Definium's DT120 ODT Hits Primary Endpoint in Second Phase 3 GAD Win, Setting Up First Psychedelic NDA for Anxiety
核心洞察
Definium Therapeutics (搜索)' DT120 ODT (搜索) met its primary and all key secondary endpoints in the Phase 3 Panorama trial of 245 adults with generalized anxiety disorder (搜索).
The 100-microgram dose produced a 9.8-point HAM-A reduction versus 4.7 points for placebo at Week 12, a 5.1-point placebo-adjusted difference (p<0.0001, Cohen's d=0.64).
Panorama is the second positive Phase 3 GAD study for DT120 ODT (搜索) and the third positive late-stage readout overall, following Voyage in GAD and Emerge in MDD.
Definium Therapeutics (搜索) reported positive topline results from its Phase 3 Panorama study of DT120 ODT (搜索) in generalized anxiety disorder (搜索) (GAD) on September 14, 2026, delivering a second consecutive late-stage win for the LSD-derived candidate and positioning the company to seek what would be the first FDA approval of a psychedelic drug for anxiety (搜索). Shares of the New York-based biotech rose roughly 20% in Monday's premarket session on the news.
Panorama met its primary endpoint and all key secondary efficacy endpoints. The trial enrolled 245 adults aged 18 to 74 with DSM-5-confirmed GAD and a baseline Hamilton Anxiety (搜索) Rating Scale (HAM-A) score of at least 20 across approximately 32 study centers. Participants were randomized 2:1:2 to a single dose of DT120 ODT (搜索) 100 µg, DT120 ODT 50 µg, or placebo. The 12-week double-blind Part A is followed by a 40-week open-label extension in which eligible participants may receive up to four additional 100-µg doses.
Efficacy Results
The least-squares mean change from baseline in HAM-A total score at Week 12 was −9.8 for the 100-µg arm versus −4.7 for placebo, a placebo-adjusted difference of −5.1 points (p<0.0001) with a Cohen's d effect size of 0.64. The magnitude of benefit is similar to that seen in Definium's first late-stage anxiety (搜索) study and larger than what has been observed with many other anxiety therapies, though cross-study comparisons are difficult.
All three multiplicity-controlled secondary endpoints were met, including HAM-A change at Week 1 (−5.3 points, p<0.0001) and Clinical Global Impression-Severity (CGI-S) change at Day 2 (−0.8 points, p<0.0001), indicating onset within 48 hours of a single administration. Placebo-adjusted improvements at Week 12 included 0.6 points on CGI-S. At Week 12, 32% of DT120 (搜索)-treated patients achieved a HAM-A response versus 14% on placebo, while remission rates were 15% and 4%, respectively. The company said statistically significant differences emerged as early as the second day after administration and were maintained at subsequent assessment points throughout Part A.
The rapid onset contrasts with traditional options such as antidepressants, whose effects take weeks to emerge.
Dose Selection and Functional Unblinding
The 50-µg exploratory arm was included specifically to mitigate functional unblinding — the phenomenon in which participants correctly deduce whether they received active drug based on its characteristic psychoactive effects, a methodological challenge inherent to psychedelic trials that the FDA has highlighted in published guidance. Across both dosage levels, participants demonstrated the ability to distinguish active treatment from placebo.
The 50-µg arm produced a placebo-adjusted HAM-A reduction of approximately 3.5–3.6 points at Weeks 4 and 12 — roughly 50% and 29% lower than the 100-µg arm, respectively. Definium said this dose-response relationship is consistent with its Phase IIb findings and supports the argument that the 100-µg effect is not attributable to functional unblinding alone. The 100-µg dose showed superior efficacy relative to the 50-µg cohort, which CEO Robert Barrow said simplifies regulatory discussions going forward.
Safety and Tolerability
The safety profile remained consistent with earlier clinical investigations. Most treatment-emergent adverse events (TEAEs) were mild to moderate, transient, and predominantly occurred on the dosing day. In the 100-µg group, the overall TEAE rate was 94.8% versus 62.9% for placebo, while discontinuation rates were nearly identical between arms: 10.4% for DT120 ODT (搜索) versus 10.3% for placebo. The most common dosing-day events were illusion (68%), nausea (37%), and headache (24%). No drug-related serious adverse events or suicidality signal were observed.
Across more than 1,000 treatment sessions conducted in the Phase 3 program through September 10, 2026, approximately 97% of participants met end-of-session checklist (EoSC) criteria within eight hours. In the 100-µg arm, the average time to meet EoSC criteria was 6.2 hours, with 94% meeting the criteria by hour eight.
Regulatory Path and Broader Program
Definium has scheduled a pre-NDA consultation with the FDA for the fourth quarter of 2026 and expects to submit a New Drug Application for DT120 ODT (搜索) in GAD during the first half of 2027. DT120 ODT holds FDA Breakthrough Therapy designation for both GAD and MDD, a status designed to accelerate development and review of promising treatments for serious conditions; the MDD designation was granted in September 2026.
Panorama follows the positive Phase 3 Voyage readout in GAD reported in August 2026, in which a single 100-µg dose produced a placebo-adjusted HAM-A reduction of 5.4 points (Cohen's d=0.81), and the positive Phase 3 Emerge readout in MDD reported in June 2026, in which a single 100-µg dose produced an 8.1-point improvement over placebo on a depression rating scale at Week 6, with benefits persisting through Week 12. The effect size in Panorama (d=0.64) is modestly below the d=0.81 observed in Voyage; cross-trial variability in effect size is expected in replicated studies.
Barrow said the outcome strengthens the evidentiary foundation for the drug's mechanism of action, a critical consideration for regulators, noting that roughly a dozen pharmaceutical programs have failed to win FDA approval for GAD over the past two decades.
Beyond GAD, Definium's second confirmatory Phase 3 MDD study, Ascend, is designed to enroll about 165 participants and is expected to produce topline results in 2027. The company also plans to initiate a Phase 3 study, Haven, in post-traumatic stress disorder (搜索) in 2027, enrolling about 200 adults randomized to DT120 ODT (搜索) 100 µg or placebo, with the primary endpoint expected to be change in the Clinician-Administered PTSD Scale for DSM-5 at Week 8.
Mechanism and Formulation
DT120 ODT (搜索) is a proprietary, pharmaceutically optimized orally disintegrating formulation of lysergide (LSD) built on Catalent's Zydis fast-dissolve tablet technology, selected to improve absorption speed, bioavailability, and tolerability and to reduce gastrointestinal side effects relative to conventional oral dosing. The compound acts as a partial agonist at serotonin 5-HT2A receptors, the same pathway targeted by most psychedelic-class candidates in development. The precise therapeutic mechanism is unknown, but hypotheses center on sustained increases in neuroplasticity following acute receptor activation.
The single-dose, supervised-administration model distinguishes DT120 ODT (搜索) from all currently approved GAD pharmacotherapies — SSRIs, SNRIs, and buspirone — which require daily dosing. According to Definium, the last new FDA approval for GAD was duloxetine in 2007. GAD affects approximately 26 million adults in the United States and is typically managed with antidepressants, anxiolytics, and psychotherapy.
Competitive Landscape
No psychedelic compound currently holds FDA approval for GAD or MDD. The closest competitive programs at the pivotal stage in GAD are Sumitomo Pharma and Otsuka (搜索)'s ulotaront (SEP-363856), a TAAR1 (搜索) and 5-HT1A receptor agonist in Phase II/III, and AbbVie's ABBV-932, a dopamine D3-receptor modulator in earlier clinical investigation; neither has Phase III data. UK-based Compass Pathways has reported positive results from two Phase 3 trials of its synthetic psilocybin compound COMP360 in treatment-resistant depression (搜索) and is pursuing a rolling NDA, but targets a different indication.
Definium will present findings from its broader Phase 3 program at Psych Congress 2026, held September 15–19 in New Orleans. Six posters will cover anxiety (搜索) and depression results, DT120 (搜索)'s safety profile, trial design, and suicidal ideation, while Emerge data will feature in a session on emerging trends in depression.