Definium Therapeutics Highlights Phase III DT120 Gains in Anxiety and Depression

DT120 produced statistically significant improvements after a single treatment in Phase III trials for generalized anxiety disorder and major depressive disorder, with placebo-adjusted gains of 5.1–5.4 points on HAM-A and 8.1 points on MADRS. Ongoing open-label follow-up allows retreatment for patients whose symptoms return; early Part B data show approximately 60%–70% achieving mild symptoms or remission, though full-year durability data are not yet available. Definium plans to consult the FDA on its regulatory submission strategy for GAD and MDD. The company also expects DT120’s initial commercial distribution to rely more heavily on white bagging before potentially expanding buy-and-bill access.

Chief Medical Officer Dan Karlin said the company’s recent Phase III results for DT120 showed statistically significant improvements in generalized anxiety disorder, or GAD, and major depressive disorder, or MDD, following a single treatment, with longer-term open-label portions of the studies still underway. Speaking at TD Cowen’s Sixth Annual Novel Mechanisms in Neuropsychiatry Summit, Karlin discussed top-line results from the Phase III VOYAGE and PANORAMA studies in GAD and the EMERGE study in MDD. Each trial included a 12-week randomized, double-blind primary observation period followed by an additional 40-week Part B period that permits open-label treatment under specified conditions.

Karlin said participants entered the studies with severe symptoms. Patients in the GAD studies had baseline Hamilton Anxiety Rating Scale, or HAM-A, scores of approximately 28, while MDD participants had baseline Montgomery-Åsberg Depression Rating Scale, or MADRS, scores of about 35. The company sought to limit substantial symptoms associated with the alternate condition—depression among GAD participants and anxiety among MDD participants—to more specifically assess DT120’s effects in each indication, Karlin said.

According to Karlin, a single DT120 treatment produced the following placebo-adjusted changes on the primary endpoints: VOYAGE: 5.4-point improvement on the HAM-A at week 12. PANORAMA: 5.1-point improvement on the HAM-A at week 12. EMERGE: 8.1-point improvement on the MADRS at week six. Karlin said each result achieved a p-value below 0.0001. He emphasized that participants received no additional DT120 treatment during the primary efficacy periods and no adjunctive psychotherapy, anxiolytics or antidepressants. In VOYAGE, response and remission rates at week 12 were 43% and 14%, respectively, according to the discussion. PANORAMA reported response and remission rates of 32% and 15%. Karlin said the company’s earlier Phase II trial had shown remission rates approaching 50%, a result he described as unexpected. While acknowledging differences between individual studies, Karlin said Definium viewed the Phase III results as clinically meaningful relative to existing standards of care. PANORAMA also included a 50-microgram control arm, enrolled at half the rate of the full-dose and placebo groups, intended to help assess the potential effects of functional unblinding.

In the ongoing Part B portions of the trials, participants who reach at least moderate illness severity can receive protocol-specified open-label treatment. Karlin said the retreatment thresholds are a MADRS score of 20 for MDD and a HAM-A score of 16 for GAD. Based on data released through week six of Part B, Karlin said the availability of additional treatment has led to a convergence in mild-or-remission outcomes of roughly 60% t...