Ann Pharmacother. 2025 Dec 1:10600280251396594. doi: 10.1177/10600280251396594. Online ahead of print.
ABSTRACT
OBJECTIVE: To review the pharmacology, efficacy, and safety profile of crinecerfont as adjunctive therapy in treating classic congenital adrenal hyperplasia (CAH).
DATA SOURCES: A literature search was conducted in PubMed from January 2008 to August 2025. The relevant manuscripts, abstracts, and clinical trials (ClinivalTrials.gov) were reviewed. The keywords used were crinecerfont, CYP21A2, androstenedione, 17 hydroxyprogesterone, glucocorticoids, CAH, and clinical trials.
DATA EXTRACTION: All crinecerfont-related publications, abstracts, packet inserts, and clinical trials were reviewed.
DATA SYNTHESIS: Crinecerfont is a specific CRF1R antagonist used as adjunctive therapy to treat classic CAH. Crinecerfont led to over a 50% reduction in adrenocorticotropic hormone (ACTH) and 17OHP levels in both adult and pediatric participants during phase II trials. Testosterone levels decreased by 32% to 74% in adults and 61% to 76% in pediatric participants. In phase III trials, Crinecerfont reduced glucocorticoid doses by 27.3% in adults and 18% in pediatric participants (both P < 0.001). In general, crinecerfont is well tolerated with adverse effects that are mild to moderate.Relevance to patient care and clinical practice in comparison to existing drugs:Crinecerfont is an orphan drug used as adjunctive therapy for patients with classic CAH. It can effectively decrease supraphysiological levels of glucocorticoids and control androstenedione levels, thereby reducing complications related to supraphysiological glucocorticoids in classic CAH.
CONCLUSION: Crinecerfont is the first approved adjunctive therapy for classic CAH that effectively decreases supraphysiological glucocorticoids levels and associated symptoms.
PMID:41321281 | DOI:10.1177/10600280251396594
