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Emerge Phase 3: DT120 Shows Rapid, Durable Relief in MDD
John Sonnenberg, PhD, reflects on Emerge Phase 3 topline data for DT120 in MDD, including MADRS outcomes, remission rates, and what comes next.
Emerge, a phase 3 trial evaluating a single dose of DT120 (lysergide) ODT 100 µg in adults with major depressive disorder (MDD), met its primary endpoint and all key secondary efficacy endpoints, according to topline results announced by Definium Therapeutics on June 22, 2026.
“I was agnostic about whether psychedelics had true efficacy potential, and now I am convinced as a clinician that they do," said Emerge investigator John Sonnenberg, PhD, clinical psychologist, founder of Uptown Research Institute, and faculty at Northwestern University Feinberg School of Medicine, in an interview with HCPLive.
Emerge, a multicenter, randomized, double-blind, placebo-controlled phase 3 study, enrolled 149 adults (18 – 74 years) with DSM-5-confirmed MDD across 20 sites. Participants received a single dose of DT120 ODT 100 µg or placebo. The trial met its primary endpoint, with a placebo-adjusted MADRS reduction of 8.1 points at week 6 (P <.0001). The placebo-adjusted reduction at week 1 was 14.2 points (P <.0001), and a 7.3-point difference was sustained at week 12 (P <.0001).
Sonnenberg noted that early responses are common in effective antidepressant interventions. The week 1 signal was less notable to him than its persistence.
"The fact that it stood up [for] over 6 weeks and the fact that it persisted to 12 weeks is, from a clinician-researcher standpoint, very impressive," he said.
What the Numbers Don't Fully Capture
Sonnenberg said patients experienced fewer symptoms and reported being less troubled by the ones that remained, an observation that contextualizes the remission data. The 24% remission rate at week 6, compared with 3% for placebo, was statistically significant, though roughly 3 quarters of patients on active drug did not reach remission.
Sonnenberg characterized that gap as consistent with a first-generation result in a new treatment area. He noted that Part B open-label extension data is already informing questions about which patients may benefit from a second dose.
Safety Profile and the Dosing Environment
DT120 ODT was generally well tolerated in Emerge. Of treatment-emergent adverse events, 99% were mild to moderate in severity. No serious adverse events or suicidality signals were identified. Sonnenberg noted that adverse events occurring within the supervised dosing session, rather than at home, allow clinical staff to respond in real time.
The mean time to meeting end-of-session checklist criteria was 5.8 hours. Sonnenberg said most patients at his site were coherent and able to return home independently by hour 6, with the final 2 hours used for observation.
Looking Ahead to Ascend
3Sonnenberg addressed Ascend, Definium's second Phase 3 MDD study, which includes a 50 µg low-dose arm designed to address functional unblinding concerns. Sonnenberg addressed Ascend, Definium's second Phase 3 MDD study, which includes a 50 µg low-dose arm designed to address functional unblinding concerns. He called the design important, pointing to Phase 2b GAD data suggesting that correctly identifying one's dose condition alone does not account for clinical outcomes, and said Ascend is intended to confirm that finding.
"I've never worked on a drug that could create this type of profound change in such a short period of time with the ability to maintain that change for 12 weeks," Sonnenberg said. "This is at a different level."
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