GH001 Achieves Significant Depression Symptom Reduction in Phase 2b Trial

GH Research announced their phase 2b trial met its primary endpoint, with GH001 providing a significant reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS) score by day 8.

“Patients treated with GH001 experienced a difference of -15.5 points in MADRS score at Day 8 compared to placebo, which is truly remarkable,” said Michael E. Thase, MD, a psychiatry professor at Perelman School of Medicine, University of Pennsylvania, in a statement.

The randomized, double-blind, placebo-controlled phase 2b clinical trial evaluated GH001, an inhalable mebufotenin product candidate, in 40 patients with treatment-resistant depression (TRD), compared with 41 participants on placebo. GH001 is formulated for 5-MeO-DMT administration via a proprietary inhalation approach.

GH001 resulted in a significant -15.2-point reduction from baseline in the MADRS total score on Day 8, compared with an increase of 0.3 points in the placebo group (difference, -15.5 points; P < .0001).

“A novel treatment with such a large and rapid effect, particularly one that may require only infrequent, short 1-3 hours clinic visits, has the potential to be a practice changing treatment,” Thase said.

The trial also met all secondary endpoints, with GH001 leading to clinically and statistically significant improvements on the CGI-S scale, HAMA-A scale, and Q-LES-Q-SF Questionnaire on day 8, compared with placebo.

In the study, GH001 was well tolerated with no reported serious adverse events. In total, 97.4% of patients were ready to be discharged within an hour of their last dose.

All treatment-emergent adverse events were mild or moderate, and there were no observations of flashbacks, significant changes in vital parameters such as heart rate or blood pressure, or dissociative state symptoms. Investigators also did not observe any evidence of treatment-emergent suicidal ideation or behavior, nor sedation.

The trial is ongoing, with 9 patients still on the treatment paradigm as of January 22, 2025. As of now, 54 patients have completed the trial and 18 patients discontinued early, with only 1 discontinuation attributed to an adverse event).

Among the patients who completed treatment, 77.8% were in remission, indicated by a MADRS ≤ 10, at the 6-month visit. Most people who completed the treatment (63%) received 1 – 4 GH001 treatments for 6 months.

"Today, as we share our unprecedented positive Phase 2b data, we celebrate a significant milestone in our journey to interventional psychiatry and pave the way for our future commercial success with GH001 in treatment-resistant depression," said Villy Valcheva, chief executive officer of GH Research. "The ultra-rapid and profound reduction in depressive symptoms, coupled with sustained remission through infrequent, short treatment visits, positions us uniquely."

References

GH Research Announces Primary Endpoint Met in Phase 2b Trial with GH001 in TRD Demonstrating -15.5 Point Placebo-adjusted MADRS Reduction. Globe Newswire. February 3, 2025. https://www.globenewswire.com/news-release/2025/02/03/3019385/0/en/GH-Research-Announces-Primary-Endpoint-Met-in-Phase-2b-Trial-with-GH001-in-TRD-Demonstrating-15-5-Point-Placebo-adjusted-MADRS-Reduction.html. Accessed February 3, 2025.