Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia (CAH) refers to a group of genetic conditions that result in an enzyme deficiency that alters the production of adrenal hormones. Approximately 95% of CAH cases are caused by a mutation that leads to deficiency of the enzyme 21-hydroxylase. In classic CAH, severe deficiency of this enzyme leads to an inability of the adrenal glands to produce cortisol and, in approximately 75% of cases, aldosterone.

If left untreated, classic CAH can result in salt wasting, dehydration, and even death. Even with cortisol replacement, high levels of adrenocorticotropic hormone (ACTH) from the pituitary gland result in excess androgen production leading to virilization and menstrual irregularities in females. Both males and females with classic CAH can experience problems with growth and development in childhood including early puberty, short stature or height below genetic potential, and fertility problems in adulthood.

Classic CAH is estimated to affect up to approximately 30,000 people in the U.S. and 50,000 people in Europe.

There are currently no nonsteroidal treatments approved by the U.S. Food and Drug Administration (FDA) for classic CAH. Glucocorticoids, the current standard of care, are used to correct the endogenous cortisol deficiency and to try to reduce the high ACTH levels and androgen excess. However, the dose and duration of steroid use required to try to control androgen excess is generally well above the normal physiological level of cortisol, which can result in serious and common complications of steroid excess, including metabolic abnormalities, bone loss, growth impairment, and iatrogenic Cushing’s syndrome.

Crinecerfont: An Investigational Therapy for Classic Congenital Adrenal Hyperplasia

Crinecerfont is an investigational, oral, nonsteroidal, selective corticotropin-releasing factor type 1 (CRF1) receptor antagonist under evaluation for the treatment of classic CAH due to 21-hydroxylase deficiency (21-OHD). Blockade of CRF receptors in the pituitary has been shown to decrease ACTH levels, which in turn decreases the production of adrenal steroids, including androgens, and potentially the symptoms associated with classic CAH. Research suggests that lowering androgen levels could enable lower dosing of glucocorticoids and thus potentially reduce the long-term exposure to greater than normal glucocorticoid doses in patients with classic CAH.

Clinical Trials: Congenital Adrenal Hyperplasia

Neurocrine Biosciences completed a Phase 2 study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of crinecerfont in adult patients with classic congenital adrenal hyperplasia (CAH). The final results from this open-label, 14-day study evaluating multiple dosing regimens were reported in June 2020.

Neurocrine Biosciences is currently enrolling patients in global registrational studies of crinecerfont in adult (18 years and older) and pediatric (2 years to 17 years) patients with classic CAH. For more information about these Phase 3 clinical studies of crinecerfont, please visit CAHtalyst.CAHstudies.com, or ClinicalTrials.gov (adult study) and CAHtalystpeds.CAHstudies.com or ClinicalTrials.gov (pediatric study).

CAHtalog™ Registry: A New CAH Patient Registry

The CARES Foundation, partnering with Neurocrine Biosciences and PicnicHealth, has established the CAHtalog™ (Congenital Adrenal Hyperplasia: Patient and Clinical Outcomes in Real-World Practice Settings) Registry. The goal of the registry is to support patient-centered research that will enhance the scientific community’s foundational knowledge of CAH and ultimately improve the lives of patients who live with it every day. Participants can contribute to CAH research and share their unique patient journey and voice without the need for in-person visits. After enrollment, participants will have ready access to their digital medical records in one place. To learn more about the CAHtalog™ Registry and how to participate, click here.