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Maintenance Dosing, Safety Shape GH001 Outlook, With Michael E. Thase, MD
In part 3 of an interview, Michael E. Thase, MD, discusses retreatment timing, safety monitoring, and research priorities following phase 2b GH001 data.
In the third part of an interview discussing phase 2b findings of inhaled mebufotenin (GH001) for treatment-resistant depression (TRD), Michael E. Thase, MD, from the Perelman School of Medicine at the University of Pennsylvania, emphasized the importance of maintenance strategies, safety considerations, and future research priorities following rapid antidepressant effects observed in the randomized trial.
“Retreatment will be a reality for most people who have a benefit… I’m telling people, I think it’s going to be every 6 weeks in standard of care,” Thase told HCPLive.
The double-blind phase 2b study of 81 patients demonstrated significant improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) scores at day 8 with GH001 versus placebo (least squares mean difference, −15.5; P < .001), with remission achieved in 57.5% of treated patients and none receiving placebo. However, durability data from the 6-month extension suggested many patients required additional dosing to maintain benefit.
Thase noted that the risk of relapse clustered early after response. The most vulnerable patients began to show symptom worsening within the first month, with a second group relapsing between months 1 and 2. On average, retreatment occurred approximately 6 weeks after the initial treatment, with additional retreatments distributed over the subsequent 4 months. Overall, roughly 90% of patients required ≥ 1 retreatment within 6 months, and individuals who initially responded typically received about 3 retreatments.
He suggested clinicians anticipate intermittent maintenance dosing, potentially every 6 to 8 weeks, while acknowledging variability. Thase also highlighted a potential role for relapse-prevention–oriented psychotherapy during the maintenance phase, hypothesizing that combining circuit “resetting” effects of psychedelics with structured psychotherapy may reduce retreatment frequency and associated costs.
Regarding safety, Thase reported no severe adverse psychoactive experiences among the 81 treated participants. No patients discontinued due to the intensity of effects, though he cautioned that rare “bad trips” may emerge in larger populations. Supportive clinical monitoring during administration may help patients tolerate transient experiences. He also referenced emerging compounds targeting similar serotonergic pathways without hallucinogenic effects.
Looking ahead, Thase identified replication of efficacy as the primary research priority, followed by optimization of long-term dosing strategies. He noted no evidence of dose tolerance in extension data. He concluded by emphasizing caution pending phase 3 trials, particularly those including US sites, stating that “a sufficient level of caution skepticism” remains appropriate while further data are generated.
“This is a project I've been involved with from the beginning, and so it started one day in early 2020, right at the beginning of the pandemic. We couldn't get this done in the US,” Thase said. “[The] next phase will definitely involve US participation…I really want to wait and see…what happens in phase 3 when we get the big US studies [on] how this will look. My final caveat is that there's a lot of work yet to be done.”
Check out part 1 and part 2 of the interview with Thase on the lack of a placebo response and the clinical advantages of GH001, respectively.
Relevant disclosures for Thase include Otsuka Pharmaceutical, Janssen Scientific Affairs, E.R. Squibb & Sons, Eli Lilly and Company, H. Lundbeck A S, Boehringer Ingelheim International GmbH, and ITI, Inc. (d/b/a Intra-Cellular Therapies, Inc.).
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