Crinecerfont 2-Year Data Show Sustained Glucocorticoid Reduction in Classic CAH Adults

New 2-year data from the phase 3 CAHtalyst Adult study demonstrate that approximately 70% of adults with classic congenital adrenal hyperplasia (CAH) treated with crinecerfont (Crenessity) achieved and sustained glucocorticoid (GC) doses within the physiologic range while maintaining androgen control.

The open-label extension findings, presented at the American Association of Clinical Endocrinology (AACE) 2026 Annual Meeting, build on previously reported 1-year results and represent the longest interventional follow-up in a large CAH cohort to date, according to the April 22, 2026 announcement by Neurocrine Biosciences.

"These sequelae significantly impact quality of life and commonly develop with traditional CAH treatment regimens. The 2-year findings provide important information on the durable benefit of treatment with [crincerfront]. Providers can confidently incorporate this additional knowledge to guide their management of adult patients with CAH into the future,” said Richard J. Auchus, MD, PhD, professor of internal Medicine and pharmacology at the University of Michigan Medical School and principal investigator for the CAHtalyst Adult study.

CAHtalyst Trial Design and Key Findings

The CAHtalyst Adult study enrolled 182 patients aged 18 to 58 years with classic CAH due to 21-hydroxylase deficiency, which Neurocrine Biosciences purports makes it the largest interventional trial conducted in this population.

The randomized phase of the trial initially evaluated whether 4 weeks of crinecerfont treatment improved androgen control, followed by an additional 20 weeks assessing whether GC doses could be reduced to physiologic range while androstenedione levels were maintained or improved. All participants subsequently entered the open-label extension period from which the current 2-year data are drawn.²

At month 24, mean daily GC dose decreased from a baseline of 17.6 mg/m²/day hydrocortisone equivalents (HCe) to 10.6 mg/m²/day HCe, representing a 38% mean reduction that held steady from month 18 onward. Among the 149 participants with month-24 data, 103 (69%) achieved a physiologic GC dose, defined as 11 mg/m²/day HCe or less, compared with 0 of 182 patients at baseline.

Of note, 75% of the 20 patients originally receiving dexamethasone transitioned to a dexamethasone-free regimen. Additionally, 62% of patients taking more than 2 daily doses of hydrocortisone eliminated at least one dose. Investigators noted these reductions did not worsen androstenedione levels relative to baseline, suggesting lowering GC exposure was not achieved at the cost of adrenal androgen escape.¹

Long-term treatment was generally well tolerated, with greater than 80% study retention at two years and no new safety signals. The most common adverse effects previously reported in adults include fatigue, headache, dizziness, joint pain, back pain, decreased appetite, and muscle pain.³

Richard J. Auchus, MD, PhD, professor of internal medicine and pharmacology at the University of Michigan Medical School and principal investigator of the CAHtalyst Adult study, noted that "many years of supraphysiologic glucocorticoid exposure increase the risk for long-term health consequences, which include obesity, diabetes, reduced bone density and psychosocial struggles."¹

Drug Background

Crinecerfont is an oral, selective corticotropin-releasing factor type 1 receptor (CRF1) antagonist. By blocking CRF1 receptors in the anterior pituitary, the drug reduces ACTH secretion and downstream adrenal androgen production through a non-GC mechanism, thereby enabling GC dose reduction toward physiologic cortisol replacement levels.

The US Food and Drug Administration approved crinecerfont in December 2024 for use in combination with GCs to control androgen levels in adults and children aged 4 years and older with classic CAH, based on pivotal data from the CAHtalyst Adult and Pediatric phase 3 trials.^2,3

These 2-year findings derive from the open-label extension phase without a concurrent placebo comparator, limiting the ability to attribute all observed benefits solely to the drug. Long-term cardiometabolic and bone density outcomes have not yet been reported at the 2-year mark, though one-year cardiometabolic data were presented separately at AACE 2026. Neurocrine has indicated that additional 2-year data across clinical endpoints will be shared at upcoming medical meetings.¹

"These 2-year findings demonstrated that [crincerfront] provided durable androgen control while enabling meaningful reductions in glucocorticoid exposure," said Sanjay Keswani, MD, chief medical officer of Neurocrine Biosciences.¹ "Importantly, these reductions were sustained over time without new safety or tolerability concerns, supporting [crincerfront] as a long-term treatment option that advances the standard of care for people living with this complex condition."

References

1. Neurocrine Biosciences. Neurocrine Biosciences presents new two-year CRENESSITY (crinecerfont) data showing sustained glucocorticoid dose reductions while maintaining androgen control in adults with classic congenital adrenal hyperplasia. Press release. April 22, 2026. https://www.prnewswire.com/news-releases/neurocrine-biosciences-presents-new-two-year-crenessity-crinecerfont-data-showing-sustained-glucocorticoid-dose-reductions-while-maintaining-androgen-control-in-adults-with-classic-congenital-adrenal-hyperplasia-302749451.html

2. Auchus RJ, Hamidi O, Pivonello R, et al. Phase 3 Trial of Crinecerfont in Adult Congenital Adrenal Hyperplasia. N Engl J Med. 2024;391(6):504-514. doi:10.1056/NEJMoa2404656

3. U.S. Food and Drug Administration. FDA Approves New Treatment for Congenital Adrenal Hyperplasia. U.S. Food and Drug Administration. Published December 13, 2024. Accessed April 23, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-congenital-adrenal-hyperplasia