Classic Congenital Adrenal Hyperplasia Drug Candidate Receives Orphan Drug Status

Christina T. Loguidice

Recently, Neurocrine Biosciences announced that its proprietary corticotropin-releasing factor 1 (CRF) receptor antagonist NBI-77860 has been granted orphan drug status by the FDA for the treatment of classic congenital adrenal hyperplasia (CAH),1 a disease that comprises a group of autosomal recessive disorders that result in an enzyme deficiency that alters the production of adrenal steroids. Currently, exogenous corticosteroids are the standard of care for treating patients with classic CAH. This treatment is used to correct the cortisol deficiency and reduce the excessive adrenocorticotropic hormone (ACTH) levels and androgen excess. However, the dose and duration of steroid use required to suppress ACTH is well above the normal physiological level of cortisol, which can lead to metabolic syndrome, bone loss, growth impairment, and Cushing’s syndrome. NBI-77860 has the potential to prevent these and other severe complications associated with corticosteroid therapy.
NBI‑77860 is a potent selective nonpeptide CRF receptor antagonist that has been shown to decrease the release of ACTH, thereby decreasing the production of androgens and other adrenal steroids.1 By lowering ACTH levels, NBI‑77860 enables lower doses of exogenous corticosteroids to be administered, preventing the side effects associated with this therapy.
“We are very pleased that the FDA has granted NBI-77860 orphan status to treat congenital adrenal hyperplasia, a devastating disease that is a significant challenge for both clinicians and patients,” said Malcolm Lloyd-Smith, chief regulatory officer, Neurocrine Biosciences, in a company press release. “This status represents a significant regulatory milestone for the CAH program and underscores the importance of bringing a safe and effective CAH therapy to market,” he added.
NBI-77860 successfully completed a pilot clinical trial in adults with classic CAH and is now being investigated in the 1401 study.2 This study is an open-label, sequential cohort, single ascending dose pharmacokinetic/pharmacodynamic study assessing three doses of NBI-77860 in 15 adolescent female patients with classic CAH. The trial includes three cohorts, with each cohort receiving one dose of NBI-77860 at bedtime. Biomarker measurements include ACTH, androgen, cortisol, and 17-hydroxyprogesterone levels collected the morning after dosing. Study results are anticipated later this year.


1. Neurocrine Biosciences announces granting of orphan drug status for NBI-77860 in congenital adrenal hyperplasia [news release]. San Diego, CA: Neurocrine Biosciences; January 16, 2015. Accessed February 8, 2015.
2. Neurocrine Biosciences. NBI-77860 (verucerfont). Accessed February 8, 2015.

RDR Quick Facts: Classic Congenital Adrenal Hyperplasia:

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