Dublin-based GH Research plc announced positive results from its Phase IIb clinical trial of GH001, an inhaled formulation of 5-MeO-DMT, for the treatment of treatment-resistant depression (TRD). The trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful reduction in depression symptoms as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS).
The Phase IIb trial included 81 participants, with 40 receiving GH001 and 40 receiving placebo. After eight days, the GH001 treatment arm showed a -15.2 point reduction on the MADRS scale, compared to a +0.3 point gain in the placebo group (p<0.0001). These results highlight the potential of GH001 as a rapid-acting antidepressant.
Rapid and Sustained Response
Notably, GH Research reported "ultra-rapid responses" with GH001. At two hours post-administration, patients experienced a -17.8 reduction in MADRS scores, and a -18.6 reduction after two days. In the open-label extension of the trial, GH001 led to a 77.8% remission rate at six months in patients who completed this section, suggesting a sustained therapeutic benefit.
Safety and Tolerability
The company reported no serious adverse events during the trial. Common side effects included nausea, salivary hypersecretion, paresthesia, headache, and distortions in the sense of taste. Importantly, there were no treatment-related events of suicidal ideation or reports of flashbacks. Most patients were ready for discharge approximately one hour after treatment.
Expert Commentary
Michael Thase, a professor of psychiatry at the University of Pennsylvania and scientific advisor to GH Research, stated that GH001 "has the potential to be a practice-changing treatment," citing its "large and rapid effect, particularly one that may require only infrequent, short 1-3 hours clinic visits."
Comparison to Existing Therapies
GH CEO Velichka Valcheva compared the results to those of Johnson & Johnson’s Spravato (esketamine), an inhaled treatment for TRD. Valcheva noted that Spravato, when given in combination with antidepressants, elicited a drop of about -4 points in MADRS, suggesting a potentially superior efficacy profile for GH001. GH Research views its drug-device inhalation combo product as offering strong differentiation versus Spravato.
Mechanism of Action
GH-001 is an inhalable mebufotenin (5-MeO-DMT) activator of serotonin 5-HT2A and 5-HT1A receptors.
