Crinecerfont Maintains Improvements in Pediatric CAH at 2 Years, With Patricia Fechner, MD

Pediatric patients with congenital adrenal hyperplasia (CAH) treated with crinecerfont have shown lower glucocorticoid doses and reduced symptoms, according to 2-year data from the CAHtalyst Pediatric study.1

“I think we are approaching a true tradeoff now,” Patricia Fechner, MD, attending physician at Seattle Children’s Hospital and a professor of pediatrics at the University of Washington School of Medicine, told HCPLive in an exclusive interview. “We no longer need to dose our glucocorticoids for treatment of CAH to suppress the adrenal androgens and to replace the adrenal insufficiency – we can separate those 2 mechanisms and just give the glucocorticoid dosing for adrenal insufficiency and then give the crinecerfont to maintain lower doses of adrenal androgens.”

The CAHtalyst Pediatric study is a randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of crinecerfont in children. It was conducted across 46 locations worldwide and included patients with a medically confirmed diagnosis of classic CAH due to 21-hydroxylase deficiency who were on a stable steroid regimen and had elevated androgen levels. Patients with any other forms of classic CAH, a history of bilateral adrenalectomy, hypopituitarism, or other conditions needed chronic glucocorticoid therapy, or a history of cancer, among other criteria, were excluded.2

Patients were randomly assigned in a 2:1 ratio to receive either crinecerfont as a solution or capsule, administered orally twice daily for 28 weeks or matching placebo. A stable glucocorticoid dose was maintained for 4 weeks, followed by an adjustment to 8 to 10 mg per square meter of body surface area per day, so long as androstenedione levels were controlled. Following the initial 28-week period, the placebo patients crossed over to crinecerfont for ≥24 weeks.2

The primary outcome was change from baseline in serum androstenedione at week 4, measured via blood serum samples. Secondary outcomes included change in serum 17-hydroxyprogesterone at week 4, percent change in glucocorticoid daily dose at week 28, and change from baseline in the ratio of bone age to chronological age at week 28.2,3

A total of 103 patients were randomized – 69 were assigned to crinecerfont and 34 to placebo. Of these, 100 (97%) remained in the trial at 28 weeks. The mean glucocorticoid dose at baseline was 16.4 mg per square meter per day, and the mean androstenedione level was 15 nmol/L. By week 4, investigators noted substantially reduced androstenedione in the crinecerfont group (-6.9 nmol/L) and a concurrent increase in the placebo group (2.5 nmol/L). By week 28, mean glucocorticoid had decreased by 18% with crinecerfont but increased by 5.6% in the placebo arm.3

The present 2-year data follow these trends, with patients continuing to experience significant reductions in adrenocorticotropic hormone and 17-hydroxyprogesterone while achieving lower glucocorticoid doses. The analysis included 86 patients who had completed 2 years of treatment in the open-label extension period. Meaningful reductions were observed across hormone control, excess androgens, and long-term supraphysiologic glucocorticoid exposure – in addition, treatment was well-tolerated, with >80% study retention by 2 years and no new safety signals.1

“This is the first new medication in over 70 years,” Fechner said. “It has changed how we treat CAH, and I think families wanted to be in the study. It was well tolerated, and patients’ parents were able to see the results of improvement in growth, their management of CAH, and the decrease in hydrocortisone dosing that their children needed.”

Editors’ Note: Fechner reports disclosures with Neurocrine Biosciences, Spruce Biosciences, and Neurocrine Ltd.

References

1. Neurocrine Biosciences. Neurocrine Biosciences Presents New Two-Year CRENISSITY (crinecerfont) Data Demonstrating Durable Hormone Control, Reduced Glucocorticoid Exposure and Meaningful Clinical Improvements in Pediatric Patients with Classic Congenital Adrenal Hyperplasia. PRNewswire. May 1, 2026. Accessed May 15, 2026. https://www.prnewswire.com/news-releases/neurocrine-biosciences-presents-new-two-year-crenessity-crinecerfont-data-demonstrating-durable-hormone-control-reduced-glucocorticoid-exposure-and-meaningful-clinical-improvements-in-pediatric-patients-with-classic-congenital-302759774.html

2. Neurocrine Biosciences. Global Safety and Efficacy Registration Study of Crinecerfont in Pediatric Participants With Classic Congenital Adrenal Hyperplasia (CAHtalyst Pediatric Study). ClinicalTrials.gov Identifier: NCT04806451. Updated February 5, 2025. Accessed May 15, 2026. https://clinicaltrials.gov/study/NCT04806451

3. Sarafoglou K, Kim MS, Lodish M, et al. Phase 3 trial of Crinecerfont in pediatric congenital adrenal hyperplasia. New England Journal of Medicine. 2024;391(6):493-503. doi:10.1056/nejmoa2404655