Lundbeck’s anti‑ACTH antibody asedebart achieved 87.5% UFC normalization in Phase II Cushing’s disease trial, supporting a novel therapeutic strategy
Written By: Nalam Karthik, PharmD
Reviewed By: Pharmacally Editorial Team
Lundbeck has reported encouraging preliminary Phase II results for asedebart (Lu AG13909) (NCT06471829), an investigational anti-adrenocorticotropic hormone (ACTH) monoclonal antibody, in adults with Cushing’s disease (CD). Data presented at ENDO 2026 showed normalization of urinary free cortisol (UFC), a key marker of disease control, in 87.5% of evaluable patients who completed individualized intravenous dose titration.
The ongoing multicenter, open-label Phase II study is evaluating multiple intravenous and subcutaneous dosing regimens of asedebart in adults with ACTH-driven Cushing’s disease of pituitary origin. The findings provide early clinical evidence that directly targeting ACTH may reduce the chronic cortisol excess responsible for much of the disease’s morbidity, mortality, and quality-of-life burden.
Direct ACTH Neutralization Targets the Root Hormonal Driver
Cushing’s disease is a rare endocrine disorder caused by ACTH-secreting pituitary adenomas that trigger excessive cortisol production. Persistent hypercortisolism is associated with cardiovascular disease, metabolic complications, neuropsychiatric symptoms, impaired quality of life, and increased mortality.
Unlike currently available therapies that primarily target cortisol synthesis or cortisol receptor signaling, asedebart directly neutralizes circulating ACTH. The humanized monoclonal antibody binds ACTH with high affinity and blocks its interaction with the melanocortin 2 receptor in the adrenal glands, reducing downstream production of cortisol and other adrenal steroids.
Phase II Data Show High UFC Normalization Rate
At the data cutoff, investigators had enrolled 12 patients, with nine entering the intravenous dosing phase. Eight patients completed individualized dose titration and were included in the responder analysis.
Among these patients, seven (87.5%) achieved UFC normalization, defined as UFC levels of 170 nmol/24 hours or less. UFC normalization is a clinically meaningful endpoint because sustained control of cortisol excess is associated with reduced cardiometabolic risk, improvement in disease-related symptoms, and better long-term outcomes for patients with Cushing’s disease.
The treatment was generally well tolerated, and investigators reported no unexpected adverse events or new safety signals.
All 12 participants reported treatment-emergent adverse events, while serious adverse events occurred in three patients, including one death considered unrelated to treatment. No hypersensitivity reactions were observed. Two patients experienced glucocorticoid deficiency events, which were successfully managed with short-term hydrocortisone therapy.
Lundbeck Advances Subcutaneous Development
According to Johan Luthman, Executive Vice President and Head of Research & Development at Lundbeck, the findings support direct ACTH neutralization as a potentially new therapeutic strategy for patients with Cushing’s disease, where significant unmet medical needs remain despite available surgical and medical treatment options.
The company has advanced the program into Part B of the Phase II study, which is evaluating a subcutaneous formulation of asedebart. The next stage will further assess cortisol reduction, safety, tolerability, pharmacokinetics, and patient experience with subcutaneous administration.
If efficacy and safety are maintained, subcutaneous dosing could provide a more convenient treatment option than intravenous administration, potentially reducing treatment burden for patients requiring long-term disease control.
Asedebart remains an investigational therapy and has not received regulatory approval in any market. The antibody has received Orphan Drug Designation in the United States, European Union, and Japan for Cushing’s disease and congenital adrenal hyperplasia, supporting its development across rare endocrine disorders.
Reference
Lundbeck presents new Phase II asedebart data in Cushing’s disease at ENDO 2026 – H. Lundbeck A/S
About the Writer
Nalam Karthik (LinkedIn) is a healthcare writer and PharmD graduate with interests in pharmacovigilance, drug safety, clinical data analysis, and quality assurance. He is passionate about translating clinical and pharmaceutical knowledge into accessible healthcare content while staying engaged with advancements in drug development and patient safety initiatives.