Definium Therapeutics has announced strong results in a phase 3 trial of its single-dosed lysergide (LSD) drug DT120 in treating adults with major depressive disorder (MDD), meeting its primary goal and all key secondary efficacy endpoints in the first trial of its kind.
The results come from the Emerge trial, a randomized, double-blind, placebo-controlled study featuring 149 participants aged 18 to 74 years enrolled across 20 sites. The participants all met specific MDD measures. They needed to have a DSM-5-confirmed diagnosis of MDD, a Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 26 and a Clinical Global Impression–Severity (CGI-S) score of at least 4 at screening and baseline.
The study examined the effectiveness of a single 100 µg dose of DT120 ODT compared with a placebo in alleviating MDD symptoms. In 2023, we covered an earlier trial of lysergide, which had shown positive results in treating general anxiety disorder (GAD).
“The Emerge topline results represent unprecedented and highly differentiated efficacy, demonstrating that a single dose of DT120 ODT can deliver rapid, robust, and durable relief in MDD,” says Rob Barrow, Chief Executive Officer of Definium Therapeutics. “As the first of our Phase 3 studies to report results, Emerge marks a major milestone in our development program and strengthens our confidence in DT120 as a potential best-in-class treatment for mental health disorders.
“These findings could support a fundamentally new approach to treating MDD for patients and providers who continue to face the limitations of existing treatment options,” he adds. “We are deeply grateful to the patients and investigators who participated in this trial. Grounded in decades of scientific research, these results bring us one step closer to potentially delivering a transformative new treatment option as we advance toward FDA submission.”
DT120 ODT – a “pharmaceutically optimized formulation of LSD” – is a fast-dissolving classic serotonergic psychedelic that works by rapidly activating serotonin receptors in the brain.
The tartrate salt form of lysergide, DT120 ODT is currently going through its clinical trial process treating GAD, MDD, and post-traumatic stress disorder (PTSD).
The New York biopharmaceutical company received Breakthrough Therapy designation from the FDA for GAD, and now looks like it could be well on the way to getting its depression-alleviating psychedelic through FDA approval stage.
DT120 ODT is one of a new generation of medications aimed at treating underlying psychiatric and neurological disorders, and the results of this first phase 3 trial have it well positioned to shift this kind of therapeutic into the mainstream spotlight.
In the Emerge trial, patients recorded significantly lower MADRS scores after six weeks of treatment, with an 8.1 difference in score, from a baseline of 35.0 in the treatment group (n=75), compared with a placebo (n=74). This met the company’s main endpoint.
DT120 ODT was also well tolerated, with 99% of adverse events being mild to moderate in severity, and transient, largely occurring on the day patients received their dose.
No new safety issues emerged, including no increase in suicidal ideation.
Emerge is one of two key phase 3 studies putting the drug to the test. The second trial, Ascend, will see participants receive DT120 ODT 100 µg, DT120 ODT 50 µg or placebo. The 50 µg cohort is to “confound participants’ ability to accurately assess the dose condition to which they have been randomized”.
It’s not the only drug of its kind vying for breakthrough FDA approval, with Johnson & Johnson’s Spravato, Compass Pathways’ COMP360, Axsome Therapeutics’ Auvelity and Sage Therapeutics’ Zurzuvae also being developed to fight depression in a revolutionary new way.
However, Definium’s track record has it well placed to seek regulatory approval for DT120 ODT following the results of the Ascend trial.
“Many patients with MDD aren’t helped by existing treatments, often experiencing partial responses, frequent medication changes, and long-term side effects,” says John Sonnenberg, Ph.D., Emerge principal investigator, clinical psychologist and faculty member at Northwestern University Feinberg School of Medicine.
“The Emerge topline results demonstrate that a single dose of DT120 ODT can produce a meaningful and durable benefit for people with depression. Importantly, these results stand apart from existing treatments, representing a potentially new paradigm for the management of major depression,” he adds.
Source: Definium Therapeutics
Fact-checked by Mike McRae
