Asedebart gains orphan drug status in Japan, offering potential new treatment for congenital adrenal hyperplasia and Cushing’s disease.
Orphan drug designation has been granted in Japan for asedebart (Lu AG13909) for treating patients with congenital adrenal hyperplasia and Cushing’s disease. (1✔ ✔Trusted Source
Lundbeck receives orphan drug designation in Japan for asedebart for the treatment of patients with congenital adrenal hyperplasia and Cushing’s disease
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Lundbeck announced that Japan’s Ministry of Health, Labour and Welfare granted the designation for the investigational therapy aimed at conditions linked to elevated ACTH (Adrenocorticotropic Hormone) levels.
Congenital adrenal hyperplasia and Cushing’s disease are rare disorders with different causes and clinical characteristics, but both share a common mechanism involving increased ACTH levels.
In congenital adrenal hyperplasia, impaired cortisol production results in persistently elevated ACTH levels, causing excessive adrenal androgen production and making lifelong hormone replacement therapy necessary.
Cushing’s disease, on the other hand, develops due to excessive ACTH production by a pituitary adenoma, leading to chronic cortisol excess.
Global Burden of Congenital Adrenal Hyperplasia & Cushing’s Disease
Congenital adrenal hyperplasia affects nearly 1 in 14,000–18,000 live births globally, while Cushing’s disease has an estimated worldwide prevalence of around 2.2 cases per 100,000 people.
Both disorders carry a considerable disease burden, including metabolic, cardiovascular, and neuropsychiatric complications, and are associated with increased morbidity and mortality. Existing treatment approaches mainly focus on controlling hormonal imbalance, but they often face limitations related to efficacy and tolerability.
“Congenital adrenal hyperplasia and Cushing’s disease are serious, chronic conditions that can significantly affect patients’ lives,” said Johan Luthman, Executive Vice President and Head of Research and Development at Lundbeck.
He added that the investigational program for asedebart highlights Lundbeck’s commitment to rare diseases and endocrinological conditions connected to brain function. He also noted that the program reflects the company’s strategy of directly targeting the underlying disease biology and expressed satisfaction over receiving orphan drug designation for asedebart in Japan.
Asedebart Development Progress
Asedebart is a novel monoclonal antibody that targets ACTH and is currently progressing through clinical development as a potential first-in-class therapy for disorders characterized by excessive ACTH levels.
By focusing on an underlying disease mechanism, the therapy aims to introduce a different treatment approach for managing congenital adrenal hyperplasia. Previously identified as Lu AG13909, asedebart has now received an International Nonproprietary Name and has also secured orphan drug designation for congenital adrenal hyperplasia in both the European Union and the United States.
Lundbeck is conducting proof-of-concept clinical trials to evaluate the safety and efficacy of asedebart in patients with classic congenital adrenal hyperplasia and Cushing’s disease.
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 fully established.
Mechanism Behind Asedebart Action
Asedebart is a humanized anti-ACTH monoclonal antibody designed to recognize ACTH with high affinity. The therapy blocks ACTH from binding to the melanocortin 2 receptor in the adrenal glands, thereby inhibiting ACTH neurohormonal signaling. This action reduces the secretion of glucocorticoids, mineralocorticoids, and androgens from the adrenal glands.
ACTH plays an essential role in adrenal steroid biosynthesis and is therefore considered a promising therapeutic target for disorders marked by elevated ACTH levels. In this setting, asedebart may offer a therapeutic option for conditions associated with chronically increased ACTH.
Challenges in Congenital Adrenal Hyperplasia
Classic congenital adrenal hyperplasia is mainly caused by 21-hydroxylase deficiency, an enzyme deficiency that disrupts adrenal steroid production and leads to cortisol and aldosterone deficiency. Individuals with 21-hydroxylase deficiency face the risk of adrenal crisis, a life-threatening complication that contributes to increased mortality throughout life.
Maintaining the balance between physiological glucocorticoid replacement and controlling hyperandrogenism continues to be difficult, while excessive glucocorticoid treatment may lead to long-term complications.
Neuropsychiatric Effects of Cushing’s Disease
Cushing’s disease is a rare endocrine disorder caused by a pituitary adenoma that secretes excessive ACTH, resulting in chronic cortisol overproduction. The disorder is linked to substantial morbidity and increased mortality, and patients may develop a broad range of physical and neuropsychiatric symptoms.
The primary treatment approach involves surgical removal of the tumor, although not all patients qualify for surgery or achieve long-term remission. Current medical therapies show variable effectiveness and may also present safety and tolerability concerns, emphasizing the need for more effective and well-tolerated treatment options.
Reference:
- Lundbeck receives orphan drug designation in Japan for asedebart for the treatment of patients with congenital adrenal hyperplasia and Cushing’s disease(https://news.cision.com/h–lundbeck-a-s/r/lundbeck-receives-orphan-drug-designation-in-japan-for-asedebart-for-the-treatment-of-patients-with-,c4349497)
Source-Medindia