It’s smooth sailing for Definium Therapeutics as the psychedelic biotech charts another win for its LSD candidate, this time in anxiety. The psychedelic previously notched a late-stage victory in depression.
Definium Therapeutics’ single-dose oral LSD candidate DT120 significantly reduced anxiety symptoms compared to placebo in a highly anticipated Phase 3 study. It’s the second late-stage win for the company’s lead asset this summer.
The latest clinical success also beats analyst expectations, with Jefferies writing that the drug has shown “one of the strongest [placebo-adjusted] efficacy benefits” in generalized anxiety disorder (GAD), while Stifel dubbed the data “a clean win.” The findings follow a separate Phase 3 success for DT120 in major depressive disorder (MDD) that was reported in June.
The GAD results are from a 12-week trial of DT120, also called lysergide tartrate, among 214 adults. Dubbed Voyage, the study met its primary and key secondary efficacy endpoints, according to a Wednesday release.
Participants receiving the experimental oral medicine experienced a statistically significant placebo-adjusted reduction of 5.4 points from baseline, as measured by a clinician-administered industry scale of anxiety symptoms. Wall Street analysts had previously projected a 5-point drop and were looking for a strong p-value behind the main endpoint, to which Definium delivered with p < 0.0001.
The efficacy was rapid, with changes starting as early as the second day, according to the New York–based biotech.
Importantly, the drug’s safety was favorable and consistent with past studies, Stifel analysts wrote Wednesday. No serious adverse events occurred, with most patients ready for discharge after six hours. No suicidality signal or behavior was recorded.
“To our knowledge, this is both the largest nominal change and largest standardized effect size ever observed in a pivotal study in GAD,” Definium CEO Rob Barrow said on a Wednesday investor call.
“In a disorder with high prevalence, high burden, high unmet need and no innovation in decades, a single dose of DT120 has shown a rapid and durable effect with a magnitude that is more than twice as large as the drugs approved today,” the CEO said.
The efficacy findings are slightly down from the company’s Phase 2b findings of a 7.7 placebo-adjusted symptom reduction among 40 participants, though analysts said that was largely expected given the larger patient population tested in the Phase 3. Voyage also enrolled fewer patients with comorbid MDD than did the earlier trial, a strategic choice made so Definium could “more clearly tease out the effect of DT120 on GAD symptoms specifically as this is something that helps anticipate any regulatory questions around pseudospecificity,” Stifel wrote.
The new data build on MDD results shared earlier this summer that saw an 8.1-point placebo-adjusted change in symptoms over six weeks—findings that also exceeded analysts’ expectations.
“In our view, single-dose DT120 has produced profound efficacy in 3 Phase II/III datasets across indications,” Jefferies wrote following the newest update.
“While success here was mostly expected, we were pleased to see rapid and consistent efficacy to the ph2b with continued robust durability,” Stifel said.
Definium is now moving DT120 into a 40-week extension phase for GAD. The company is also awaiting GAD findings from a second late-stage study called Panorama, with a readout slated for next month. That trial is slightly larger than Voyage and designed a little differently, with a subtherapeutic dose arm serving as another point of comparison.
Previously, Jefferies forecast at least $1.5 billion peak sales in GAD for DT120, adding in Wednesday’s note that “the Street may start to entertain higher peak sales” opportunities in GAD if confirmed by the second Phase 3 data.
Success in Panorama would position Definium to file a new drug application for GAD “likely sometime in the first half of next year,” Stifel anaylsts wrote. DT120 has secured FDA Breakthrough Therapy designation in the indication.
The LSD candidate is also being developed for post-traumatic stress disorder, with a late-stage trial slated to launch next year.
“A single-dose treatment option delivering meaningful benefits for 12 weeks is a promising step forward not found in today’s therapies,” Brian Barnett, vice chair of psychiatry at Cleveland Clinic and a principal investigator for Voyage, said in a prepared statement from Definium.
“If approved, it could give patients and their physicians a treatment option that works through an entirely different mechanism than anything currently used in clinical practice,” he added.
Definium is a definitive leader in the psychedelics space, second only to Compass Pathways, which holds the potential to bring the first classic psychedelic therapy to market next year. The sentiment surrounding psychedelics has improved significantly this year with strong readouts from Compass and Definium alike, plus federal interest and support.
