FDA

First-in-class therapy approved for classic congenital adrenal hyperplasia

December 17, 2024

Brand name: Crenessity

Generic name: crinecerfont

Manufacturer: Neurocrine Biosciences

Approval date: December 13, 2024

FDA approved Crenessity (crinecerfont), a corticotropin-releasing factor type 1 receptor antagonist, as adjunctive treatment to glucocorticoid replacement to control androgens in adults and pediatric patients ≥4 years of age with classic congenital adrenal hyperplasia (CAH).

Efficacy

Crenessity’s approval is based on two randomized, double-blind, placebo-controlled trials in 182 adults and 103 children with classic CAH.

CAHtalyst Study (NCT04490915)

In the first trial, 122 adults received Crenessity twice daily and 60 received placebo twice daily for 24 weeks. After the first four weeks of the trial, the glucocorticoid dose was reduced to replacement levels, then adjusted based on levels of androstenedione. The primary measure of efficacy was the change from baseline in the total glucocorticoid daily dose while maintaining androstenedione control at the end of the trial. The Crenessity group reduced their daily glucocorticoid dose by 27% while maintaining control of androstenedione levels, compared with a 10% daily glucocorticoid dose reduction in the placebo group.

CAHtalyst Pediatric Study (NCT04806451)

In the second trial, 69 pediatric patients received Crenessity twice daily and 34 received placebo twice daily for 28 weeks. The primary measure of efficacy was the change from baseline in serum androstenedione at week 4. The Crenessity group experienced a statistically significant reduction from baseline in serum androstenedione, compared with an average increase from baseline in the placebo group. At the end of the trial, patients assigned to Crenessity were able to reduce their daily glucocorticoid dose by 18% while maintaining control of androstenedione levels compared with an almost 6% daily glucocorticoid dose increase in patients assigned to placebo.

Safety

Crenessity has a warning for acute adrenal insufficiency or adrenal crisis, which can occur if patients with underlying adrenal insufficiency who don’t also receive adequate doses of glucocorticoid replacement therapy in situations associated with increased cortisol need (i.e., “stress dose steroids”).

The most common side effects of Crenessity in adults include fatigue, dizziness, and arthralgia (joint pain). For pediatric patients, the most common side effects are headache, abdominal pain, and fatigue.

Recommended dose

The recommended adult dose of Crenessity is 100 mg PO twice daily with a meal. Weight-based dosing recommendations are provided for pediatric patients. Glucocorticoid replacement therapy for adrenal insufficiency should be continued.

Sources:

FDA. (2024, December 13). FDA approves new treatment for congenital adrenal hyperplasia. [Press release]. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-congenital-adrenal-hyperplasia

Neurocrine Biosciences. (2024, December 13). Neurocrine Biosciences Announces FDA Approval of CRENESSITY (crinecerfont), a First-in-Class Treatment for Children and Adults With Classic Congenital Adrenal Hyperplasia. [Press release]. https://neurocrine.gcs-web.com/news-releases/news-release-details/neurocrine-biosciences-announces-fda-approval-crenessitytm

Neurocrine Biosciences: Crenessity (crinecerfont). [Package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761297s000lbl.pdf