IMPACT OF GH001 ON DEPRESSIVE SYMPTOMS, ANXIETY, AND QUALITY OF LIFE IN TREATMENT-RESISTANT DEPRESSION: RESULTS FROM A PHASE 2B TRIAL

Background

Treatment-resistant depression (TRD) is associated with persistent symptoms of depression, anxiety, and reduced quality of life, despite a limited number of treatments being available. There is a need for novel, rapid-acting, safe treatments. GH001, a synthetic form of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) for pulmonary inhalation, has demonstrated potential to reduce depressive symptoms in patients with TRD. This abstract reports efficacy data from a Phase 2b trial assessing GH001 on key depression, illness severity, anxiety, and quality of life measures.

Methods

This multicenter trial (NCT05800860) included a 7-day, randomized, double-blind, placebo-controlled part (Part 1) and a 6-month open-label extension (OLE; Part 2). In Part 1, patients with TRD were randomized 1:1 to receive an individualized dosing regimen (IDR) of up to three escalating doses of GH001 (6, 12, and 18 mg) or placebo IDR on a single day, with a 1hour interval between doses. The second or third dose of the IDR was administered if the previous dose was well tolerated according to the trial physician’s judgement (based on vital signs and adverse events) and if the patient did not achieve an intense psychoactive effect (defined as a mean score of ≥75 on the Peak Experience Scale) following the previous dose. In Part 2, patients could receive up to five GH001 IDR treatments as needed based on the patients’ Montgomery-Åsberg Depression Rating Scale (MADRS) score, and safety and tolerability of previous dose(s). This trial was conducted under the supervision of qualified healthcare professionals, providing psychological support per standard-of-care, but without any planned psychotherapeutic intervention before, during, or after dosing. Efficacy was assessed using MADRS (primary endpoint), Clinical Global Impression-Severity (CGI-S), Hamilton Anxiety Rating Scale (HAM-A), and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) on Day 1 (baseline and 2 hours post-dose), Day 2, Day 8, and all scheduled OLE visits (Day 15 and monthly up to Month 6/end of treatment). Clinician rated assessments were completed by an independent blinded rater. Efficacy results were summarized descriptively.

Results

Eighty-one patients were randomized (GH001 IDR, n=40; placebo IDR, n=41). In Part 1, change in MADRS total score from baseline to Day 8 was significantly greater with GH001 versus placebo (least-squares [LS] mean difference [SE], –15.5 [1.7]; P < 0.0001). This was accompanied by significant improvements in secondary endpoints: LS mean (SE) differences for CGI-S (-2.5 [0.3]), HAM-A (-10.0 [1.4]), and Q-LES-Q-SF (21.4 [2.4]; all P < 0.0001). All 81 patients transitioned directly to the OLE and 63 patients (77.8%) completed the OLE. At Month 6, remission (MADRS ≤10) was achieved by 73.0% of completers, accompanied by significant improvements across secondary efficacy endpoints: mean (SD) change from baseline for CGI-S (-3.0 [1.4]), HAM-A (-13.3 [7.2]), and Q-LES-Q-SF (24.8 [14.1]; all P < 0.0001). Patients received a mean of four GH001 IDR treatments over the trial.

Conclusion

GH001 demonstrated rapid efficacy in reducing depressive symptoms, illness severity, and anxiety symptoms while improving quality of life in patients with TRD in Part 1, with durable responses maintained at 6 months with infrequent retreatments. These findings support further investigation of GH001 for TRD.