GH Research Announces Publication of Phase 2b Results for Mebufotenin (GH001) in JAMA Psychiatry and Reports New Finding of Severity-Independent Efficacy in TRD
Rhea-AI Summary
GH Research (Nasdaq: GHRS) reported peer-reviewed Phase 2b results for mebufotenin (GH001) in treatment-resistant depression, published in JAMA Psychiatry on March 25, 2026.
A post hoc analysis in Psychopharmacology Bulletin found efficacy independent of prior antidepressant failures, with Day 8 remission 53.9%–63.6% and Month 6 remission 61.5%–85.7% across subgroups.
Positive
- Day 8 remission 53.9%–63.6% across 2 to ≥5 prior failures
- Month 6 remission 61.5%–85.7% across prior-failure subgroups
- Published in JAMA Psychiatry, providing independent peer-reviewed validation
Negative
- Phase 2b results require pivotal trials before regulatory approval
- Post hoc analysis limits causal inference compared with pre-specified endpoints
News Market Reaction – GHRS
In the Mar 25 session, GHRS gained 1.94%, reflecting a mild positive market reaction. Our momentum scanner triggered 7 alerts that day, indicating moderate trading interest and price volatility.
Data tracked by StockTitan Argus on the day of publication.
Key Figures
Historical Context
| Date | Event | Sentiment | 24h Move | Catalyst |
|---|---|---|---|---|
| Mar 05 | Full-year results & update | Positive | -5.1% | Reported 2025 results, strong GH001 Phase 2b data, and Phase 3 planning. |
| Jan 05 | Clinical hold lifted | Positive | +16.8% | FDA lifted GH001 clinical hold, enabling U.S. enrollment and Phase 3 plans. |
| Jan 02 | IND status preview | Positive | +16.8% | Signaled upcoming IND status and global Phase 3 program update in TRD. |
| Nov 06 | Q3 results & updates | Neutral | -1.3% | Outlined Q3 2025 financials, Phase 2b success, and remaining IND hold topic. |
| Oct 09 | Conference presentations | Neutral | +0.1% | Announced ECNP symposium and posters on long-term GH001 TRD data. |
24h Move is the share-price change in the day after each event; other market factors may also have contributed.
Positive GH001 clinical and regulatory updates have often been met with strong upside moves, while broader earnings updates that include losses have seen more muted or negative reactions.
Recent news flow has centered on GH001’s progress in treatment-resistant depression. A Jan 5, 2026 update on the FDA lifting the clinical hold and enabling a global Phase 3 coincided with a strong positive move. Earlier earnings and business updates in Nov 2025 and Mar 2026 highlighted robust Phase 2b efficacy but also ongoing losses, with weaker price reactions. Today’s peer-reviewed Phase 2b publications extend this clinical narrative by adding severity-independent efficacy data.
Key Terms
phase 2b medical
treatment-resistant depression medical
randomized, double-blind, placebo-controlled medical
open-label extension medical
montgomery-åsberg depression rating scale (madrs) medical
post hoc analysis medical
AI-generated analysis. How Rhea-AI works. Not financial advice.
- Phase 2b results for GH001 in TRD now published and peer-reviewed in JAMA Psychiatry
- New peer-reviewed article in forthcoming issue of Psychopharmacology Bulletin demonstrates that GH001 efficacy is independent of prior antidepressant treatment failures
DUBLIN, March 25, 2026 (GLOBE NEWSWIRE) -- GH Research PLC (Nasdaq: GHRS), a clinical-stage biopharmaceutical company dedicated to transforming the lives of patients by developing a practice-changing treatment in depression, today announced two peer-reviewed publications from its Phase 2b clinical program of GH001 in treatment-resistant depression (TRD): the primary trial results in JAMA Psychiatry, and a new analysis demonstrating that efficacy is independent of the number of prior lifetime treatment failures in a forthcoming issue of Psychopharmacology Bulletin.
JAMA Psychiatry Publication
The peer-reviewed article, titled “GH001 vs Placebo in Patients with Treatment-Resistant Depression” has been published today in JAMA Psychiatry (DOI: 10.1001/jamapsychiatry.2026.0096). The publication includes the complete results from the randomized, double-blind, placebo-controlled Phase 2b trial of mebufotenin in patients with TRD, including all primary and secondary efficacy endpoints, safety and tolerability data, and initial results from the 6-month open-label extension. These results were previously reported in topline form.
“Publication in JAMA Psychiatry provides independent peer-reviewed validation of our Phase 2b findings,” said Dr. Velichka Valcheva, Chief Executive Officer. “This supports our ongoing efforts to advance GH001 into global pivotal trials.”
New Finding: GH001 Efficacy Is Independent of Prior Treatment Failures
A supporting peer-reviewed article, titled “GH001 Efficacy is Independent of Prior Antidepressant Treatment Failures in Treatment-Resistant Depression: A Post Hoc Analysis of a Phase 2b Randomized Controlled Trial,” will be published in a forthcoming issue of Psychopharmacology Bulletin.
In TRD, a well-established finding across multiple treatment modalities is that remission rates decline significantly with each successive antidepressant treatment failure. This pattern, first quantified in the landmark STAR*D trial (see About STAR*D below), represents a fundamental challenge in treating patients with extensive treatment histories. The new analysis of Phase 2b data demonstrates that GH001 does not follow this pattern:
- Day 8 remission rates ranged from
53.9% to63.6% across patients with 2 to ≥5 prior lifetime antidepressant failures, with no decline at higher failure counts; - End of trial/Month 6 remission rates ranged from
61.5% to85.7% across the same subgroups; and - No meaningful correlation was observed between the number of prior lifetime treatment failures and Montgomery-Åsberg Depression Rating Scale (MADRS) improvement at Day 8 (r=−0.13; P=0.44) or among those who completed the 6-month OLE (r=−0.10; P=0.60).
“One interesting, unanticipated finding from this trial is that the benefit of GH001 appeared to be independent of the number of prior lifetime antidepressant failures. Remission rates were consistently high across subgroups – in contrast to the decline seen with each successive treatment that we observed in the STAR*D trial. This suggests patients who have not responded to three or more prior courses of antidepressant therapy might benefit from this novel therapy,” said Michael E. Thase, MD, Professor of Psychiatry, Perelman School of Medicine at the University of Pennsylvania.
Consistent with the findings of this article, GH001 efficacy is also independent from prior treatment failures within the current depressive episode in this Phase 2b trial.
About GH Research PLC
GH Research PLC is a clinical-stage biopharmaceutical company dedicated to transforming the lives of patients by developing a practice-changing treatment in depression. GH Research PLC’s initial focus is on developing its novel and proprietary mebufotenin therapies for the treatment of patients with TRD. Based on the observed clinical activity in our Phase 2b trial, where the primary endpoint was met with a MADRS reduction from baseline of −15.5 points compared with placebo on Day 8 (P<0.0001), we believe that our mebufotenin product candidates have the potential to change the way TRD is treated today.
About GH001
Our lead product candidate, GH001, is formulated for mebufotenin administration via a proprietary inhalation approach. Based on the observed clinical activity in our Phase 2b GH001-TRD-201 trial, where the primary endpoint was met with a MADRS reduction from baseline of −15.5 points compared with placebo on Day 8 (P<0.0001), we believe that GH001 has the potential to change the way TRD is treated today.
About STAR*D
The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial was the largest and most comprehensive prospective study of depression treatment outcomes ever conducted. Funded by the National Institute of Mental Health (NIMH), the trial enrolled 4041 outpatients with major depressive disorder across 41 U.S. clinical sites between 2001 and 2004. The study used a sequential design in which patients who did not achieve remission on an initial antidepressant (citalopram) were moved through up to four successive treatment steps, each involving a switch to or augmentation with a different medication.
STAR*D’s central finding was that remission rates declined progressively with each treatment step:
Forward-Looking Statements
This press release contains statements that are, or may be deemed to be, forward-looking statements. All statements other than statements of historical fact included in this press release, including statements regarding our plans and expectations with respect to our global Phase 3 pivotal program for GH001, strategies and prospects for our business, including the development and therapeutic potential of mebufotenin and GH001, are forward-looking statements. Forward-looking statements appear in a number of places in this press release and include, but are not limited to, statements regarding our intent, belief or current expectations. Forward-looking statements are based on our management’s beliefs and assumptions and on information currently available to our management. Such statements are subject to risks and uncertainties, and actual results may differ materially from those expressed or implied in the forward-looking statements due to various factors, including, but not limited to, those described in our filings with the U.S. Securities and Exchange Commission from time to time. No assurance can be given that such future results will be achieved. Such forward-looking statements contained in this press release speak only as of the date hereof. We expressly disclaim any obligation or undertaking to update these forward-looking statements contained in this press release to reflect any change in our expectations or any change in events, conditions, or circumstances on which such statements are based unless required to do so by applicable law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements.
Investor Relations
Julie Ryan
GH Research PLC
investors@ghres.com
