Crinecerfont Reduces Steroid Use for Pediatric CAH in Phase 3 Analysis

Exploratory analyses from the Phase 3 CAHtalyst Pediatric study revealed crinecerfont (CRENESSITY) reduced glucocorticoid dosing while maintaining or improving androstenedione levels in pediatric patients with classic congenital adrenal hyperplasia (CAH).1

Announced by Neurocrine Biosciences, Inc., on May 8, 2025, crinecerfont achieved similar benefits across all patient subgroups, irrespective of demographics or baseline hormone levels. These findings were presented at the 2025 Joint Congress of European Society for Paediatric Endocrinology and the European Society of Endocrinology.

“High-dose steroids are often accompanied by side effects and complications,” said Eiry W. Roberts, MD, chief medical officer of Neurocrine Biosciences. “By enabling patients to maintain or improve their androgen levels while reducing their reliance on high-dose glucocorticoids, [crinecerfont] has the potential to meaningfully enhance long-term outcomes, helping patients with both the hormonal imbalances that characterize CAH, as well as the challenges associated with chronic high-dose glucocorticoid treatment.”

Androstenedione overproduction in pediatric CAH has been linked to abnormal growth and development, premature puberty, and cognitive or behavioral developmental concerns. Historically, treatment strategies focused primarily on correcting endogenous cortisol deficiency with glucocorticoids, but the need for high doses has been associated with notable complications of steroid excess, including diabetes, cardiovascular disease, and osteoporosis.2

Crinecerfont is an oral corticotropin-releasing factor type 1 receptor (CRF1) antagonist targeting excess adrenocorticotropic hormone (ACTH) and adrenal androgens without relying solely on glucocorticoids. Addressing CRF1 receptors in the pituitary controls hormone levels and allows for lower doses of cortisol replacement therapy.1

The US Food and Drug Administration (FDA) approved crinecerfont for CAH in adults and children aged 4 years and older in December 2024, with availability as capsules (50 mg, 100 mg) or an oral solution (50 mg/mL). Approval was supported by positive data in the CAHtalyst Pediatric and Adult Phase 3 global registrational studies.3

These studies marked the largest interventional clinical trial program in classic CAH, involving 285 pediatric and adult patients with classic CAH due to 21-hydroxylase deficiency. In CAHtalyst Pediatric, 103 patients were randomly assigned to crinecerfont (n = 69) or placebo (n = 34) for 28 weeks, with a primary endpoint of the least-squares mean change from baseline in high levels of androstenedione (A4) at Week 4.1

Prespecified analyses of the primary endpoint and post-hoc subgroup analyses of glucocorticoid dose reduction at Week 28 were performed based on age, sex, race, region, body mass index (BMI), pubertal stage, and baseline A4, offering evaluation of the treatment effects across diverse patient characteristics.

These analyses found crinecerfont reduced glucocorticoid doses while maintaining or improving A4 levels across all subgroups. Compared with placebo, crinecerfont significantly reduced A4 levels from baseline (–6.9 vs. +2.5 nmol/L; least-squares mean difference, –9.3 nmol/L; P =.0002). Subgroup analyses at Week 4 were consistent with results across the overall population.

Crinecerfont also demonstrated a significant reduction in glucocorticoid doses from baseline at Week 38, while maintaining or improving A4 levels, compared with placebo (overall, –18.0% vs +5.6%; least-squares mean difference, –23.5%; P <.0001). Subgroup analyses once more remained consistent with the overall population.

Across the CAHtalyst Pediatric study, crinecerfont remained well-tolerated, with the most common adverse reactions (≥4%) being headache, abdominal pain, fatigue, nasal congestion, and nosebleed. In the release, Neurocrine Biosciences indicated crinecerfont’s ability to reduce glucocorticoid doses and maintain or improve androgen levels suggests the potential to benefit long-term patient outcomes.1

References

1. Neurocrine Biosciences announces new results from exploratory analyses of the phase 3 cahtalystTM pediatric study demonstrating CRENESSITYTM reduces glucocorticoid dosing while maintaining or improving androstenedione across patient subgroups. Neurocrine Biosciences. May 8, 2025. Accessed May 12, 2025. https://neurocrine.gcs-web.com/news-releases/news-release-details/neurocrine-biosciences-announces-new-results-exploratory.

2. Speiser PW, Azziz R, Baskin LS, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline [published correction appears in J Clin Endocrinol Metab. 2010 Nov;95(11):5137] [published correction appears in J Clin Endocrinol Metab. 2021 Jun 16;106(7):e2853. doi: 10.1210/clinem/dgab316.]. J Clin Endocrinol Metab. 2010;95(9):4133-4160. doi:10.1210/jc.2009-2631

3. Neurocrine Biosciences announces FDA approval of CRENESSITYTM (crinecerfont), a first-in-class treatment for children and adults with classic congenital adrenal hyperplasia. Neurocrine Biosciences. December 13, 2024. Accessed May 12, 2025. https://neurocrine.gcs-web.com/news-releases/news-release-details/neurocrine-biosciences-announces-fda-approval-crenessitytm.