Asedebart normalizes cortisol levels in most Cushing’s patients: Data
Experimental therapy generally well tolerated during first part of Phase 2 trial
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Lundbeck’s experimental therapy, asedebart, brought cortisol levels back to normal in most adults with Cushing’s disease and was generally well tolerated when given as an intravenous (into-the-vein) infusion, according to preliminary data from the first part of an ongoing Phase 2 clinical trial.
The BalanCeD (NCT06471829) study, which is currently recruiting participants, is evaluating asedebart in up to 18 adults ages 18 to 70 with Cushing’s disease. The therapy targets adrenocorticotropic hormone (ACTH), which is responsible for driving excess production of the hormone cortisol in Cushing’s disease.
The preliminary findings were presented in an oral session at this year’s Endocrine Society’s Annual Meeting, held June 13 to 16 in Chicago.
“The data from the ongoing Phase II study highlight the potential of direct ACTH neutralization as a novel therapeutic approach in Cushing’s disease, a neuroendocrine condition where major unmet medical needs remain,” Johan Luthman, executive vice president and head of research and development at Lundbeck, said in a company press release.
Asedebart neutralizes key hormone before it reaches adrenal glands
Cushing’s disease is caused by a tumor in the pituitary gland, a small organ at the base of the brain, that releases excessive amounts of ACTH. This hormone, in turn, stimulates the adrenal glands, located above the kidneys, to produce cortisol. Over time, exposure to excess cortisol can lead to a wide range of symptoms and complications, including weight gain, diabetes, and high blood pressure.
Surgery to remove the pituitary tumor is the standard treatment for Cushing’s disease. However, not all patients are eligible for surgery, and some do not achieve lasting remission, meaning their disease returns after initially improving. While several medications are available to lower cortisol levels, Lundbeck said not all patients benefit sufficiently from current treatment options, highlighting an ongoing need for new therapies.
Asedebart, formerly known as Lu AG13909, is a humanized antibody that binds ACTH with high affinity. By neutralizing the hormone before it reaches the adrenal glands, the therapy aims to reduce cortisol production at its source.
BalanCeD is being conducted in three parts. In the first part, or part A, participants receive asedebart through an intravenous infusion, with doses adjusted over time based on their cortisol levels. They then switch to a subcutaneous formulation of asedebart, meaning an injection under the skin, and are monitored during a follow-up period.
The second part, or Part B, is designed to further evaluate the under-the-skin formulation. Participants undergo dose adjustments again to normalize cortisol levels, followed by a maintenance period and additional safety follow-up. An extension phase will allow researchers to continue monitoring the therapy’s long-term safety and effectiveness in participants who complete the earlier stages of the study.
7 of 8 patients had normal urinary free cortisol levels after treatment
The study’s main goal is to determine whether treatment can restore urinary free cortisol (UFC) levels to the normal range. UFC measures the amount of cortisol excreted in the urine over 24 hours and is a key measure of cortisol burden in Cushing’s disease. Researchers are also evaluating the therapy’s safety and tolerability, its processing in the body, whether patients develop antibodies against the treatment, and its effects on other measures of cortisol control.
The data presented at ENDO 2026 came from the intravenous dose-adjustment portion of Part A. At the time of the analysis, 12 participants had enrolled, and eight of the nine who moved on to dose adjustments based on their cortisol levels had completed that process.
According to Lundbeck, seven of those eight participants achieved normal UFC levels after treatment.
The UFC normalization observed in most evaluable patients is very encouraging and strengthens our confidence in asedebart’s continued development in [Cushing’s disease]. The next steps include evaluating a subcutaneous formulation.
Asedebart was generally well tolerated. No allergic reactions were reported. Side effects occurring during treatment were reported in all 12 participants, while serious side effects were reported in three, including one death due to an event deemed unrelated to treatment. Two participants experienced low cortisol levels, but both cases were successfully managed and resolved with treatment.
“The UFC normalization observed in most evaluable patients is very encouraging and strengthens our confidence in asedebart’s continued development in [Cushing’s disease]. The next steps include evaluating a subcutaneous formulation,” Luthman said.
The therapy has received orphan drug designation in the U.S. and Europe for congenital adrenal hyperplasia (CAH), a rare condition that, like Cushing’s disease, is associated with elevated ACTH levels, and in Japan for both Cushing’s disease and CAH. Orphan drug status is granted to therapies being developed for rare diseases and is intended to encourage their development through regulatory and financial incentives.
