ECEESPE2025 Rapid Communications Rapid Communications 13: Adrenal and Cardiovascular Endocrinology Part 2 (6 abstracts)
Crinecerfont improves reproductive hormones in classic congenital adrenal hyperplasia: 1-year results from the phase 3 CAHtalyst™ adult study
Deborah Merke 1,2 , Sonal Vaid 1 , Maamoun Salam 3 , Duarte Pignatelli 4 , Andrea Isidori 5 , Nicole Reisch 6 , Lee Ann Keener 1 , Thom Board 7 , Vivian Lin 7 , Robert Farber 7 , Eric Jen 7 , Julia Sturgeon 7 & Jean Chan 7
1National Institutes of Health Clinical Center, Bethesda, United States; 2Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States; 3Washington University School of Medicine, St. Louis, United States; 4Hospital S João, Universidade do Porto, Porto, Portugal; 5Sapienza University of Rome, Rome, Italy; 6Ludwig Maximilians Universität München, Medizinische Klinik IV, Munich, Germany; 7Neurocrine Biosciences, Inc., San Diego, United States
JOINT3318
Background: //tgcqGonadal dysfunction with classic congenital adrenal hyperplasia (CAH) is due to testicular adrenal rest tumors and/or poor hormonal control (males) and to high adrenal androgens and progesterone (P4) (females). Crinecerfont, a corticotropin releasing factor type 1 receptor (CRF1) antagonist, is FDA-approved for adjunctive treatment to glucocorticoid (GC) replacement to control androgens in patients with CAH. In CAHtalyst™ Adult (NCT04490915), least-squares mean (LSM) percent changes in GC dose at Week 24 (end of double-blind placebo-controlled period) indicated a significant reduction with crinecerfont (-27.3% vs -10.3% for placebo; LSM difference -17.0%; P <0.0001) while androstenedione (A4) was maintained/improved relative to Day 1 baseline (BL). At Month 12 (end of open-label period), mean percent decreases from BL were -24.6% in participants continuing crinecerfont (CFT/CFT) and -29.7% in those switching from placebo (PBO/CFT).
Objective: To evaluate reproductive hormone changes in adults with CAH who received up to 1 year of crinecerfont, in the context of substantial GC dose reductions.
Methods: Analyses conducted at Week 24 and Month 12 were as follows: luteinizing hormone (LH), follicle stimulating hormone (FSH), A4-to-testosterone ratio (A4/T) in males; testosterone (T) and P4 in females. Males included for analysis had abnormal (low or high) LH, abnormal FSH, or A4/T ≥0.5 at BL. Females had elevated T or P4 at BL, with analysis conducted without regard to menstrual cycle phase. In participants with abnormal values at BL, results are presented as % (n/N) (n=number achieving normalisation; n=number with available assessments).
Results: The percentages of males achieving normal/target levels at Week 24 with crinecerfont vs placebo were: LH (47.4% [9/19] vs 22.2% [2/9]); FSH (13.3% [2/15] vs 14.3% [1/7]); A4/T (18.9% [7/37] vs 4.5% [1/22]). Results at Month 12 for CFT/CFT and PBO/CFT were: LH (64.7% [11/17], 44.4% [4/9]); FSH (35.7% [5/14], 14.3% [1/7]); A4/T (23.5% [8/34], 23.8% [5/21]). The percentage of females achieving normal levels at Week 24 were: T (10.7% [3/28] vs 0% [0/11]; P4 (13.5% [5/37] vs 5.9% [1/17]). Results at Month 12 for CFT/CFT and PBO/CFT were: T (3.7% [1/27], 9.1% [1/11]); P4 (8.6% [3/35], 18.8% [3/16]).
Conclusion: Crinecerfont has been shown to reduce ACTH, androgens, and androgen precursors in paediatric and adult patients with CAH. These analyses from CAHtalyst Adult indicate potential normalisation of reproductive hormones with crinecerfont, even with substantial GC dose reductions. CRF1 antagonism may be a promising therapeutic approach for improving reproductive hormones in adults with CAH.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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