Following the first late-stage win in a Phase III programme evaluating Definium Therapeutics’ lysergic acid diethylamide (LSD)-based psychedelic in major depressive disorder (MDD), analysts and researchers are touting the drug’s potential as a game-changing therapy in the indication.
This comes after the orally disintegrating therapy, dubbed DT120 (lysergide tartrate), triggered a statistically significant 8.1-point, placebo-adjusted improvement from baseline in patient depression symptom scores at week six during the Phase III Emerge study (NCT06941844) – meeting the trial’s primary endpoint and “beating the effect size of all the approved therapies” for MDD, according to Jefferies analysts.
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DT120’s impact on depression symptoms also had a rapid onset, with treated patients experiencing a placebo-adjusted 14.2-point reduction in depression scores at the one-week mark. In conversation with Clinical Trials Arena, Dr Keith Heinzerling, CSO, TRIP Clinics at Psychedelic Science Institute, and the Emerge study investigator, said a drug with this trait could be highly useful for patients with MDD, as the delay in treatment effect associated with most existing therapies remains a notable challenge.
According to GlobalData neurology analyst, Philippa Salter, DT120’s ability to provide rapid efficacy from a single dose should especially appeal to patients who don’t want to be locked into long-term maintenance treatment.
On top of its quick onset of efficacy, a single dose of DT120 also delivered durable impacts on depression scores over a longer-term period, as patients treated with the drug demonstrated a 7.3-point, placebo-adjusted depression score improvement from baseline at week 12.
The treated patients group also tolerated the psychedelic medicine well, with 99% of treatment-emergent adverse events (TEAEs) falling into the mild or moderate range. No patients experienced an increase in suicidal behaviour or ideation, and discontinuations were “low and comparable” between treatment groups, though Definium has yet to provide details on exact rates.
Next steps for DT120
Following DT120’s Phase III win, Definium is looking ahead to the readout from its other late-stage, two-part MDD trial, Ascend (NCT07592689), which is exploring the drug’s efficacy and safety at varying doses.
Definium is also developing the psychedelic for potential use in generalised anxiety disorder (GAD), with the biotech expecting topline readouts from the Phase III Panorama (NCT06809595) and Voyage (NCT06741228) studies in Q3 2026.
DT120 piques expert interest
With positive data in hand for DT120 in MDD, it appears that Definium is becoming an appealing choice for investors, as the biotech’s stock value jumped nearly 50% from $24.48 at market close on 18 June to $36.67 at the same time on 22 June, following the Emerge data debut.
This comes as Jefferies analysts note that a single dose of the psychedelic has produced “one of the most profound Phase II/III GAD datasets, with similar “outsized efficacy in MDD as well”.
As a researcher and clinician, Heinzerling also voiced his excitement about the data generated for DT120 thus far, noting that he’s not sure if “he could have asked for more” from the first Phase III trial. Heinzerling added that, based on the data generated thus far, he would “be ready to treat MDD with pharmaceutical LSD tomorrow” if it were to secure approval, and that there are no current signals in the data to suggest that the drug couldn’t hold a place in the frontline treatment setting.
However, Salter caveats that a novel, single-dose therapy like DT120 will likely be “priced significantly higher than available therapies for MDD”. This means the drug may see wider use in patients with severe disease later down the treatment line who don’t respond to at least two prior antidepressants.
Building infrastructure for psychedelic administration
While psychedelic therapies like DT120 and Compass Pathways’ COMP360 continue to make waves in the neuropsychiatric space, experts are still raising concerns about the potential administration of these therapies and the in-clinic requirements that centre this emerging modality.
Previously, experts told Clinical Trials Arena’s sister publication, Pharmaceutical Technology, that the implementation challenges associated with psychedelic therapies are likely to persist, with some warning that there is a “risk of developing a two-tiered system, wherein those that can afford treatment through private markets receive it, and those that can’t afford it don’t.”
In a statement to Clinical Trials Arena, a Definium spokesperson said: “We are proactively positioning for access and reimbursement with plans to leverage established and emerging practice patterns and existing administrative pathways to enable timely market uptake.”
“The ultimate goal here is to bring forward a medicine that is accessible – meaning psychiatrists are prescribing and there is reimbursement for people who are in distress, regardless of their socioeconomic circumstances.”
If psychedelic therapies like DT120 and COMP360 were to secure approval, Heinzerling believes that their debut on the market will lower barriers to psychedelic research, which have traditionally been difficult to navigate due to the Schedule I controlled substance status of drugs like LSD or psilocybin.
