Study Reveals Novel Drug in Reducing Corticosteroid Dependence for CAH Patients

Researchers at the U-M Medical School have found a new medicine, crinecerfont, that might help people with congenital adrenal hyperplasia (CAH) to take fewer corticosteroids.

The study was published in the New England Journal of Medicine.

People born with a common type of congenital adrenal hyperplasia don't have an enzyme in their adrenal glands that helps make certain hormones. These hormones, called cortisol and aldosterone, are important for dealing with stress and regulating blood pressure.

Because their bodies lack this enzyme, children with this condition end up making too many male hormones, known as androgens. This can cause them to grow up faster than usual and have short stature and trouble having children when they're adults.

Even a regular stomach bug can be dangerous for people with this condition. It can cause something called an adrenal crisis, which can lead to shock if not treated quickly. The go-to therapy for children and adults with CAH are high high-dose corticosteroids, which come with a host of side effects, including weight gain, diabetes, osteoporosis, and cognitive dysfunction.

In the study, adults with CAH were randomly assigned to take either crinecerfont or a placebo in addition to their usual corticosteroid treatment.

After one month, patients who took the drug showed a 50% decrease in the adrenal androgen androstenedione, while those on the placebo did not experience this reduction. In the second phase of the study, the dosage of glucocorticoid was gradually lowered for each group.

The group on crinecerfont was able to maintain a reduction in the adrenal hormone after 24 weeks with a glucocorticoid dose close to that naturally produced by the body.

“These patients are still cortisol deficient and thus will still need cortisol replacement, but with crinecerfont, they need much less and could be less likely to experience the longterm negative effects of current glucocorticoid dosing,” said Richard Auchus, lead author of the study.

Reference: Kyriakie Sarafoglou,Mimi S. Kim,Maya Lodish,Eric I. Felner,Laetitia Martinerie,Natalie J. Nokoff,María Clemente,Patricia Y. Fechner,Maria G. Vogiatzi,Phyllis W. Speiser,Richard J. Auchus, Chan; Phase 3 Trial of Crinecerfont in Pediatric Congenital Adrenal Hyperplasia, New England Journal of Medicine; doi:10.1056/NEJMoa2404655