Psychedelic Trial Shows 94% Remission Rate in Depression Study

Highlights

• Gilgamesh’s GM-2505 showed a 94% remission rate in MDD patients by Day 29 of a Phase 2a trial.
• The psychedelic compound is a short-acting 5-HT2A receptor agonist, designed for in-clinic administration.
• Significant MADRS score reductions were observed, with sustained effects through Day 74.
• No serious adverse events were reported during the study.
• Experts noted the strong efficacy, especially considering the active comparator.
• GM-2505 compares favorably to other psychedelic-based depression treatments, including J&J’s Spravato and Compass Pathways’ psilocybin candidate.

Promising Midphase Results for Gilgamesh's GM-2505

Gilgamesh Pharmaceuticals has reported compelling midphase trial results for its psychedelic drug candidate, GM-2505, positioning the biotech firm as a notable contender in the race to revolutionize psychiatric treatments. In a Phase 2a study involving 40 patients diagnosed with major depressive disorder (MDD), the company observed a 94% remission rate in those who received the higher dose of the experimental compound.

The study tested GM-2505, a 5-HT2A receptor agonist, which is known to trigger the psychedelic effects seen in substances like LSD and psilocybin. According to Gilgamesh, GM-2505 was specifically designed to be shorter-acting than traditional psychedelics, with a 45-minute half-life, making it suitable for use within a two-hour, in-clinic treatment framework. This mirrors the model established by Johnson & Johnson’s ketamine-based drug, Spravato.

Trial Design and Dosage Regimens

Gilgamesh enrolled 40 participants and divided them equally into two treatment arms. One group received a 10 mg dose on Day 1 followed by 15 mg on Day 15, while the comparator group received a 1 mg low-dose on Day 1 and also escalated to 15 mg on Day 15.

As reported: “Scores on the Montgomery-?sberg Depression Rating Scale (MADRS) at baseline were 31.9 and 33.4 in the low and high-dose arms, respectively.” By Day 14, the high-dose group experienced a reduction of 21.6 MADRS points, with 70% of patients achieving remission. The low-dose group saw a 12.1-point decrease, with a 25% remission rate.

The improvements continued by Day 29, when both cohorts had received the 15 mg dose. The remission rate climbed to 94% in the high-dose group and 55% in the low-dose cohort. MADRS scores dropped by 28 points and 21.1 points, respectively. “After 74 days, the scores were still down 19.7 and 25.1 points, respectively, in the low- and high-dose cohorts.”

Expert Reactions and Comparisons

Mass General Brigham psychiatrist Maurizio Fava, M.D., commented in the company’s announcement, stating the results “are impressive, in particular the large and sustained remission rates.” He emphasized the “robust effect size” given that the study included an active psychoactive comparator rather than a placebo.

Gilgamesh’s GM-2505 appears competitive when compared with similar therapies. J&J’s Spravato, for instance, achieved a 19.8-point MADRS reduction from a baseline of 37 and a 53% remission rate in its Phase 3 trial. Meanwhile, Compass Pathways' psilocybin candidate reduced MADRS scores by up to 12 points in a Phase 2 trial. While cross-trial comparisons should be approached cautiously, GM-2505’s performance stands out.

A Promising Future for Gilgamesh

Previous research confirmed that GM-2505 induces altered states of consciousness typical of psychedelics. However, the drug’s shorter duration of action may provide a logistical advantage in clinical settings. Gilgamesh, a Fierce 15 winner in 2024, has seen growing financial backing, including a $39 million raise in 2022 and a $65 million partnership deal with AbbVie aimed at advancing next-generation psychiatric therapies.