OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Crinecerfont – Crenessity®

DRUG CLASS

Genetic Disorder Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Crinecerfont	752253-39-7	C27-H28-ClFN2-OS

ANNOTATED BIBLIOGRAPHY

References updated: 17 February 2025

• Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.

  (Expert review of hepatotoxicity published in 1999, before the availability of crinecerfont).
• Schimmer BP, Funder JW. Adrenocorticotropic hormone, adrenal steroids, and the adrenal cortex. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 845-861.

  (Textbook of pharmacology and therapeutics).
• FDA: Integrated Review. 2024. https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2025/218808Orig1s000,218820Orig1s000IntegratedR​.pdf

  (FDA website with product labels and the FDA review of data on its efficacy and safety of crinecerfont submitted by the sponsor in support of its approval as therapy of congenital adrenal hyperplasia, mentions that crinecerfont caused liver enlargement in rodents, but that in two registration trials, elevations in ALT, AST, and alkaline phosphatase were uncommon and no more frequent than with placebo; no patient developed ALT elevations above 3 times ULN and there were no cases of ALT elevations with jaundice)
• Merke DP, Auchus RJ. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. N Engl J Med. 2020;383:1248-1261. [PubMed: 32966723]

  (Review of the epidemiology, clinical features, complications, etiology, genetics, and management of congenital adrenal hyperplasia, the classical form of which is caused by 21-hydroylase deficiency, a P450 enzyme that is responsible for synthesis of cortisol and aldosterone, for which all newborns in the U.S. are screened at birth, and is fatal if untreated with glucocorticoids and sometimes with mineralocorticoids as well, but is still marked by complications of the excess androgen production).
• Newfield RS, Sarafoglou K, Fechner PY, Nokoff NJ, Auchus RJ, Vogiatzi MG, Jeha GS, et al. Crinecerfont, a CRF1 receptor antagonist, lowers adrenal androgens in adolescents with congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2023;108:2871-2878. [PMC free article: PMC10583973] [PubMed: 37216921]

  (Among 8 adolescents with congenital adrenal hyperplasia treated with crinecerfont [50 mg twice daily for 14 days], serum ACTH, 17-hydroxyprogesterone, and androstenedione levels decreased, while adverse events were mostly mild headache and dizziness and “no clinically significant findings were observed in routine laboratory tests”).
• Chrousos GP. Crinecerfont in a first clinical application of a CRH antagonist: further potential uses are still an open chapter! J Clin Endocrinol Metab. 2024;109:e1365-e1366. [PubMed: 37650613]

  (History of search for an inhibitor of corticotropin releasing hormone [CRF] for stress related disorders and the ultimate development of crinecerfont as therapy for the elevated levels of CRF in congenital adrenal hyperplasia).
• Sarafoglou K, Kim MS, Lodish M, Felner EI, Martinerie L, Nokoff NJ, Clemente M, et al.; CAHtalyst Pediatric Trial Investigators. Phase 3 trial of crinecerfont in pediatric congenital adrenal hyperplasia. N Engl J Med. 2024;391:493-503. [PubMed: 38828945]

  (Among 103 children or adolescents with congenital adrenal hyperplasia treated with crinecerfont for 28 weeks, androstenedione levels decreased by week 4 and were maintained while glucocorticoid doses were reduced by 18%, having increased by 6% with placebo, and there were no hepatic adverse events and “no evident safety concerns related to …clinical laboratory values”).
• Auchus RJ, Hamidi O, Pivonello R, Bancos I, Russo G, Witchel SF, Isidori AM, et al.; CAHtalyst Adult Trial Investigators. Phase 3 trial of crinecerfont in adult congenital adrenal hyperplasia. N Engl J Med. 2024;391:504-514. [PMC free article: PMC11309900] [PubMed: 38828955]

  (Among 182 adults with congenital adrenal hyperplasia treated with crinecerfont or placebo for 24 weeks, androstenedione levels changed by -299 vs +46 ng/dL with placebo, and glucocorticoid doses were reduced by 27% vs 10%, while fatigue and headache were the most common adverse events and “no safety concerns regarding crinecerfont were reported with respect to … clinical laboratory values”).