Gilgamesh's Psychedelic Drug Shows Promising Results in Depression Trial

Gilgamesh Pharmaceuticals has reported groundbreaking results from its phase 2a trial of GM-2505, a novel psychedelic drug candidate for the treatment of major depressive disorder (MDD). The study, which enrolled 40 patients, demonstrated unprecedented remission rates and significant improvements in depression scores, potentially positioning GM-2505 as a formidable competitor in the rapidly evolving psychedelic therapeutics landscape.

Trial Design and Results

The trial evaluated two dosing regimens of GM-2505, an agonist of the 5-HT2A receptor, which is central to the psychedelic response. Patients were divided into two cohorts:

1. High-dose arm: 10 mg on Day 1, followed by 15 mg on Day 15
2. Low-dose arm: 1 mg (psychoactive comparator) on Day 1, followed by 15 mg on Day 15

Key findings from the study include:

• By Day 14, the high-dose arm showed a 21.6-point reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) scores, with 70% of patients achieving remission.
• On Day 29, after both cohorts received the 15 mg dose, remission rates reached 94% in the high-dose arm and 55% in the low-dose arm.
• MADRS score reductions were sustained through Day 74, with 25.1-point and 19.7-point decreases in the high-dose and low-dose arms, respectively.
• No serious adverse events were reported.

Dr. Maurizio Fava of Mass General Brigham commented on the results, stating, "The data are impressive, in particular the large and sustained remission rates. The robust effect size is compelling given the use of a truly psychoactive comparator in this study."

Competitive Landscape and Market Potential

GM-2505's performance appears competitive when compared to existing treatments:

• Johnson & Johnson's Spravato (ketamine-based) showed a 19.8-point MADRS reduction and 53% remission rate at Week 4 in its phase 3 trial.
• Compass Pathways' psilocybin candidate demonstrated MADRS reductions of up to 12 points at Week 3 in its phase 2 trial.

Gilgamesh designed GM-2505 to have a shorter duration of action than psilocybin, potentially allowing for administration within a two-hour in-clinic framework similar to Spravato. With a 45-minute half-life, GM-2505 could offer practical advantages for clinical use.

The promising results have attracted significant industry attention. In 2022, Gilgamesh raised $39 million in funding, followed by a $65 million deal with AbbVie in 2024 to develop next-generation psychiatric therapies. This partnership and the recent trial results position Gilgamesh as a noteworthy player in the psychedelic therapeutics field.

As the pharmaceutical industry continues to explore novel approaches to mental health treatment, GM-2505's strong performance in this midphase trial suggests that psychedelic-inspired medications may play an increasingly important role in addressing the global burden of depression.