Almost all the patients with depression who received Gilgamesh Pharmaceuticals’ psychedelic drug candidate went into remission, furthering the biotech’s attempt to follow the trail blazed by Johnson & Johnson.
Gilgamesh's phase 2a trial enrolled 40 people with major depressive disorder (MDD) to test GM-2505, an agonist of the 5-HT2A receptor that is central to the psychedelic response to drugs such as LSD and psilocybin. Gilgamesh designed GM-2505 to be shorter acting than psilocybin, opening the door to its use under the two-hour in-clinic framework that J&J established for its ketamine drug Spravato.
Half the patients received 10 mg of GM-2505 on Day 1 and 15 mg of the drug candidate on Day 15. The other 50% of patients began with a low-dose psychoactive comparator of 1 mg before receiving a 15 mg dose on Day 15. Scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline were 31.9 and 33.4 in the low and high-dose arms, respectively.
By Day 14, MADRS scores in the high-dose arm had fallen 21.6 points and 70% of patients were in remission. The mean change on the low dose was 12.1 points, with 25% of patients in remission.
On Day 29, when both cohorts had received a 15 mg dose, 55% of people in the low-dose cohort and 94% of those in the high-dose arm were in remission.
Day 29 MADRS scores were down 21.1 and 28 points, respectively, in the low- and high-dose cohorts. After 74 days, the scores were still down 19.7 and 25.1 points, respectively, in the low- and high-dose cohorts. Gilgamesh included 17 patients in the high-dose analyses at Day 29 and 74, down from the 20 people who completed the Day 14 assessment. The biotech reported no serious adverse events.
Mass General Brigham’s Maurizio Fava, M.D., said in Gilgamesh’s statement that the phase 2a data “are impressive, in particular the large and sustained remission rates.” Fava added that “the robust effect size is compelling given the use of a truly psychoactive comparator in this study.”
J&J linked (PDF) Spravato to a 19.8-point reduction on MADRS from a baseline of 37 points at Week 4 of its phase 3 trial. Almost 53% of patients were in remission. Meanwhile, Compass Pathways linked its psilocybin drug candidate to MADRS reductions of up to 12 points, from a baseline of 32 or 33, at Week 3 of its phase 2 trial. Cross-trial comparisons can be unreliable, but the available data suggest GM-2505 is competitive.
An earlier study found GM-2505 causes altered states of consciousness and other effects associated with the administration of a psychedelic. The 45-minute half-life of GM-2505 differentiates the molecule from psilocybin and could make the treatment easier to incorporate into clinical practice. Fierce Biotech's Fierce 15 2024 winner Gilgamesh raised $39 million in 2022 and pocketed $65 million from AbbVie last year in a pact designed to develop next-gen psychiatric therapies.