Definium Therapeutics has scored a third straight phase 3 win for its LSD formula, with the psychedelic significantly alleviating anxiety symptoms and setting up an FDA filing next year.
While the Panorama trial did compare Definium’s DT120 ODT to placebo, the study also pitted the 100 μg dose against a 50 μg dose, which is meant to still be psychoactive but not produce any therapeutic benefit. Panorama enrolled 245 patients.
DT120 easily trounced placebo as it did in the phase 3 Voyage trial a month ago, reducing scores on the Hamilton Anxiety Rating Scale (HAM-A) by 9.8 points at week 12 after treatment compared to 4.7 points for the placebo.
This 5.1-point difference between the 100 μg dose and placebo beat the 3.6-point placebo-adjusted mark seen in the 52-patient 50 μg dose arm, though the 50 μg group was not powered for statistical analysis. In the previous Voyage trial, 100 µg DT120 scored a 5.4-point placebo-adjusted reduction in HAM-A score.
DT120 also notched a phase 3 win in major depressive disorder in June. The drug is given in a single eight-hour session during which patients are monitored by a chaperone who guides them through the effects.
“Patients with generalized anxiety disorder often work through two or three medications before finding one they can tolerate, and even then, daily dosing brings its own burden,” Scott Aaronson, M.D., chief science officer at Sheppard Pratt’s Institute for Advanced Diagnostics and Therapeutics and an investigator in the trial, said in Definium's release Monday. “What stands out about DT120 ODT is that a single dose has the potential to hold a response for months without the patient managing a pill every day.”
The Panorama trial also hit all of its key secondary endpoints and revealed no new safety concerns, Definium said in the release.
“You can go an entire career without getting three pivotal wins like this,” Definium CEO Robert Barrow told Fierce. “To get three in 12 weeks has certainly got to be up there amongst the most rapid succession of these readouts for a company of our size.”
Definium now has a meeting set with the FDA for the fourth quarter to discuss a new drug application for DT120 ODT, Barrow added. While the strategy of which indication to file for first will be hashed out with the agency, Barrow is confident that Definium can prevail in both depression and anxiety.
“We feel quite confident in the reliability of those results, regardless of study design and for both of these indications,” the CEO said.
The Panorama trial’s 50 μg control arm was meant to assuage concerns of functional unblinding in psychedelic trials, a hangup that was recently highlighted by the FDA in a new framework published in the New England Journal of Medicine.
On that front, Barrow argued that Definium succeeded. The 50 μg results were similar to those seen in Definium’s prior phase 2 dose-response study, he said.
“At all the doses we tested, there was meaningful recognition of the effects of the drug when people took it,” said Barrow, who noted that there was still separation between the 100 μg and 50 μg doses in phase 3.
“We don't have any question that there's a robust and real drug effect that we're seeing at 100 μg that isn't present to the same magnitude or durability at a lower dose,” Barrow added.
Even with its whirlwind summer behind it, Definium isn’t taking its foot off the gas, Barrow told Fierce. Another phase 3 depression study for DT120 is still ongoing, and the New York biotech has plans to launch a pivotal trial in PTSD next year.
Definium also boasts a pipeline beyond DT120, led by its formulation of MDMA called DT402 that is currently being tested in a phase 2 trial for autism spectrum disorder. The company also has several other drug candidates that are still preclinical, Barrow said.
With psychedelic hype continuing to grow, Barrow said Definium has “the leading position in shaping this field.” But with that great power comes “an enormous degree of responsibility,” the CEO acknowledged.
“Something like this, where it has such a credible opportunity for benefit and also needs a high degree of rigor and focus on the safety and the responsible delivery, is really a unique opportunity,” Barrow said.