Definium Therapeutics has announced positive topline results from the phase 3 Voyage trial of DT120 (lysergide) orally disintegrating tablet (ODT) 100 µg, showing a statistically significant placebo-adjusted reduction of 5.4 points on the Hamilton Anxiety Rating Scale (HAM-A) at week 12 in adults with generalized anxiety disorder (GAD).¹
The result marks Definium's second positive phase 3 readout for DT120 ODT, following the positive Emerge trial results in major depressive disorder (MDD) announced in June 2026.¹ The US Food & Drug Administration (FDA) has granted DT120 Breakthrough Therapy designation for GAD.¹ Voyage is 1 of 2 pivotal phase 3 trials in the program, with topline results from the second trial, Panorama, expected in September.¹
GAD remains one of psychiatry's most undertreated conditions, with limited additional treatment options since 2007.2Yet approximately 26 million adults in the US live with GAD.
"Despite the burden of the disorder, the last new FDA-approved treatment for this condition was nearly 2 decades ago, and many of the patients I see have not found relief despite trying multiple therapies," said Brian Barnett, MD, vice chair of psychiatry, Cleveland Clinic, and a Voyage principal investigator, in a statement.1 “A single-dose treatment option delivering meaningful benefits for 12 weeks is a promising step forward not found in today’s therapies.”
DT120 ODT Efficacy in the Phase 3 Voyage Trial
Voyage is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial evaluating a single 100 µg dose of DT120 ODT versus placebo in adults with GAD.¹ The trial enrolled 214 participants aged 18 to 74 years across approximately 35 US sites, with a DSM-5-confirmed GAD diagnosis and a baseline HAM-A score of ≥ 20.¹
Mean baseline HAM-A scores were 28.4 in the DT120 ODT group (n = 107) and 27.4 in the placebo group (n = 107).¹ The double-blind Part A spans 12 weeks and is followed by a 40-week open-label extension, Part B, during which participants may receive up to 4 additional doses based on symptom severity.¹
For the primary endpoint, the least squares (LS) mean change from baseline in HAM-A score at week 12 was -11.6 with DT120 ODT compared with -6.2 with placebo (LS mean difference of -5.4 points, P <.0001; Cohen's d = 0.81).¹ Key secondary endpoints also reached significance: CGI-S LS mean change at week 12 was -1.0 versus -0.4 (difference, -0.6; P <.0001), HAM-A LS mean change at week 1 was -11.9 versus -4.2 (difference, -7.7; P <.0001), and CGI-S change at day 2 was -1.0 versus -0.2 (difference, -0.8; P <.0001).¹ Definium reported efficacy emerged as early as day 2 and was sustained across all post-baseline timepoints in Part A.¹
"The unprecedented efficacy demonstrated in Voyage should raise the bar for what patients and clinicians expect from GAD treatments," said Rob Barrow, chief executive officer, Definium Therapeutics, in a statement.¹
DT120 ODT Safety and Secondary Endpoints in GAD
Frequently Asked Questions
What did the Voyage trial show for DT120 ODT in GAD?
Voyage met its primary endpoint, with DT120 ODT 100 µg producing a placebo-adjusted 5.4-point reduction in HAM-A score at week 12 (P <.0001; Cohen's d = 0.81).
How is DT120 ODT dosed and administered?
DT120 ODT is a single 100 µg orally disintegrating tablet formulation of lysergide (LSD), built on Catalent's Zydis fast-dissolve technology, with additional doses available during the open-label extension based on symptom severity.
Is DT120 ODT associated with a suicidality risk in GAD?
Definium reported no new safety signals in Voyage, including no suicidality signal or suicidal behavior, with treatment-emergent adverse events mild to moderate and largely confined to the dosing day.
Additional secondary analyses favored DT120 ODT across response and remission measures.¹ HAM-A response rate (≥ 50% reduction) at week 12 was 43% with DT120 ODT versus 16% with placebo (difference, 27%; P <.0001), remission rate (HAM-A ≤ 7) was 14% versus 4% (difference, 10%; P =.0222), and the proportion reaching mild severity or better (HAM-A < 16) was 51% versus 23% (difference, 28%; P <.0001).¹
DT120 ODT was generally well tolerated, with treatment-emergent adverse events mild to moderate in severity, transient, and predominantly occurring on the day of dosing.¹ The company reported no new safety signals and no suicidality signal or suicidal behavior.¹ Using an hourly end-of-session checklist (EoSC) beginning at hour 5 post-dose, the average time to meeting EoSC criteria was 6.4 hours, with a median of 6.1 hours and 92% of participants meeting criteria by hour 8.¹
Definium's second Phase 3 GAD trial, Panorama, adds a low-dose 50 µg arm to the same design, with participants randomized 2:1:2 to DT120 ODT 100 µg, DT120 ODT 50 µg, or placebo.¹ The company stated the low-dose arm is intended to confound participants' ability to accurately identify their randomized dose, building on phase 2b data the company believes demonstrated DT120's clinical activity is not attributable to functional unblinding.¹ Definium is also developing DT120 ODT for PTSD.¹
References
De Berardis D, Serroni N, Carano A, et al. The role of duloxetine in the treatment of anxiety disorders. Neuropsychiatr Dis Treat. 2008;4(5):929-935. doi:10.2147/ndt.s2546
