The European Commission has granted orphan designation to asedebart (Lu AG13909) to brain health biopharmaceutical company Lundbeck’s novel investigational anti-ACTH monoclonal antibody (mAb), for the treatment of Cushing’s syndrome of endogenous origin. 

Cushing’s syndrome of endogenous origin includes both ACTH-dependent and ACTH-independent forms. ACTH-dependent Cushing’s syndrome is a rare, serious endocrine disorder caused by excess secretion of adrenocorticotropic hormone (ACTH), most commonly from a pituitary tumour (Cushing’s disease) and less frequently from an ectopic ACTH-secreting tumour1.  

This increase in ACTH causes the adrenal gland to produce higher levels of steroid hormones, glucocorticoids, mineralocorticoids and androgens, leading to a wide range of homeostatic imbalances. One major change is chronic excess of the glucocorticoid, cortisol, which is associated with substantial disease burden, including metabolic, cardiovascular and neuropsychiatric complications, and is linked to increased morbidity and mortality1,2. Current medical therapies can help manage cortisol excess, however significant unmet medical need remains. Disease control remains challenging and treatment options may be limited by variable efficacy, safety and tolerability1,3. 

Milestones for asedebart 

Asedebart is a novel investigational mAb targeting ACTH and is being developed for ACTH-dependent forms of Cushing’s syndrome. It is advancing in clinical development as a potential first-in-class treatment for rare conditions characterised by excess ACTH, with proof-of-concept trials ongoing in CD and classic congenital adrenal hyperplasia (CAH) to evaluate efficacy and safety5-7. 

Previous orphan designations include CAH in the European Union and the United States, and CAH and CD in Japan. 

“Orphan designation in the European Union is an important recognition of both the unmet need in Cushing’s and the scientific rationale behind asedebart,” said Johan Luthman, Executive Vice President, R&D, Lundbeck. “The asedebart programme is a good representation of the type of strong targeted mechanism programmes we like to advance in Lundbeck. The orphan designation in Cushing’s syndrome for asedebart is also another example of a breakthrough innovation pipeline in neuroendocrine and rare disorders, where several programmes have been granted a number of special regulatory designations in recent years.” 

In the European Union, orphan designation is intended to support the development of medicines for rare, life-threatening or chronically debilitating diseases. Designated orphan medicines may benefit from incentives including protocol assistance, fee reductions and, if approved, ten years of market exclusivity for the designated indication8.9. 

References 

  1. Nieman LK. ACTH-Dependent Cushing Syndrome: Pathophysiology. Endocr Rev. 2022;43(2):117–171. 
  2. Fleseriu M, et al. Consensus on diagnosis and management of Cushing’s disease. Lancet Diabetes Endocrinol. 2021;9(12):847–875. 
  3. Nieman LK, et al. Treatment of Cushing’s Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015;100(8):2807–2831. 
  4. Lundbeck. Data on file. 
  5. Feldhaus AL, et al. Endocrinology. 2017;158(1):1–8. 
  6. Xing Y, et al. J Endocrinol. 2011;209(3):327–335. 
  7. European Medicines Agency. Orphan incentives. 
  8. European Medicines Agency. Market exclusivity for orphan medicines.