CHICAGO — The novel anti-adrenocorticotropic hormone (ACTH) antibody asedebart (Lundbeck) reduced urinary free cortisol (UFC) in people with Cushing disease and was generally well tolerated, according to preliminary phase 2 data.

“These findings suggest that asedebart may be a promising treatment approach for Cushing disease,” Corin P. Badiu, MD, PhD, of the National Institute of Endocrinology and professor at the Carol Davila University of Medicine and Pharmacy, Bucharest, Romania, said at ENDO 2026: The Endocrine Society Annual Meeting. 

Cushing disease is a rare neuroendocrine disorder typically caused by a pituitary adenoma that increases ACTH secretion, leading to excess adrenal cortisol production. Symptoms include obesity, hypertension, infertility, fractures, diabetes, muscle weakness, and dyslipidemia. 

Surgery is the first-line treatment, but more than 30% of patients are ineligible, and recurrence is common among those who undergo the procedure and “current pharmacologic treatments are limited,” Badiu noted. 

He presented preliminary data from BalanCeD, a multicenter, open-label titration trial of asedebart, a first-in-class humanized monoclonal antibody that inhibits ACTH signaling to reduce excess cortisol production. 

The study includes three phases: an intravenous titration phase lasting up to 24 weeks; a subcutaneous phase, including dose titration for up to 40 weeks and maintenance for 8 weeks; and a 52-week extension period. Treatment will then be discontinued, followed by 16 weeks of observation. 

Early Signs of Efficacy 

The study enrolled 12 adult participants with confirmed Cushing disease, evidence of pituitary-derived ACTH excess, and baseline UFC greater than 1.5 times the upper limit of normal. One participant died early in the study from a previously undiagnosed dilated cardiomyopathy that was considered unrelated to treatment. 

Among the remaining 11 participants, mean age was 45.7 years and all but one were women. Mean BMI was 33.8. Medical histories included insulin resistance (66.7%), prior pituitary tumor or intervention (58.3%), obesity (58.3%), hypertension (58.3%), and dyslipidemia (25%). 

Of the eight participants who completed intravenous titration with asedebart, seven achieved normalization of mean UFC.

Adverse events were consistent with the drug’s mechanism of action and included infections and infestations, musculoskeletal and connective tissue disorders, endocrine disorders, and metabolism or nutritional disorders, occurring in three individuals each.

Treatment-emergent adverse events included glucocorticoid deficiency, peripheral edema, and vitamin D deficiency in two participants each. Osteoarthritis and cystitis occurred in one participant each. 

Overall, three participants experienced four serious adverse events: dilated cardiomyopathy, lumbosacral radiculopathy, osteoarthritis, and glucocorticoid deficiency. No hypersensitivity reactions were reported. 

Among the two participants with glucocorticoid deficiency, hypocortisolism was mild and transient. One received hydrocortisone and recovered within 12 days. The other experienced three asymptomatic episodes that resolved with intermittent hydrocortisone over 3-8 days, Badiu reported. 

He acknowledged that the study’s open-label design and small sample size were important limitations. The next step will be to proceed with the subcutaneous administration phase, he said.

An Exciting Molecule 

Asked to comment, Roberto Salvatori, MD, professor of medicine at Johns Hopkins University School of Medicine and director of the pituitary clinic at Johns Hopkins Hospital in Baltimore, described asedebart as “an exciting molecule.” 

However, he noted that Crinetics Pharmaceuticals is developing a once-daily oral melanocortin type 2 receptor antagonist that selectively blocks ACTH activity at the adrenal cortex and is also in phase 2 development. 

“I think the strategy here, with asedebart titration, is going to be a little difficult, and I think ‘block and replace’ will probably be a better approach, but it is very early,” Salvatori said. “It’s an exciting option.” 

Badiu reported serving as a clinical trial investigator for Lundbeck, Alexion, Corcept, and Novo Nordisk. Salvatori reported consulting relationships with Crinetics, Chiasma, and Camurus. 

Miriam E. Tucker is a freelance journalist based in the Washington DC area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR’s Shots blog, and Diatribe. She is on X (formerly Twitter) @MiriamETucker and BlueSky @miriametucker.bsky.social