San Diego-based Neurocrine Biosciences, Inc. announced that the US Food and Drug Administration (FDA) has granted orphan drug designation to its investigational congenital adrenal hyperplasia (CAH) drug.
The agency granted orphan status to NBI-77860, a proprietary corticotropin releasing factor 1 (CRF) receptor antagonist for treatment of CAH, a disease that affects about 20,000 to 30,000 people in the US. With orphan drug designation, Neurocrine Biosciences receives development and commercial incentives.
Classic CAH is a genetic disorder, which results in an enzyme deficiency altering the production of adrenal steroids. As a result of this deficiency, the adrenal glands have little to no cortisol biosynthesis resulting in a potentially life-threatening condition. Classic CAH can result in salt wasting, dehydration and eventually death when left untreated. Even with cortisol replacement, persistent elevation of ACTH from the pituitary gland results in excessive androgen levels leading to virilization of females including precocious puberty, menstrual irregularity, short stature, hirsutism, acne and fertility problems.
Currently, corticosteroids are the standard of care for classic CAH. They are used to correct the endogenous cortisol deficiency and reduce the excessive 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, and therefore common and serious side effects include metabolic syndrome, bone loss, growth impairment and Cushing’s syndrome.
Nuerocrine Biosciences’ NBI-77860 is a potent, selective non-peptide CRF receptor antagonist. Blocking CRF receptors at the pituitary has shown to decrease the release of ACTH, which in turn decreases the production of adrenal steroids including androgens, and potentially the symptoms associated with classic CAH. Lower ACTH levels would also reduce the amount of exogenous corticosteroid necessary for these patients avoiding the side effects that are associated with excessive steroid therapy. Neurocrine Biosciences recently initiated a Phase I/II single ascending dose pharmacokinetic/pharmacodynamics study, evaluating three doses of the drug. The study consists of 15 adolescent females with classic CAH. They will be split into three cohorts and each will receive one dose of the drug at bedtime. The study’s biomarker measurements include ACTH, 17-OHP, androgen, and cortisol levels collected the day after dosing.
“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 of Neurocrine Biosciences. “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. We look forward to the results from our recently initiated 1401 Study of adolescents with classic CAH, in 2015.”
Source: Neurocrine Biosciences, Inc.