Crinecerfont Reduces Glucocorticoid Doses in CAH, With Richard Auchus, MD, PhD

Crinecerfont (Crenessity) has demonstrated substantial and sustained reductions in glucocorticoid doses among adults with classic congenital adrenal hyperplasia (CAH), according to 2-year data from the CAHtalyst Adult study.1

These data were presented at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2026 in Las Vegas, Nevada, by Richard Auchus, MD, PhD, professor of pharmacology and internal medicine at the University of Michigan.1

“Glucocorticoids are not a good thing to be taking chronically – yes, you need them to survive, but you don’t really need them overnight,” Auchus told HCPLive in an exclusive interview. “What crinecerfont did was allow us to reduce the dose and put it in a more physiological regime, front-loading it in the morning, allowing them to have a circadian rhythm, and maintaining disease control at a level that the endocrinologist in the trial felt was appropriate for that patient.”

Crinecerfont, a selective oral corticotropin-releasing factor type 1 receptor (CRF1) antagonist, functions by reducing and controlling excess adrenocorticotropic hormone and adrenal antigens. It was first approved by the US Food and Drug Administration (FDA) in December of 2024 for the treatment of CAH in conjunction with glucocorticoids among adults and children ≥4 years.2,3

CAHtalyst Adult was a randomized, double-blind, placebo-controlled phase 3 study evaluating crinecerfont in adults with classic CAH. It consisted of a 24-week randomized period during which patients were assigned to either crinecerfont or placebo, followed by 1 year of active treatment with crinecerfont. Patients were then given the option to participate in an open-label extension period, which is projected to last for roughly 3 years.4

Patients were eligible for the study if they had a medically confirmed CAH diagnosis due to 21-hydroxylase deficiency and were on a stable steroid regimen. Patients with a diagnosis of any other known form of classic CAH, a history of bilateral adrenalectomy, hypopituitarism, or other conditions requiring chronic glucocorticoid therapy, or a clinically significant unstable medical condition or chronic disease aside from CAH, among other criteria, were excluded from the trial.4

The present data highlights 2-year data from the open-label extension – by month 24, 69% of the participants (103/149) had achieved a physiologic glucocorticoid dose of ≤11 mg/m2/day of hydrocortisone equivalents. Additionally, many participants had eliminated nonphysiologic glucocorticoid types altogether. Among the patients initially taking dexamethasone (n = 20), 75% shifted to a dexamethasone-free regimen, while 62% (37/60) taking >2 doses of hydrocortisone per day were able to eliminate a dose.2

Auchus also highlighted the significant retention throughout the open-label extension: >80% of patients were still taking crinecerfont at 2 years with no new safety signals detected.2

“CAH is a chronic disease, and there’s a lot of disease burden for these patients,” Auchus said. “We want them to be able to just take their medicine and get on with their lives and not worry about things. I think that high retention rate tells you that people are on board with this system.”

Editors’ Note: Auchus reports disclosures with Adrenas Therapeutics, Corcept, Crinetics, Neurocrine Biosciences, Recordati, Astellas, and others.

References

1. Bancos I, Hamidi O, Kiefer F, et al. Adults With Classic Congenital Adrenal Hyperplasia Taking Crinecerfont Demonstrated Sustained Decreases in Glucocorticoid Doses: 2-Year Results from the CAHtalyst Adult Study. Presented at the American Association of Clinical Endocrinology Annual Meeting 2026, Las Vegas, NV. April 22-24, 2026.

2. Neurocrine Biosciences, Inc. 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. PRNewswire. April 22, 2026. Accessed April 24, 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

3. Iapoce C. FDA Approves Crinecerfont for Congenital Adrenal Hyperplasia. HCPLive. December 13, 2024. Accessed April 24, 2026. https://www.hcplive.com/view/fda-approves-crinecerfont-for-congenital-adrenal-hyperplasia

4. Neurocrine Biosciences. Global Safety and Efficacy Registration Study of Crinecerfont for Congenital Adrenal Hyperplasia (CAHtalyst). ClinicalTrials.gov Identifier: NCT04490915. Updated February 5, 2025. Accessed April 24, 2026. https://clinicaltrials.gov/study/NCT04490915