FDA approves Crenessity for treatment of classic congenital adrenal hyperplasia

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The FDA announced the approval of Crenessity (crinecerfont; Neurocrine Biosciences) for use alongside glucocorticoids to manage androgen levels in adults and children aged 4 years and older with classic congenital adrenal hyperplasia (CAH).¹

“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,” said Theresa Kehoe, MD, director of the Division of General Endocrinology in the FDA’s Center for Drug Evaluation and Research. “The FDA will continue working with patients, drug companies and health care providers to address the unmet medical needs of the rare disease community.”¹

Classic CAH, a rare genetic disorder, impairs the adrenal glands' ability to produce sufficient cortisol while causing overproduction of androgens, leading to hormonal imbalances. Current treatments involve high doses of glucocorticoids to both replace deficient cortisol and suppress excess androgen production.²

Crenessity offers a new mechanism of action by directly reducing excessive adrenal androgen production. This allows patients to use lower doses of glucocorticoids while maintaining hormonal control, potentially minimizing long-term side effects of high-dose steroid therapy.¹

Results highlight

The approval is supported by data from two randomized, double-blind, placebo-controlled trials involving 285 patients.¹

• In one trial with 182 adult participants, those receiving Crenessity twice daily achieved a 27% reduction in their glucocorticoid dose while maintaining control of androgen levels, compared to a 10% reduction in the placebo group.¹
• The second trial, focusing on 103 pediatric patients, showed a statistically significant reduction in serum androgen levels at week 4 for those taking Crenessity, alongside an 18% reduction in glucocorticoid doses by the study’s end.¹

Safety and usage

Crenessity comes with a warning for potential adrenal crisis in patients who do not receive adequate glucocorticoid replacement therapy during periods of increased cortisol demand. Additionally, it should not be used by individuals with hypersensitivity to its active ingredients.¹

Drug interactions and potential enzyme activity affecting Crenessity’s metabolism are also considerations, with specific dose adjustment guidelines outlined in the prescribing information. Common side effects reported include fatigue, dizziness, and joint pain in adults, and headache, abdominal pain, and fatigue in children.¹

Expedited approval

Crenessity’s approval process was accelerated through the FDA’s fast track, breakthrough therapy, orphan drug, and priority review designations, reflecting its potential to address an unmet medical need.¹

References:

_{1. FDA. FDA approves new treatment for congenital adrenal hyperplasia. U.S. Food and Drug Administration. December 13, 2024. Accessed December 13, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-congenital-adrenal-hyperplasia.}

_{2. Momodu II, Lee B, Singh G. Congenital Adrenal Hyperplasia. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448098/}