Elunetirom is a small molecule drug taken orally once daily. After six weeks of treatment, patients' depression severity decreased by an average of 16.8 points as measured by the Hamilton Depression Rating Scale.
Mechanism of Action and Trial Design
A drug that stimulates thyroid hormone receptors in the brain has successfully reduced the severity of depression in patients with bipolar disorder. This result enables its developer, Autobahn Therapeutics, to accelerate progression to later-stage clinical trials, with the ultimate goal of obtaining regulatory approval.
Autobahn announced that elunetirom, a once-daily oral small molecule, reduced depression severity by an average of 16.8 points after six weeks (based on the Hamilton Depression Rating Scale).
This result met the primary endpoint of the open-label phase 2 trial called Amplify-BD, which enrolled 21 patients with bipolar disorder experiencing a depressive episode. Patients received elunetirom added to their existing background therapy (mood stabilizers and/or antipsychotics).
Efficacy and Safety Data
After six weeks of daily dosing, 75% of patients responded to treatment and half achieved remission, Autobahn said in a press release. The company added that all adverse events related to elunetirom were mild or moderate.
The biotech also reported that treatment led to significant changes in patients' brain connectivity. Autobahn plans to present the full data from the study at a medical conference later this year.
How to Rule Out Placebo Effect?
Autobahn CEO Kevin Finney told FierceBiotech that as an open-label psychiatry study, the company is well aware that the placebo effect (i.e., patients benefiting because they believe they are receiving an effective drug) could confound the results.
"There are several points that convince us that we are seeing a real treatment effect," Finney said. First, patients experienced additional improvement from elunetirom despite already receiving other treatments. "Historical data from those background therapies simply do not show such a large magnitude of improvement."
The second line of evidence comes from all secondary endpoint measures, particularly assessments of daily functioning.
Finney explained: "Patients went from being absent from work about three days per week at baseline to only about half a day per week by week six. As our investigator said, such a large change is hard to attribute to a placebo effect in patients who are already receiving treatment."
Regulatory Status and Next Steps
Autobahn received FDA rapid track designation for elunetirom in these patients in May of this year. The San Diego-based biotech is also conducting a placebo-controlled phase 2 study in major depressive disorder.
Finney told Fierce that Autobahn is already preparing a pivotal phase 3 trial for bipolar depression, aiming "to bring elunetirom to patients as quickly as we responsibly can."
"We are already preparing the next study and plan to have an end-of-phase 2 meeting with regulators to align on the path forward," Finney said. "We expect the next trial to be registration-supporting and to initiate it in the first half of 2027."
