FDA Approves Crinecerfont for Managing Classic Congenital Adrenal Hyperplasia in Adults and Children

On December 13, the FDA approved crinecerfont for use alongside glucocorticoids to manage androgen levels in adults and pediatric patients aged 4 years and older with classic congenital adrenal hyperplasia (CAH).

“Today’s approval provides an important advance for patients with classic congenital adrenal hyperplasia and highlights the FDA’s continued commitment to advancing effective and safe treatments for rare diseases,” Theresa Kehoe, MD, Director of the Division of General Endocrinology in the FDA’s Center for Drug Evaluation and Research, said in a press release. “The FDA will continue working with patients, drug companies and health care providers to address the unmet medical needs of the rare disease community.”

Classic CAH is a genetic disorder of the adrenal glands, which results in an inability to produce adequate cortisol, a hormone critical for stress response and metabolism. As a compensatory mechanism, the adrenal glands overproduce androgens (testosterone-like hormones), leading to a range of complications, including early puberty, growth disturbances, and fertility issues.

Patients with CAH typically require high doses of glucocorticoids to replace cortisol and suppress excess androgen production. Prolonged use of these high doses can result in significant side effects, such as bone loss, weight gain, and increased risk of infections, highlighting the urgent need for alternative treatments.

Crinecerfont is a non-steroidal corticotropin-releasing factor type 1 receptor antagonist. By reducing excessive adrenal androgen production, crinecerfont lowers the need for high doses of glucocorticoids, allowing for better hormonal balance with fewer side effects.

The approval of crinecerfont is based on data from two randomized, double-blind, placebo-controlled trials evaluating its safety and efficacy in 182 adults and 103 children with classic CAH. In the first trial, 122 adults received crinecerfont, and 60 received placebo twice daily for 24 weeks. After 4 weeks, glucocorticoid doses were tapered to replacement levels, with adjustments made to maintain androstenedione control. The results showed that participants receiving crinecerfont reduced their daily glucocorticoid dose by 27% while maintaining control of androstenedione levels. The placebo group achieved only a 10% reduction in glucocorticoid dose.

In the second trial, 69 children received crinecerfont, and 34 received placebo twice daily for 28 weeks. Serum androstenedione levels were measured at week 4, and glucocorticoid doses were adjusted accordingly. The results indicated that the crinecerfont group had a statistically significant reduction in androstenedione levels compared with an increase in the placebo group. At 28 weeks, patients taking crinecerfont reduced their glucocorticoid dose by 18%, while the placebo group required a 6% increase in glucocorticoid dose.

While crinecerfont is generally well-tolerated, it includes a warning for acute adrenal insufficiency or adrenal crisis. This can occur if patients do not receive adequate glucocorticoid replacement during stress-inducing situations (e.g., illness or surgery).

The commons side effects for adults were fatigue, dizziness, and joint pain, while the side effects for children were headache, abdominal pain, and fatigue.

Crinecerfont should not be used by individuals with hypersensitivity to the drug or its components. Concurrent use with drugs that activate enzymes metabolizing crinecerfont may decrease its effectiveness. Dosage adjustments are outlined in the prescribing information.

Reference
FDA Approves New Treatment for Congenital Adrenal Hyperplasia. US Food and Drug Administration. December 13, 2024. Accessed December 24, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-congenital-adrenal-hyperplasia