New York-based Definium Therapeutics (Nasdaq: DFTX) has completed its pivotal Phase III GAD efficacy readouts with a second consecutive positive result, reporting that DT120 ODT (lysergide tartrate), its proprietary orally disintegrating formulation of LSD, met the primary and all key secondary endpoints in the Panorama study. The result gives Definium two replicated Phase III GAD datasets and three positive Phase III readouts overall to support a planned NDA filing in H1 2027, following a pre-NDA meeting with the FDA scheduled for Q4 2026.
Panorama enrolled 245 adults with DSM-5-confirmed GAD and a Hamilton Anxiety Rating Scale (HAM-A) score of at least 20 across approximately 32 sites. Participants received a single dose of DT120 ODT 100 µg, DT120 ODT 50 µg, or placebo in a 2:1:2 ratio. The 50 µg arm was included to mitigate functional unblinding — a methodological challenge inherent to psychedelic trials that the FDA has highlighted in published guidance. The primary endpoint was change from baseline in HAM-A total score at Week 12.
DT120 ODT 100 µg produced a least squares mean HAM-A change of −9.8 versus −4.7 for placebo, a placebo-adjusted difference of −5.1 points (p<0.0001, Cohen's d=0.64). 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. Discontinuation rates were similar across arms (approximately 10-11%), and no drug-related serious adverse events or suicidality signal were observed. The most common treatment-emergent adverse events on dosing day were illusion (68%), nausea (37%), and headache (24%), consistent with prior experience. Across more than 1,000 treatment sessions in the Phase III program, 97% of participants met end-of-session checklist (EoSC) criteria by hour 8.
The 50 µg exploratory 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 Panorama result follows the positive Phase III 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 III Emerge readout in MDD in June 2026. The FDA subsequently granted DT120 ODT a second Breakthrough Therapy Designation for MDD in September 2026, adding to its existing designation for GAD. The effect size in Panorama (d=0.64) is modestly below the d=0.81 observed in Voyage, and cross-trial variability in effect size is expected in replicated studies.