Lundbeck has announced that the European Commission has granted orphan designation to asedebart (Lu AG13909), its investigational anti-ACTH monoclonal antibody, for the treatment of Cushing’s syndrome of endogenous origin. The designation supports the development of asedebart for rare endocrine disorders associated with excessive Adrenocorticotropic Hormone (ACTH) activity.

Cushing’s syndrome of endogenous origin comprises ACTH-dependent and ACTH-independent forms. In ACTH-dependent Cushing’s syndrome, excessive secretion of ACTH is most commonly caused by a pituitary tumour, known as Cushing’s disease, and less frequently by an ectopic ACTH-secreting tumour. Elevated ACTH stimulates the adrenal glands to produce excessive steroid hormones, including cortisol, which can lead to significant metabolic, cardiovascular and neuropsychiatric complications.

Although existing treatments can help control excess cortisol, managing the disease remains challenging. Patients may face limitations related to treatment efficacy, safety and tolerability, while not all patients achieve sustained disease control. Surgery to remove the source of excess ACTH remains the preferred first-line treatment when feasible, but it may not be suitable for every patient or may fail to achieve lasting remission.

Asedebart is a humanised monoclonal antibody designed to specifically bind ACTH with high affinity. By preventing ACTH from binding to the melanocortin 2 receptor in the adrenal glands, the investigational therapy is intended to inhibit ACTH-driven signalling and reduce the production of glucocorticoids, mineralocorticoids and androgens.

Lundbeck is developing asedebart as a potential first-in-class therapy for ACTH-dependent forms of Cushing’s syndrome. Proof-of-concept clinical trials are currently ongoing in Cushing’s disease and classic Congenital Adrenal Hyperplasia (CAH) to evaluate the candidate’s efficacy and safety.

In the European Union, orphan designation is intended to encourage the development of medicines for rare, life-threatening or chronically debilitating diseases. Eligible programmes may receive incentives such as protocol assistance and fee reductions, while approved medicines can receive up to 10 years of market exclusivity for the designated indication, subject to applicable regulatory conditions.

ACTH is a key regulator of adrenal steroid biosynthesis and is therefore considered a potential therapeutic target in diseases characterised by persistently elevated ACTH levels. Through its mechanism of action, asedebart could potentially address disorders driven by chronic ACTH elevation, including Cushing’s disease and CAH.

However, asedebart remains an investigational compound and has not been approved for marketing by any regulatory authority worldwide. Its safety and efficacy have not yet been established.

Lundbeck, which focuses exclusively on brain health, has more than seven decades of experience in neuroscience and develops therapies for neurological and psychiatric diseases.