FDA, EMA Grant Lu AG13909 Orphan Drug Status for Treatment of Congenital Adrenal Hyperplasia

Lundbeck's novel humanized monoclonal antibody Lu AG13909 has received orphan drug designation from both the FDA and European Medicines Agency for the treatment of congenital adrenal hyperplasia (CAH), a rare autosomal recessive disorder affecting approximately 1 in 14,000-18,000 live births globally. CAH is characterized by impaired cortisol production and elevated levels of adrenocorticotropic hormone (ACTH).¹

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The company announced on June 24, 2025, that the FDA granted orphan designation on May 12, 2025, followed by EMA approval on June 20, 2025.¹ Lu AG13909 represents a first-in-class anti-ACTH antibody approach for treating conditions characterized by high levels of the hormone that lead to additional adrenal hormone imbalances, according to the company announcement.¹

Lundbeck said it is expanding an ongoing phase I/II open-label clinical trial to evaluate the efficacy and safety of Lu AG13909 in adults with classic CAH. The trial will enroll participants across North America and 7 European countries, with initial sites opening in late June 2025.¹

"CAH is a life-long condition, requiring constant management. Many existing treatments focus on controlling cortisol levels, however these options are often complicated by side effects," Johan Luthman, EVP and head of research and development at Lundbeck, said in the announcement. "The orphan drug designation for Lu AG13909, reflects the program's innovative approach, as well as the high medical need to find new treatments for CAH."¹

The expanded trial will recruit men and women aged 18 years and older to 70 years with classic CAH treated with stable glucocorticoid dosing. Participants will receive monthly intravenous administrations of Lu AG13909 and will be divided into 2 cohorts: those with hyperandrogenemia and those with normal androgen levels but requiring supraphysiologic glucocorticoid doses. An optional open-label extension allows participants to receive monthly Lu AG13909 administration for 12 months.¹

Lu AG13909 has high and specific affinity for ACTH, blocking ACTH binding to the melanocortin 2 receptor in adrenal glands. The effect is inhibition of neurohormonal ACTH signaling, a mechanism decreases secretion of glucocorticoids, mineralocorticoids, and androgens from the adrenal glands.

Animal studies demonstrated significant and durable reductions of corticosterone/cortisol and aldosterone with Lu AG13909. No adverse effects were observed after 6 months of intravenous dosing in these preclinical studies.¹

Classic CAH results from enzyme deficiency, most commonly of 21-hydroxylase, affecting adrenal steroidogenesis and leading to cortisol and aldosterone deficiency.² Patients with 21-hydroxylase deficiency face risk of adrenal crisis, a life-threatening condition that contributes to increased mortality throughout life. Balancing physiological glucocorticoid replacement with hyperandrogenism control remains challenging, with risks of long-term consequences from glucocorticoid overtreatment.²

References

1. Lundbeck receives orphan drug designation in the US and EU for Lu AG13909 for the treatment of patients with congenital adrenal hyperplasia. News release. Lundbeck. June 24, 2025. Accessed June 24, 2025. https://news.cision.com/h--lundbeck-a-s/r/lundbeck-receives-orphan-drug-designation-in-the-us-and-eu-for-lu-ag13909-for-the-treatment-of-patie,c4167538

2. Halsey G. The CRF pathway interrupted: Potential to transform CAH care. Patient Care. September 24, 2024. https://www.patientcareonline.com/view/the-crf-pathway-interrupted-potential-to-transform-cah-care