Work

SAT-442 Crinecerfont Enables Reduction of Glucocorticoid Doses While Maintaining or Improving Androstenedione in Pediatric Patients with Classic Congenital Adrenal Hyperplasia: Subgroup Analyses From the Phase 3 CAHtalyst™ Pediatric Study

Year: 2025

Type: article

Abstract: Disclosure: O. Lekarev: Consultant for Neurocrine Biosciences and Eton Pharmaceuticals; medical and scientific advisory board for CARES Foundation. A. Erkin-Cakmak: None. M.G. Vogiatzi: Research support and consulting for Neurocrine, Spruce, Crinetics and Adrenas. E.A. Imel: Received clinical trial research funds and consulted for Neurocrine Biosciences; received clinical trial research funds from Spruce. M. Clemente: None. R. Coutant: None. G.B. Rosales: Full-time employee of Neurocrine Biosciences, Inc. E. Roberts: Full-time employee of Neurocrine Biosciences, Inc. G.S. Jeha: Full-time employee of Neurocrine Biosciences, Inc. R.H. Farber: Full-time employee of Neurocrine Biosciences, Inc. J.L. Chan: 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 two phase 3 trials, crinecerfont significantly reduced excess adrenal androgens, enabling subsequent reductions in GC doses in pediatric and adult patients with CAH. Objective: To analyze changes in androstenedione (A4) levels and GC doses while maintaining or improving A4 in subgroups of participants from the CAHtalyst™ Pediatric study (NCT04806451) of crinecerfont. Methods: Children and adolescents with CAH were randomized 2:1 to double-blind treatment with crinecerfont (25, 50, or 100 mg BID based on weight) or placebo for 28 weeks. GC doses were kept stable for the first 4 weeks to evaluate the impact on androgens and then reduced to a target of 8-10 mg/m2/d in hydrocortisone equivalents (HCe) by Week 28 while maintaining or improving A4 relative to Day 1 baseline (BL). Least squares (LS) mean changes from BL in A4 (before morning GC dose) at Week 4 and in GC dose at Week 28 were analyzed in the overall population and in subgroups defined by: region (US, outside US); sex (male, female); race (white, non-white); age (<12, 12-17 years); weight at BL (<55, ≥55 kg); body mass index (BMI) at BL (<85th, ≥85th percentile); pubertal stage at BL (Tanner stages 1-2, stages 3-5); A4 at BL (≤ULN [upper limit of normal], >ULN); and GC dose at BL (<16, ≥16 mg/m2/d HCe, for GC change only). Results: The study included 103 participants (crinecerfont, n=69; placebo, n=34). The mean age (±SD) was 12.1±3.5 years and 51% (n=53) were male. Mean A4 at BL was 431±461 ng/dL; mean GC dose was 16.4±3.9 mg/m2/d HCe. At Week 4, A4 was significantly reduced with crinecerfont but increased with placebo (-197 vs. +71 ng/dL; LS mean difference [LSMD]: -268 ng/dL; P=0.0002 [primary endpoint]). LSMDs of the point estimates for A4 change at Week 4 favored crinecerfont over placebo in all subgroups. At Week 28, GC dose was significantly reduced with crinecerfont (while maintaining or improving A4) but increased with placebo (-18.0% vs. +5.6%; LSMD: -23.5%; P<0.0001 [key secondary endpoint]). LSMDs of the point estimates for percent change in GC dose at Week 28 favored crinecerfont over placebo in all subgroups. For both A4 and GC, subgroup analyses were consistent with the primary and key secondary endpoint results in the overall population. Conclusion: Crinecerfont was effective in enabling GC dose reductions while maintaining or improving A4 in pediatric patients with CAH across all subgroups analyzed. These results demonstrate that pediatric patients with CAH can derive the androgen-lowering and GC-lowering benefits of crinecerfont treatment regardless of region, sex, race, age, weight/BMI, pubertal stage, or pretreatment A4 level or GC dose. Presentation: Saturday, July 12, 2025

Source: Journal of the Endocrine Society

DOI: 10.1210/jendso/bvaf149.310