Guidance Published for Glucocorticoid Reduction With Crinecerfont in CAH

On May 6, 2026, Neurocrine Biosciences announced publication of 2 peer-reviewed expert recommendation papers outlining how clinicians may approach glucocorticoid dose reduction after starting crinecerfont in adults and children with classic congenital adrenal hyperplasia (CAH).1

The recommendations are presented separately for pediatric patients aged 4 to 17 years and for adults, reflecting different treatment goals and monitoring considerations across age groups. The publication addresses a practical issue left only partly answered by pivotal trial protocols: how to taper supraphysiologic glucocorticoid doses while maintaining cortisol replacement and monitoring for withdrawal or adrenal insufficiency.1

“In children and adolescents with classic congenital adrenal hyperplasia, treatment decisions must carefully balance disease control with normal growth and development,” Mimi Kim, MD, associate professor of clinical pediatrics at Keck School of Medicine, University of Southern California, said in a statement. “These recommendations provide clinicians with a structured, practical approach to glucocorticoid management that helps support growth, bone maturation, and pubertal development as CRENESSITY is incorporated into care.”1

What the new crinecerfont glucocorticoid-reduction recommendations include

According to the company announcement, the 2 manuscripts offer algorithm-based guidance derived from phase 3 trial experience and clinician experience in practice. For pediatric patients, the recommendations target glucocorticoid reduction toward the upper end of the physiologic range, cited as 8 to 11 mg/m2/day in hydrocortisone equivalents, with the broader physiologic range listed as 4 to 11 mg/m2/day.1 In adults, the target physiologic range is described as 2 to 14 mg/m2/day in hydrocortisone equivalents.1

Both papers emphasize gradual, supervised dose reductions rather than abrupt tapering, with ongoing assessment for symptoms of glucocorticoid withdrawal, adrenal insufficiency, and mineralocorticoid imbalance. Key biomarkers include androstenedione, testosterone, renin, and electrolytes, among others. The papers also note glucocorticoid reduction is not necessarily the goal for every patient; some may already be receiving physiologic replacement and may start crinecerfont primarily for androgen control.1

Classic CAH, most commonly due to 21-hydroxylase deficiency, has historically required glucocorticoid regimens that balance cortisol replacement with suppression of excess adrenocorticotropic hormone and adrenal androgen production.3 Endocrine Society guidance has long recognized the tradeoff between controlling hyperandrogenism and avoiding overtreatment with glucocorticoids, particularly in growing children.3

How phase 3 CAHtalyst data support the FDA-approved use of crinecerfont

Crinecerfont is an oral corticotropin-releasing factor type 1 receptor antagonist intended to reduce pituitary adrenocorticotropic hormone signaling and thereby decrease adrenal androgen production without adding glucocorticoid exposure. The US Food and Drug Administration (FDA) approved the drug in December 2024 for use with glucocorticoids to control androgens in classic CAH.1,2

The approval was supported by the phase 3 CAHtalyst program, which enrolled 285 patients across pediatric and adult studies. In the pediatric program, 103 participants aged 4 to 17 years first underwent 4 weeks of treatment to assess androgen control, followed by 24 additional weeks evaluating whether individualized glucocorticoid down-titration could be achieved while maintaining or improving androstenedione levels. In the adult study, 182 participants aged 18 to 58 years underwent a similar design, with 20 additional weeks assessing reduction of glucocorticoids into the physiologic range while maintaining or improving androstenedione. Open-label extension phases of both trials are ongoing.1

Safety considerations and unanswered questions for real-world implementation

The central safety concern during glucocorticoid reduction in CAH remains underreplacement, including adrenal insufficiency or adrenal crisis. The FDA label for crinecerfont warns of sudden adrenal insufficiency or adrenal crisis if patients receive too little glucocorticoid, and it states that glucocorticoid therapy should be continued during treatment. Common adverse effects listed in labeling include tiredness, headache, decreased appetite, and myalgia in adults, and headache, abdominal pain, fatigue, nasal congestion, and epistaxis in children.2

The expert papers may help fill an implementation gap as use expands, but several questions remain. The press release did not report long-term outcome data on growth, bone age normalization, fertility-related measures, cardiometabolic outcomes, or rates of adrenal crises under algorithm-guided tapering. Real-world uptake and consistency of biomarker-based monitoring also remain to be seen. For now, the newly published recommendations add age-specific structure to a treatment area where physiologic glucocorticoid replacement and androgen control have often been difficult to reconcile.1

References

1. Neurocrine Biosciences. Neurocrine Biosciences announces publication of expert recommendations for glucocorticoid dose reduction after initiating CRENESSITY (crinecerfont) for the treatment of classic congenital adrenal hyperplasia. Published May 06, 2026. Accessed May 06, 2026. https://neurocrine.gcs-web.com/news-releases/news-release-details/neurocrine-biosciences-announces-publication-expert
2. CRENESSITY (crinecerfont) prescribing information. Neurocrine Biosciences. Accessed May 06, 2026. https://edge.prnewswire.com/c/link/?t=0&l=en&o=4681537-1&h=2790446935&u=https%3A%2F%2Fc212.net%2Fc%2Flink%2F%3Ft%3D0%26l%3Den%26o%3D4325283-1%26h%3D3091277039%26u%3Dhttp%253A%252F%252Fwww.neurocrine.com%252Fcrenessitypi%26a%3DPrescribing%2BInformation&a=Prescribing+Information
3. Speiser PW, Arlt W, Auchus RJ, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(11):4043-4088. doi: 10.1210/jc.2018-01865