Crinecerfont Lowers Elevated Hormone Markers in Adults With 21-Hydroxylase Deficiency Congenital Adrenal Hyperplasia

dc.contributor.authorAuchus, Richard J.
dc.contributor.authorSarafoglou, Kyriakie
dc.contributor.authorFechner, Patricia Y.
dc.contributor.authorVogiatzi, Maria G.
dc.contributor.authorImel, Erik A.
dc.contributor.authorDavis, Shanlee M.
dc.contributor.authorGiri, Nagdeep
dc.contributor.authorSturgeon, Julia
dc.contributor.authorRoberts, Eiry
dc.contributor.authorChan, Jean L.
dc.contributor.authorFarber, Robert H.
dc.contributor.departmentMedicine, School of Medicineen_US
dc.description.abstractContext: Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) is characterized by impaired cortisol synthesis and excess androgen production. Corticotropin-releasing factor type 1 receptor (CRF1R) antagonism may decrease adrenal androgen production. Objective: This work aimed to evaluate the safety, tolerability, and efficacy of crinecerfont (NBI-74788), a selective CRF1R antagonist, in 21OHD. Methods: This open-label, phase 2 study, with sequential cohort design (NCT03525886), took place in 6 centers in the United States. Participants included men and women, aged 18 to 50 years, with 21OHD. Interventions included 4 crinecerfont regimens, each administered orally for 14 consecutive days: 50 or 100 mg once daily at bedtime (cohorts 1 and 2, respectively); 100 mg once daily in the evening (cohort 3); and 100 mg twice daily (cohort 4). Participants could enroll in more than 1 cohort. Main outcomes included changes from baseline to day 14 in adrenocorticotropin (ACTH), 17-hydroxyprogesterone (17OHP), androstenedione, and testosterone. Results: Eighteen participants (11 women, 7 men) were enrolled: cohort 1 (n = 8), cohort 2 (n = 7), cohort 3 (n = 8), cohort 4 (n = 8). Mean age was 31 years; 94% were White. Median percent reductions were more than 60% for ACTH (-66%), 17OHP (-64%), and androstenedione (-64%) with crinecerfont 100 mg twice a day. In female participants, 73% (8/11) had a 50% or greater reduction in testosterone levels; male participants had median 26% to 65% decreases in androstenedione/testosterone ratios. Conclusion: Crinecerfont treatment for 14 days lowered ACTH and afforded clinically meaningful reductions of elevated 17OHP, androstenedione, testosterone (women), or androstenedione/testosterone ratio (men) in adults with 21OHD. Longer-term studies are required to evaluate the effects of crinecerfont on clinical end points of disordered steroidogenesis and glucocorticoid exposure in patients with 21OHD.en_US
dc.identifier.citationAuchus RJ, Sarafoglou K, Fechner PY, et al. Crinecerfont Lowers Elevated Hormone Markers in Adults With 21-Hydroxylase Deficiency Congenital Adrenal Hyperplasia. J Clin Endocrinol Metab. 2022;107(3):801-812. doi:10.1210/clinem/dgab749en_US
dc.publisherEndocrine Societyen_US
dc.relation.journalThe Journal of Clinical Endocrinology & Metabolismen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.subjectCongenital adrenal hyperplasiaen_US
dc.subject21-hydroxylase deficiencyen_US
dc.titleCrinecerfont Lowers Elevated Hormone Markers in Adults With 21-Hydroxylase Deficiency Congenital Adrenal Hyperplasiaen_US
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