Gilgamesh Pharmaceuticals’ psychedelic therapy has boasted a 94% depression remission rate after 29 days in a Phase IIa study.
The trial (NCT06236880) investigated the efficacy, safety and durability of GM-2505, a novel, rapid-acting 5-HT2A receptor agonist and 5-HT releaser in patients with moderate-to-severe major depressive disorder (MDD).
The randomised, double-blind study evaluated GM-2505 in 40 patients who received two doses of the treatment – 10mg then 15mg GM-2505 or a low-dose psychoactive comparator of two doses of 1mg GM-2505.
According to the Montgomery-Åsberg Depression Rating Scale (MADRS) at day 14 after a single dose, patients benefited from a 21.6-point MADRS score reduction compared to a 12.1-point drop in the low-dose cohort. At the same timestamp, 70% of patients receiving 10mg achieved MADRS remission.
At the second time stamp, at 29 days, following a 15mg dose, the high-dose group (10mg + 15mg) reported a 28.0-point drop from baseline, with 94% of patients achieving remission.
The treatment effect was also seen quickly, with an 18.5 MADRS point drop measured within 24 hours. The therapy also proved durability, with improvement observed out to day 74 without any additional treatment.
GM-2505 was well tolerated with no serious adverse events (AEs), with most events being mild and typically resolved within two hours of administration.
Gilgamesh CMO Dr Gerard Marek will be presenting the data at the American Society of Clinical Psychopharmacology's annual meeting in Scottsdale, Arizona, between 27 and 30 May.
This is a notable study in the psychedelic field for several reasons, says Dr Gerard Sanacora, Professor of Psychiatry at Yale University and director of the Yale Depression Research Program.
"The magnitude of symptom improvement observed through the MADRS score reductions is truly impressive. The treatment fits nicely in the two-hour in-clinic framework established by Spravato (esketamine), but with the potential for significantly fewer annual visits. The use of a psychoactive control dose helps to manage the confound of functional unblinding, which is an issue with this class of investigational medicines," Sanacora explained.
Functional unblinding is something that hit psychedelic developer Lykos Therapeutics last year. The company looked set to have the first approved psychedelic in the US; however, the US Food and Drug Administration (FDA) rejected the therapy for several reasons, one of which was functional unblinding.
This challenge is something the psychedelic field is trying to overcome with more intuitive trial designs such as that used by Gilgamesh, by utilising a low dose of the psychedelic as a comparator. Other solutions are also being considered to try and overcome the issue of functional unblinding, as well as other complications that plague psychedelic drug development.
