GH Research PLC (Nasdaq: GHRS) announced positive top-line results from its Phase 2b clinical trial (GH001-TRD-201) evaluating GH001, an inhalable mebufotenin product candidate, for patients with treatment-resistant depression (TRD). The study met its primary endpoint, demonstrating a statistically significant and clinically meaningful reduction in depressive symptoms.
The randomized, double-blind, placebo-controlled trial enrolled 81 patients with TRD, with 40 receiving GH001 and 41 receiving placebo. Psychotherapeutic intervention was not a component of either arm of the trial. The primary outcome measure was the change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score on Day 8.
Significant MADRS Reduction
GH001 demonstrated a significant reduction from baseline of -15.2 points in MADRS total score on Day 8, compared to a +0.3 point change in the placebo group, resulting in a difference of -15.5 points (p<0.0001). This substantial reduction highlights the potential of GH001 as a rapid-acting antidepressant.
Professor Michael E. Thase, MD, Professor of Psychiatry at the Perelman School of Medicine, University of Pennsylvania, commented, "Patients treated with GH001 experienced a difference of -15.5 points in MADRS score at Day 8 compared to placebo, which is truly remarkable. 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."
Secondary Endpoint Results
The trial also met all secondary endpoints, with results consistent with the primary endpoint. Treatment with GH001 led to clinically and statistically significant improvements on the CGI-S, HAM-A, and Q-LES-Q-SF Questionnaire scales on Day 8, compared with placebo. These consistent improvements across multiple measures further support the efficacy of GH001.
Remission Rates and Long-Term Outcomes
A significant proportion of patients treated with GH001 achieved remission, with a 57.5% remission rate on Day 8 compared to 0% in the placebo group (p<0.0001). Furthermore, in the open-label extension (OLE), 77.8% of completers were in remission at the 6-month visit, with the majority (63.0%) receiving only 1-4 GH001 treatments during those 6 months. Patients who achieved remission on Day 8 after their first active treatment had a 91.7% remission rate at 6 months, suggesting a sustained benefit from the initial treatment.
Safety and Tolerability
GH001 was well-tolerated during the double-blind part of the trial, with no serious adverse events (SAEs) reported. All treatment-emergent adverse events (TEAEs) were mild or moderate, and there were no reports of flashbacks or clinically significant changes in vital parameters, including heart rate, blood pressure, and ECG. No dissociative state symptoms or sedation were observed at discharge, and 97.4% of patients were discharge-ready within 1 hour of the last dose. There was no evidence of treatment-emergent suicidal ideation or behavior.
Regulatory and Business Updates
GH Research is also addressing an Investigational New Drug Application (IND) hold for GH001 by the U.S. Food and Drug Administration (FDA). The company has completed requested inhalation toxicology studies and is preparing a full response to the IND hold, planned for submission in mid-2025.
"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 Dr. 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."
