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Adrenal (Excluding Mineralocorticoids)

SUN-468 - Bone Outcomes in Adults with Classic Congenital Adrenal Hyperplasia Treated with Crinecerfont for Up to 2 Years in Cahtalyst™ Adult Study

Sunday, June 14, 2026
9:00 AM - 4:00 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
Henrik Falhammar, MD, PhD, FRACP, Associate Professor: Crinetics Pharmaceuticals: Clinical Trial Investigator (); Lundbeck: Clinical Trial Investigator (); Neurocrine Biosciences: Advisory Board (), Clinical Trial Investigator (), Speakers' Bureau (); Spruce Biosciences: Clinical Trial Investigator ()
Erik A. Imel, MD: Amgen Inc.: Advisory Board (), Clinical Trial Investigator (); Calcilytix: Clinical Trial Investigator (); Kyowa Kirin: Advisory Board (), Clinical Trial Investigator (), Consultant (); Neurocrine: Advisory Board (), Clinical Trial Investigator (); UltraGenyx: Advisory Board (), Clinical Trial Investigator (), Consultant ()


Background: Chronic exposure to supraphysiologic glucocorticoid (GC) doses in patients with classic congenital adrenal hyperplasia (CAH) can reduce bone mineral density (BMD), leading to increased fracture risk. Crinecerfont is a first-in-class corticotropin-releasing factor type 1 receptor antagonist that is FDA-approved as an adjunct to GC replacement to control androgens in classic CAH. A mean GC reduction of 38% was demonstrated after up to 2 years of treatment with crinecerfont in the Phase 3 CAHtalyst™ Adult trial (NCT04490915). These analyses evaluate the 2-year changes in BMD and bone turnover markers in CAHtalyst Adult participants.

Methods: Adult participants who completed the 24-week double-blind, placebo-controlled and 6-month open-label study periods continued taking crinecerfont in an ongoing open-label extension. Mean changes from baseline (CFB) were assessed in bone turnover markers (at Months 12 and 18) and BMD z-scores in the lumbar spine (L1-L4) and total hip (at Months 12, 18, and 24).

Results: At baseline, the 182 randomized participants had a median age of 29.5 years (range: 18-58) and mean GC dose of 17.6 mg/m2/d (32.3 mg/d) hydrocortisone equivalents; mean (±SD) BMD z-scores were below 0 (lumbar spine, -0.29±1.4; hip, -0.21±1.1). Mean levels of bone turnover markers at baseline were: serum bone-specific alkaline phosphatase (BAP; 11.9±4.9 µg/L), osteocalcin (23.9±11.9 µg/L), C-terminal telopeptide (CTx; 545.9±286.7 ng/L), urine N-terminal telopeptide/creatinine (NTx; 57.1±35.2 nmol bone collagen equivalents [BCE]/mmol creatinine). At Month 12, all 4 bone turnover markers had mean [95% CI] increases from baseline (BAP, 1.7 [1.2, 2.3] µg/L; osteocalcin, 6.6 [5.2, 7.9] µg/L; CTx, 86.3 [48.1, 124.6] ng/L; NTx, 10.6 [5.5, 15.7] nmol BCE/mmol creatinine). At Month 18, mean increases were sustained for bone formation markers (BAP, 1.5 [1.0, 2.0] µg/L; osteocalcin, 5.6 [4.0, 7.1] µg/L), though elevations in bone resorption markers lessened (CTx, 53.5 [16.3, 90.7] ng/L; NTx, 5.9 [0.9, 10.9] nmol BCE/mmol creatinine). For BMD z-scores, trends toward incremental improvement from baseline were seen at Month 12 (mean [95% CI] CFB: lumbar spine, 0.10 [0.05, 0.14]; hip, 0.03 [0.00, 0.06]), Month 18 (lumbar spine, 0.15 [0.09, 0.20]; hip, 0.04 [0.01, 0.08]), and Month 24 (lumbar spine, 0.17 [0.12, 0.23]; hip, 0.05 [0.01, 0.09]).

Conclusion: Adults with CAH who received up to 2 years of crinecerfont had a mean 38% reduction in observed GC dose. All bone turnover markers trended towards improvement from baseline to Month 12. Markers of bone formation remained at similar levels at Month 18 while markers of bone resorption (CTx, NTx) showed a decreasing trend. In addition, BMD z-scores in the lumbar spine and hip trended towards incremental improvement over time. These results suggest that the reduction in GC dose enabled by crinecerfont may improve bone health in patients with CAH.

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