Autobahn Posts Positive Data for Elunetirom in Bipolar Depression

Autobahn Therapeutics has reported positive topline data from the Phase 2 AMPLIFY-BD study evaluating elunetirom (ABX-002) as an adjunctive treatment for bipolar I and bipolar II depression. The investigational therapy achieved a statistically significant 16.8-point reduction in Hamilton Depression Rating Scale (HAMD-17) scores at Week 6 (p<0.001), alongside a 75% response rate and a 50% remission rate.

Improvements emerged by Week 2, highlighting the potential for rapid antidepressant activity in a patient population with substantial unmet need.

The results follow the recent U.S. FDA Fast Track designation granted to elunetirom for adjunctive treatment of bipolar depression and provide further support for the drug’s ongoing development program.

Trial Design and Scope

AMPLIFY-BD was a six-week, open-label Phase 2 study that enrolled 21 adults with bipolar I or bipolar II disorder experiencing moderate-to-severe depressive episodes. Participants received once-daily oral elunetirom in addition to stable mood stabilizer and/or atypical antipsychotic therapy.

The primary endpoint assessed change from baseline in HAMD-17 total score at Week 6. Secondary measures included response and remission rates, functional outcomes, patient-reported assessments, and exploratory neuroimaging analyses using resting-state functional MRI (rs-fMRI).

Efficacy and Neurobiological Findings

Elunetirom demonstrated rapid and sustained antidepressant effects throughout the study. Mean HAMD-17 scores declined by 9.7 points at Week 2 and 13.7 points at Week 4 before reaching a 16.8-point reduction at Week 6, with all improvements achieving statistical significance.

At Week 6, 75% of patients achieved response and 50% achieved remission. Significant improvements were also observed across clinician- and patient-reported measures evaluating symptom severity, daily functioning, productivity, and social engagement. Patients with atypical depression features showed similarly meaningful benefits.

Exploratory rs-fMRI analyses revealed statistically significant changes in brain functional connectivity between baseline and Week 6. These findings provide objective neurobiological evidence consistent with the observed clinical improvements, although confirmation in larger controlled studies will be needed.

Regulatory Pathway and Future Development

Elunetirom was generally well tolerated, with all treatment-related adverse events classified as mild to moderate. No severe or serious treatment-related adverse events were reported.

The therapy is an oral, once-daily, brain-penetrant small molecule prodrug that selectively targets thyroid hormone receptors in the central nervous system. By improving mitochondrial function, increasing cellular energy production, and promoting neuroplasticity, elunetirom may deliver antidepressant benefits while minimizing peripheral thyroid-related effects associated with synthetic thyroid hormone therapies.

Regulatory Pathway and Future Development

Roger S. McIntyre, MD, Professor of Psychiatry and Pharmacology at the University of Toronto, said the magnitude of response, rapid onset, and favorable tolerability profile support CNS-targeted thyroid hormone receptor agonism as a promising new treatment approach for depression.

Autobahn plans to present detailed AMPLIFY-BD data at a medical conference later in 2026. The company is also evaluating elunetirom in the ongoing Phase 2 AMPLIFY study (NCT06633016) in major depressive disorder, with topline results expected in the third quarter of 2026. Positive findings could further validate this novel mechanism across a broader range of depressive disorders.

Reference

Autobahn Therapeutics Reports Positive Phase 2 Topline Data for Elunetirom in Bipolar Depression, Demonstrating Rapid, Robust, and Durable Antidepressant Effects – Autobahn Therapeutics