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Adrenal (Excluding Mineralocorticoids)

ORF32-07 - Crinecerfont Improves Weight-Related Outcomes and Insulin Resistance in Adults with Classic Congenital Adrenal Hyperplasia: 2-Year Results from the CAHtalyst™ Adult Study

Sunday, June 14, 2026
2:55 PM - 3:10 PM CT
Location: Room W184ABC
Disclosure(s):
Henrik Falhammar, MD, PhD, FRACP: Crinetics Pharmaceuticals: Clinical Trial Investigator (); Lundbeck: Clinical Trial Investigator (); Neurocrine Biosciences: Advisory Board (), Clinical Trial Investigator (), Speakers' Bureau (); Spruce Biosciences: Clinical Trial Investigator ()
Deborah P. Merke, MS, MD: No relevant disclosure to display



Background: In patients with classic congenital adrenal hyperplasia (CAH), long-term exposure to supraphysiologic glucocorticoid (GC) doses can lead to obesity and insulin resistance. 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 patients (≥4 years old) with classic CAH, including both salt-wasting and simple virilizing forms, thereby enabling GC dose reduction. This study evaluated outcomes related to body weight and insulin resistance (IR) in CAHtalyst™ Adult (NCT04490915) participants who received up to 2 years of crinecerfont.

Methods: Participants who completed the 24-week double-blind placebo-controlled period and the 6-month open-label period of CAHtalyst Adult continued taking crinecerfont in the ongoing open-label extension. Changes in body weight, body mass index (BMI), body composition, and homeostatic model assessment of IR (HOMA-IR) were analyzed at Month 12 and Month 24.

Results: The 182 randomized participants had a baseline mean daily GC dose of 17.6 mg/m2/d (32.3 mg/d) hydrocortisone equivalents (HCe). At baseline, mean body weight was 79.3 kg, mean BMI was 29.8 kg/m2 and 71% were overweight or obese (BMI ≥25 kg/m2); mean HOMA-IR was 3.2 and 42% had IR (HOMA-IR >2.5). GC dose decreased from baseline by a mean±SEM of -37±1% to 10.9±0.3 mg/m2/d (19.9±0.5 mg/d) HCe at Month 12; this reduction was maintained at Month 24 (-38±1%; 10.6±0.2 mg/m2/d [19.4±0.5 mg/d] HCe). In all participants, mean reductions from baseline in weight and BMI at Month 12 (-1.8±0.4 kg [-2.3±0.6%] and -0.7±0.2 kg/m2, respectively) were sustained at Month 24 (-1.8±0.6 kg [-2.1±0.7%] and -0.7±0.2 kg/m2, respectively). Sustained reductions in BMI were also observed in participants who were overweight or obese at baseline (Month 12, -0.9±0.2 kg/m2; Month 24, -0.9±0.3 kg/m2), and 31% (37/120) and 38% (39/103) of this subgroup achieved >5% reduction in weight at Months 12 and 24, respectively. At both time points, these participants had mean decreases in fat mass exceeding that in lean mass, with reductions of -1.5±0.5 kg vs -0.8±0.2 kg, respectively, at Month 12 and -1.6±0.7 kg vs -0.8±0.3 kg, respectively, at Month 24. Mean reductions from baseline in HOMA-IR were sustained from Month 12 and Month 24 in all participants overall (Month 12, -0.6±0.2; Month 24, -0.6±0.2) and in participants with IR at baseline (Month 12, -1.5±0.3; Month 24, -1.7±0.5). Crinecerfont was well tolerated, and no new safety signals were observed during long-term treatment.

Conclusion: Adults with CAH who received up to 2 years of crinecerfont achieved and maintained reductions in GC dose, accompanied by favorable changes in weight, body composition, and IR. These results suggest that crinecerfont can reduce the risk of cardiometabolic complications associated with long-term supraphysiologic GC treatment.