A stimulator of thyroid hormone receptors in the brain has successfully reduced depression severity in patients with bipolar disorder, positioning its maker Autobahn Therapeutics to speed along to late-stage testing with its ultimate goal of an approval resting further ahead at the finish line.
Autobahn reported this morning that elunetirom, an oral small molecule given once daily, eased depression severity by an average of 16.8 points after six weeks, as measured by the Hamilton Depression Rating Scale.
This result met the primary endpoint of the open-label phase 2 Amplify-BD trial, which enrolled 21 patients with bipolar disorder who were experiencing a depressive episode. Patients took elunetirom in addition to their typical treatment regimen of mood stabilizers and / or antipsychotics.
After six weeks of a daily pill, 75% of patients had responded to treatment and half were in remission, Autobahn said in the release. All adverse events related to elunetirom were mild or moderate, the company added.
The biotech also reported that treatment led to significant changes in brain connectivity. Autobahn plans to share full data from the study at a medical conference later this year.
As an open-label psychiatry study, Autobahn is well aware that the placebo effect—benefits driven by a patient's belief that they've received an effective medicine—could muck up results, CEO Kevin Finney told Fierce Biotech.
“A few things give us real confidence that what we’re seeing is a genuine treatment effect,” Finney said. First is the fact that patients were already receiving other treatments but still saw a boost from elunetirom, he said. “Historical data on those background agents simply don’t produce results of that magnitude.”
The second line of evidence comes from all the trial’s secondary measures, namely assessments of daily life function.
“Patients went from missing roughly three days of work per week at baseline to about half a day by week six,” Finney explained. “As our investigators have framed it, a change of that magnitude in patients already on therapy is difficult to attribute to placebo [effect].”
Autobahn nabbed a fast track designation from the FDA for elunetirom in these patients back in May. The San Diego biotech is also testing the molecule in a placebo-controlled phase 2 study for major depressive disorder.
Autobahn is already prepping for a pivotal phase 3 trial in bipolar depression, Finney told Fierce, with the goal “to bring elunetirom to patients as quickly as we responsibly can.”
“We are already preparing for our next study and plan to hold an end of phase 2 meeting with the agency to align on the path forward,” Finney said. “We anticipate our next trial would be registration-enabling and would begin in the first half of 2027.”
Bipolar disorder is characterized by extreme shifts in mood, with patients swinging from peaks of mania to troughs of depression.
Thyroid hormones and their mimics, like Pfizer’s synthetic compound Cytomel (liothyronine), are often prescribed off-label for depression that doesn’t respond to other therapies. But because they also activate thyroid receptors outside of the brain, these drugs can be plagued by side effects like those of hyperthyroidism, including weight loss, hand tremors and a quickened or irregular heartbeat.
“Synthetic thyroid hormone has been used off-label by psychiatrists for more than 50 years as an adjunctive treatment in depression,” Finney told Fierce. “The historical limitation has never been efficacy. It’s been the peripheral side effects: cardiac effects and disruption of the thyroid hormone axis that come with dosing systemic thyroid hormone.”
By specifically targeting receptors in the brain, elunetirom is designed to avoid the side effects that have limited thyroid hormone therapy’s availability for patients struggling with depression.
“On the measures that matter most for this mechanism, it has looked cardiac-safe and weight-neutral,” Finney said. “It’s built to deliver the part of the biology that helps the brain without the part that historically caused problems in the body.”