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Credit: US Food and Drug Administration The US Food and Drug Administration (FDA) has approved Neurocrine Biosciences’ crinecerfont (Crenessity), a new treatment to be used in conjuction with glucocorticoids for congenital adrenal hyperplasia (CAH) in adults and children aged 4 years and older. 1 Announced on December 13, 2024, the approval was awarded based on two randomized, double-blind, placebo-controlled trials in which individuals who received crinecerfont reduced their daily glucocorticoid dose and maintained control of androstenedione levels “Today’s approval provides an important advance for patients with classic CAH and highlights the FDA’s continued commitment to advancing effective and safe treatments for rare diseases,” Thereresa Kehoe, MD, director of the division of general endocrinology in the FDA’s Center for Drug Evaluation and Research, said in a statement. A rare genetic condition, classic CAH can impact the adrenal glands, wherein patients do not produce enough cortisol and produce excess androgens.
2 These individuals require high doses of glucocorticoids to lower these excess levels. Crinecerfont reduces excess adrenal androgen production, reducing the amount of required glucocorticoid treatment. Two randomized, double-blind, placebo-controlled trials evaluated crinecerfont in 182 adults and 103 children with classic CAH.
1 In the first trial, 122 received twice-daily crinecerfont and 60 received twice-daily placebo for 24 weeks. After the first 4 weeks, glucocorticoid doses were reduced to replacement levels and adjusted based on androstenedione levels. The trial’s primary efficacy endpoint was the change from baseline in the total glucocorticoid daily dose, with maintenance of androstenedione control, at the end of the trial.
Upon analysis, those who received crinecerfont reduced daily glucocorticoid doses by 27% and maintained control of androstenedione levels, compared with a 10% daily glucocorticoid dose reduction in the placebo cohort. For the second trial, 69 children and adolescents received twice-daily crinecerfont and 34 received twice-daily placebo for 28 weeks. The primary efficacy measure was the change from baseline in serum androstenedione at Week 4.
Analysis showed those who received crinecerfont demonstrated a statistically significant reduction from baseline in serum androstenedione, compared with an average increase from baseline in the placebo group. By the end of the trial, those receiving crinecerfont reduced their daily glucocorticoid dose by 18% and maintained control of androstenedione levels—on the other hand, the placebo cohort experienced an approximate 6% daily glucocorticoid dose increase. The drug has a warning regarding acute adrenal insufficiency or adrenal crisis, in the case of a patient with underlying adrenal insufficiency who does not receive adequate doses of glucocorticoid replacement therapy in situations linked to an increased cortisol need.
The FDA warned crinecerfont should not be taken by patients with hypersensitivity to the drug’s active ingredient or any its components. Safety outcomes showed the most common adverse effects of crinecerfont in adults included fatigue, dizziness, and arthralgia, while pediatric patients experienced headache, abdominal pain, and fatigue. The FDA previously granted crinecerfont Fast Track, Breakthrough Therapy, Orphan Drug and Priority Review designations.
3 “The FDA will continue working with patients, drug companies and health care providers to address the unmet medical needs of the rare disease community,” Kehoe added. 1 References 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. 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/ Neurocrine Biosciences announces U.
S. FDA accepts New Drug Applications and grants priority review for Crinecerfont for pediatric and adult patients with CAH. Neurocrine Biosciences.
July 1, 2024. Accessed December 13, 2024. https://neurocrine.
gcs-web.com/news-releases/news-release-details/neurocrine-biosciences-announces-us-fda-accepts-new-drug-0..
