Goals in Anxiety Study

DT120 met its primary and key secondary endpoints in Definium’s 245-person Phase III Panorama trial for generalized anxiety disorder, delivering a 5.1-point placebo-adjusted improvement on the HAM-A scale at week 12. The 100-mcg dose produced stronger outcomes than placebo, including higher rates of response, mild-or-better disease status and remission, while effects were maintained among patients who had previously tried multiple GAD treatments. DT120 was generally well tolerated, with no new safety signals or drug-related serious adverse events. Definium plans to meet with the FDA in the fourth quarter and expects to submit an NDA covering GAD and major depressive disorder in the first half of 2027.

Definium Therapeutics NASDAQ: DFTX reported positive top-line results from Panorama, its second Phase III study of DT120 ODT 100 mcgs in generalized anxiety disorder, or GAD. The company said the single-dose treatment met its primary endpoint and all key secondary endpoints, adding to positive pivotal-study results previously reported in GAD and major depressive disorder. Panorama enrolled 245 participants in a 12-week randomized, double-blind study. Patients were assigned in a 2:1:2 ratio to receive a single 100-mcg dose of DT120, a 50-mcg functional-control dose, or placebo. The primary endpoint was change from baseline in Hamilton Anxiety Rating Scale, or HAM-A, total score at week 12.

At week 12, DT120 100 mcgs produced a 5.1-point placebo-adjusted improvement on the HAM-A, with a p-value of less than 0.0001, according to the company. The treatment showed an early effect, with a 5.3-point placebo-adjusted HAM-A improvement at week one. Definium also reported a 0.8-point placebo-adjusted improvement on the Clinical Global Impression-Severity, or CGI-S, scale at day two.

Chief Medical Officer Dr. Dan Karlin said participants entered the trial with substantial disease burden. Baseline HAM-A and CGI-S scores averaged 28 and 4.7, respectively, which he said placed patients in the severe anxiety range. Half of participants had received two or more previous treatments for GAD, while patients had been diagnosed with the disorder for about nine years on average. At week four, patients receiving DT120 100 mcgs showed a 12.3-point mean improvement from baseline on the HAM-A, representing a 7-point placebo-adjusted difference. At week 12, the mean improvement from baseline was 9.8 points.

Definium reported the following categorical outcomes for the 100-mcg arm at week 12: 32% met the response criterion of at least a 50% HAM-A improvement, compared with 14% on placebo. 35% achieved mild-or-better disease status, compared with 17% on placebo. 15% achieved remission, compared with 4% on placebo.

Karlin said the week-12 treatment effect was maintained across analyzed subgroups, including participants who had previously received at least two GAD medications. The trial’s 50-mcg arm was intended as a functional control and was not powered for prespecified statistical comparisons with the other groups. Definium said the lower dose showed a 3.6-point improvement over placebo at weeks four and 12, below the results for the 100-mcg dose. The company said adverse-event profiles and median time to end-of-session clearance were similar between the two active-dose groups.

The company said DT120 was generally well tolerated, with no new safety signals and no study drug-related serious adverse events. Definium also reported no suicidal or self-injurious behavior and no indication of increased drug-related suicide risk.