MON-459 Crinecerfont Shows Favorable Trends in Improving Weight-Related Outcomes in Pediatric Patients With Classic Congenital Adrenal Hyperplasia: 1-Year Results from the CAHtalyst™ Pediatric Study

Abstract Disclosure: N. Nokoff: Consultant for Neurocrine Biosciences and expert panel member for World Athletics. M. Vogiatzi: Research support and consultingfor Neurocrine, Spruce, Crinetics and Adrenas. M.T. Dattani: Lecturing fees from Meck Serono, Pfizer, Novo Nordisk, Sandoz, Advisory Boards for Pfizer, Novo Nordisk, Consultant for Sandoz, Pfizer, Besins. G.S. Jeha: Full-time employee of Neurocrine Biosciences, Inc. G.B. Rosales: Full-time employee of Neurocrine Biosciences, Inc. J.L. Chan: Full-time employee of Neurocrine Biosciences, Inc. Background: In patients with classic congenital adrenal hyperplasia (CAH), chronic glucocorticoid (GC) treatment often leads to weight gain or obesity. Crinecerfont, a corticotropin releasing factor type 1 receptor antagonist, is a first-in-class medication that is FDA-approved for adjunctive treatment to GC replacement to control androgens in patients with CAH. In CAHtalyst™ Pediatric (NCT04806451), least-squares mean (LSM) percent changes in GC dose at Week 28 (end of double-blind placebo-controlled [DBPC] period) indicated a significant reduction with crinecerfont (-18.0% vs +5.6% for placebo; LSM difference [LSMD] -23.5%, P<0.0001) while androstenedione was maintained or improved relative to Day 1 baseline (BL). At Week 52 (end of open-label [OL] period), mean percent decreases from BL in GC dose were -17.3% in participants continuing crinecerfont (CFT/CFT) and -6.1% in those switched from placebo (PBO/CFT). Objective: To evaluate weight-related outcomes in pediatric patients with CAH who received up to 1 year of crinecerfont. Methods: Mean changes from BL in body mass index (BMI) standard deviation score (SDS) were analyzed at Weeks 28 and 52. In participants who were overweight or obese at BL (BMI ≥85th percentile), analyses included achievement of ≥0.15 reduction in BMI SDS and achievement of normal BMI. These responder analyses, assessed at Weeks 28 and 52, are presented as percentage (n/N) of participants, with n=number of responders and N=number with available data. Results: Mean BMI SDS at BL was 1.20 (crinecerfont) and 1.12 (placebo), and >50% of participants were overweight or obese (58.0% [40/69] crinecerfont, 58.8% [20/34] placebo). At Week 28, LS mean BMI SDS was reduced from BL with crinecerfont compared to an increase with placebo (-0.09 vs +0.04; LSMD: -0.13, P=0.0493). At Week 52, mean reductions from BL in BMI SDS were maintained with crinecerfont (-0.09 CFT/CFT, -0.02 PBO/CFT). Among participants who were overweight or obese at BL, a higher percentage achieved ≥0.15 reduction from BL in BMI SDS at Week 28 with crinecerfont (17.5% [7/40]) versus placebo (10.5% [2/19]). At Week 52, 32.4% (12/37) and 26.3% (5/19) achieved this threshold in the CFT/CFT and PBO/CFT groups, respectively. Achievement of normal BMI at Week 28 was also higher with crinecerfont (12.5% [5/40]) than placebo (5.3% [1/19]. At Week 52, 13.5% (5/37) and 10.5% (2/19) achieved normal BMI in the CFT/CFT and PBO/CFT groups, respectively. Conclusion: Children and adolescents with CAH who received up to 1 year of crinecerfont showed reductions in BMI SDS. Moreover, one-third of participants who were overweight or obese at baseline achieved a ≥0.15 reduction in BMI SDS with crinecerfont, and 13% achieved normal BMI. These analyses indicate that the GC dose reductions enabled by crinecerfont can allow for improvements in the weight-related effects associated with chronic supraphysiologic GC exposure. Presentation: Monday, July 14, 2025