SUN-441 Crinecerfont Shows Favorable Trends in Improving Clinical Outcomes in Children and Adolescents With Classic Congenital Adrenal Hyperplasia: 1-Year Results From the CAHtalyst™ Pediatric Study

Abstract Disclosure: K. Sarafoglou: Research support from Office of Orphan Products Development of the Food and Drug Administration (R01FDR0006100), NIH-NCATS (UL1TR002494), NIH NINDS (U54NS115198), Neurocrine Biosciences, Inc, Spruce Biosciences, Crinetics Pharmaceuticals, Adrenas Therapeutics (BridgeBio), Alexion Pharmaceuticals, and BioMarin Pharmaceutical, Consultant for Novo Nordisk, Eton Pharmaceuticals, Neurocrine Biosciences, Spruce Biosciences, and Crinetics Pharmaceuticals on behalf of the University of Minnesota Medical School. O. Lekarev: Consultant for Neurocrine Biosciences, Inc, and Eton Pharmaceuticals, Medical and scientific advisory board for CARES Foundation. K. Loechner: None. M. Yang: Consulted for Eton pharmaceuticals. G.J. Mick: None. M.T. Dattani: Lecturing fees from Meck Serono, Pfizer, Novo Nordisk, Sandoz, Advisory Boards with Pfizer, Novo Nordisk, Consultancy for Sandoz, Pfizer, Besins. M. Bettendorf: None. M. Clemente: None. M. Salerno: None. R.H. Farber: Full-time employee of Neurocrine Biosciences, Inc. J.L. Chan: Full-time employee of Neurocrine Biosciences, Inc. G.B. Rosales: Full-time employee of Neurocrine Biosciences, Inc. G.S. Jeha: Full-time employee of Neurocrine Biosciences, Inc. Background: Crinecerfont, a corticotropin releasing factor type 1 receptor (CRF1) antagonist, is a first-in-class medication that is FDA-approved for adjunctive treatment to glucocorticoid (GC) replacement to control androgens in patients with classic congenital adrenal hyperplasia (CAH). In the Phase 3 CAHtalyst™ Pediatric study (NCT04806451), crinecerfont significantly reduced androgens in patients with CAH, enabling GC dose reductions from Day 1 baseline at the end of double-blind placebo-controlled (DBPC) treatment at Week 28, with a least squares (LS) mean percent change of -18.0% vs +5.6% for placebo (LS mean difference [LSMD] -23.5%, P<0.0001). At the end of open-label (OL) treatment at Week 52, mean percent decreases from BL in GC dose were -17.3% in participants who continued on crinecerfont (CFT/CFT) and -6.1% in those who switched from placebo (PBO/CFT). Objective: To evaluate clinical outcomes in children and adolescents with CAH who received up to 1 year of crinecerfont, in the context of substantial GC dose reductions. Methods: Outcomes related to ACTH/androgen excess (e.g., hirsutism in female participants) and GC exposure (e.g., body mass index standard deviation score [BMI SDS], insulin resistance, hyperlipidemia) were analyzed at the end of DBPC treatment (Week 28) and the end of OL treatment (Week 52). DBPC outcomes with p-values are presented as LS mean changes with LSMD. Results: In female participants, mean hirsutism visual analog scale scores (out of 0 [no symptoms] to 100 [very severe symptoms]) were 13.7 (crinecerfont) and 21.6 (placebo) at Day 1 baseline, and the changes from baseline were as follows: Week 28 (-7.0 vs +2.3 [crinecerfont vs placebo], LSMD -9.3, P=0.0251); Week 52 (-3.2 CFT/CFT, +1.9 PBO/CFT). Mean BMI SDS was elevated at baseline (1.2 crinecerfont, 1.1 placebo), and the changes from baseline were as follows: Week 28 (-0.09 vs +0.04 for placebo, LSMD -0.13, P=0.0493); Week 52 (-0.09 CFT/CFT, -0.02 PBO/CFT). Mean homeostatic model assessment of insulin resistance values were high at baseline (2.8 crinecerfont, 3.3 placebo), and the changes from baseline were as follows: Week 28 (-0.63 vs +0.27 for placebo, LSMD -0.90, P=0.0473); Week 52 (-0.72 CFT/CFT, -1.3 PBO/CFT). Mean values for cholesterol (total, LDL, and HDL) and triglycerides were within normal range at baseline and remained stable. Conclusion: Children and adolescents with CAH who received up to 1 year of crinecerfont showed improvements in BMI and insulin resistance. Hirsutism in female participants improved with crinecerfont, despite substantial reductions in GC dose. Given the known adverse effects of androgen excess and GC exposure, these results represent a promising therapeutic advancement in CAH. Presentation: Sunday, July 13, 2025