Elunetirom significantly reduced depressive symptoms and improved functioning in the Phase 2 AMPLIFY-BD trial of bipolar depression.
Written By: Mayuri Vaja, PharmD
Reviewed By: Pharmacally Editorial Team
Autobahn Therapeutics presented complete AMPLIFY-BD (NCT06869187) results at Psych Congress 2026, reporting statistically significant improvements in the primary endpoint and key secondary measures.
The open-label Phase 2 trial enrolled 21 adults with bipolar I or bipolar II disorder who were experiencing a moderate-to-severe major depressive episode. Participants had a mean baseline HAMD-17 score of 25.1, indicating substantial depressive symptom burden.
Elunetirom was evaluated strictly as an adjunctive treatment, not as monotherapy. Participants received oral elunetirom 2.8 µg once daily for six weeks while continuing their existing mood stabilizer and/or atypical antipsychotic regimen, with or without an SSRI or SNRI.
The primary endpoint was the change from baseline in the 17-item Hamilton Rating Scale for Depression (HAMD-17). Mean HAMD-17 scores decreased by 9.7 points at Week 2, 13.7 points at Week 4, and 16.8 points at Week 6, with p<0.001 at each reported time point.
At Week 6, 75% of participants met the study’s response criterion and 50% achieved remission. These rates increased from 38.1% and 14.3%, respectively, at Week 2 and 52.6% and 36.8% at Week 4.
Improvements Extended Across Depressive Symptoms and Function
Elunetirom also improved the HAMD-6 subscale, with a mean reduction of 9.0 points at Week 6 (p<0.001). Individual symptoms, including depressed mood, impaired work and activities, guilt, psychomotor retardation, psychic anxiety, and general somatic symptoms, improved across study visits.
The broader HAMD-29 score decreased by 22.9 points at Week 6 (p<0.001). Clinical Global Impressions-Bipolar Severity scores also improved significantly at all assessed time points, with strong correlations between clinician-rated illness severity and HAMD-17 changes.
Patient-reported outcomes suggested that symptom improvements were accompanied by gains in daily functioning. Sheehan Disability Scale scores improved by 62% from baseline at Week 6 (p<0.001), with significant improvements across work and school, social and leisure activities, and family and home life.
Days lost to illness fell by 85%, from 2.7 days per week at baseline to 0.4 days per week at Week 6 (p<0.001). Symptoms of Depression Questionnaire scores improved by 36%, while Patient Global Impression of Improvement scores showed significant improvement at Weeks 2, 4, and 6.
Elunetirom Was Generally Well Tolerated
Elunetirom was generally well tolerated during the six-week study. No severe or serious treatment-related adverse events were reported. The company also reported no observed weight gain, extrapyramidal symptoms, tardive dyskinesia, clinically meaningful peripheral thyroid effects, or concerning ECG findings.
The most common treatment-related adverse events were dizziness (14.3%), diarrhea (9.5%), and decreased free thyroxine (9.5%).
Elunetirom, also known as ABX-002, is an oral, once-daily, brain-penetrant small-molecule prodrug that targets thyroid hormone receptors in the central nervous system. The approach is intended to engage CNS thyroid hormone signaling while limiting peripheral effects associated with systemic thyroid hormone administration.
Regulatory Path and Development Plans
Elunetirom has received Fast Track designation from the U.S. Food and Drug Administration for adjunctive treatment of bipolar depression. Based on the AMPLIFY-BD results, Autobahn plans to engage with FDA regarding a potential registration pathway.
The company is also evaluating elunetirom as an adjunctive treatment for major depressive disorder in the Phase 2 AMPLIFY trial, registered as NCT06633016.
The AMPLIFY-BD results provide preliminary evidence of improvements in both depressive symptoms and functioning. However, the findings require cautious interpretation because the study included only 21 participants, was open-label, and did not include a placebo or other control group. These design limitations make it difficult to separate the drug’s treatment effect from placebo response, natural changes in depressive symptoms, regression to the mean, or effects associated with ongoing background therapy.
Larger randomized controlled studies will therefore be important to establish the magnitude and durability of elunetirom’s treatment effect and to further characterize its safety profile in bipolar depression.
Reference
Autobahn Therapeutics Reports AMPLIFY-BD Results for Elunetirom in Bipolar Depression, Highlighting Rapid, Robust, and Sustained Improvements in Depressive Symptoms and Functioning, Autobahn, 21 September 2026
Study of ABX-002 for the Adjunctive Treatment of Depressive Episodes Associated With Bipolar Disorder in Adults, ClinicalTrials.gov ID NCT06869187
About the Writer
Mayuri Vaja (Linkedin) is a Pharm.D professional with a strong interest in clinical research, pharmacovigilance, and medical writing, supported by certifications in pharmacovigilance and academic projects exploring AI in healthcare and drug safety.
With a growing focus on evidence-based healthcare and scientific communication, she is developing expertise in clinical research and translating healthcare evidence into clear, meaningful content.
As a Pharmacally healthcare writer, Mayuri is committed to creating accurate, research-driven, and clinically relevant healthcare content while continuously strengthening her professional skills.