Inhaled Psychedelic GH001 Significantly and Rapidly Reduces Symptoms in Treatment Resistant Depression in Phase 2b Clinical Trial
GH001, an inhalable 5-MeO-DMT therapy, led to a -15.5 MADRS score reduction by day 8 in patients with treatment-resistant depression.
In the GH001-TRD-201 phase 2b trial of adults with treatment resistant depression (TRD) the investigational psychoactive inhaled mebufotenin therapy GH0001 was associated a with a placebo-adjusted mean change of -15.5 points in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at after 8 days of treatment (P< .001), according to a February 3 news release from drug developer GH Research.1
Professor of Psychiatry, Perelman School of Medicine, University of Pennsylvania
The "ultrarapid" antidepressant effect satisfied the study's primary endpoint, the company stated. Further, the majority of GH001-treated participants achieved remission, with a 57.5% day-8 remission rate compared with 0% in the placebo-treated group (P <.001).
The trial met all secondary endpoints as well, with clinically and statistically significant improvements at day 8 vs placebo on the Clinical Global Impression-Severity (CGI-S) and Hamilton Anxiety Rating Scale (HAM-A), as well as the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF).
Based on preliminary data from the study’s open label extension, participants who achieved symptom remission by study day 8 after an initial active treatment had a 97.1% remission rate at 6 months, according to the news release.1
“Most TRD patients have not benefited from a number of established treatment options and this illness frequently imposes years of insurmountable mental suffering and disabling effects on social and vocational functioning,” Michael E Thase, MD, professor of psychiatry at the Perelman School of Medicine, University of Pennsylvania, said in the GH Research announcement. “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.”1
GH001 is formulated for 5-MeO-DMT administration via a proprietary inhalation approach. 5-MeO-DMT is a naturally occurring psychedelic drug that is part of the tryptamine family and is also known as O-methylbufotenin or mebufotenin.
The investigational treatment was well tolerated, with no serious adverse events (SAEs) reported during the double-blind portion of the trial. All treatment-emergent adverse events (TEAEs) were mild to moderate, and no dissociative state symptoms, sedation, or flashbacks were observed, according to GH Research, nor did researchers report any clinically significant changes in vital signs being monitored during treatment, including heart rate, blood pressure, and ECG.1 Nearly all patients (97.4%) were deemed discharge-ready within 1 hour of the final dose, with no post-discharge restrictions required. Importantly, no evidence of treatment-emergent suicidal ideation or behavior was reported.
As of January 22, 2025, 9 participants remain enrolled in the 6-month OLE, 54 have completed the trial and 18 have discontinued early, the company reported. Only 1 discontinuation was related to an adverse event and no serious adverse events have been observed to date. Among the participants who have completed the study more than three-quarters (77.8%) remained in remission at the 6-month mark. Of that group, the majority (63.9%) received 1 to 4 GH001 treatments over the duration of the study. A final safety analysis will be completed once the OLE is completed.1
Among the estimated 8.9 million adults in the US with major depressive disorder (MDD), approximately 40% have TRD. Of the total financial burden attributed to MDD ($92.7 billion), 47.2% is related to TRD. The TRD share of health care burden is estimated at 56.6%, of unemployment burden, 47.7%, and of productivity burden of medication-treated MDD, an estimated one-third is attributable to TRD.2
During a conference call on Monday, the CEO of GH Research Velichka Valcheva compared the topline findings from GH001-TRD-201 to those with the recently approved inhaled esketamine treatment for TRD, J&J’s Spravato. “When given in combination with antidepressants, Spravato elicited a drop of about -4 points in MADRS, Valcheva noted, additionally pointing to a superior remission rate for GH001,” according to a report on the website BioSpace.3 "The ultra-rapid and profound reduction in depressive symptoms, coupled with sustained remission through infrequent, short treatment visits, positions us uniquely," commented Valcheva in the GH Research press statement.1
References
1. GH Research announces primary endpoint met in phase 2b trial with GH001 in TRD demonstrating -15.5 point placebo-adjusted MADRS reduction. News release. GH Research. February 3, 2025. Accessed February 3, 2025. https://investor.ghres.com/news-releases/news-release-details/gh-research-announces-primary-endpoint-met-phase-2b-trial-gh001
2. Zhdanava M, Pilon D, Ghelerter I, et al. The prevalence and national burden of treatment-resistant depression and major depressive disorder in the United States. J Clin Psychiatry. 2021;82(2):20m13699. doi:10.4088/JCP.20m13699
3. Samorodnitsky D. GH’s inhaled psychedelic succeeds in mid-stage depression trial. BioSpace. February 3, 2025. https://www.biospace.com/drug-development/ghs-inhaled-psychedelic-succeeds-in-mid-stage-depression-trial
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