Crinecerfont Shows Lasting Efficacy in Treating Adult CAH, with Richard Auchus, MD, PhD

According to a presentation by Richard Auchus, MD, PhD, professor of endocrinology and internal medicine at the University of Michigan Health, 1-year data from the phase 3 CAHtalyst adult trial displays the efficacy of crinecerfont (CRENESSITY) in treating patients with congenital adrenal hyperplasia (CAH). Auchus sat down with HCPLive to discuss the team’s findings and the possible future implementation of crinecerfont on a broad scale.

Previously approved by the US Food and Drug Administration (FDA) in December 2024 to treat CAH in conjunction with glucocorticoids, crinecerfont functions by reducing excessive production of adrenal androgen, which reduces the amount of glucocorticoid treatment necessary to return patients to equilibrium.1

The 24-week, double-blind, placebo-controlled trial compared patients with classic CAH on supraphysiologic glucocorticoid (GC) doses who were randomized in a 2:1 ratio to either crinecerfont or placebo. This was followed by a 24-week open-label period in which all participants received crinecerfont. GC doses were kept stable for the first 4 weeks of both periods and decreased as tolerated toward more physiologic levels while maintaining or improving androstenedione relative to baseline.2

A total of 182 adult patients were included, ranging from 18-58 years of age. Patients receiving consistent crinecerfont saw a -27.3% change in glucocorticoid doses, compared to -10.3% in the placebo group (least-squares mean difference, -17 percentage points; P <.001). At week 4, androstenedione levels decreased with crinecerfont (-299 ng/dL) but increased with placebo (45.5 ng/dL) (least-squares mean difference, -345 ng/dL; P <.001).3

The presented data concerned the second 24-week period, examining the placebo patients as they were crossed over to crinecerfont. Auchus explained these outcomes, highlighting similar reductions in glucocorticoid dosing.

“The clinical pearl from this is that they had their glucocorticoid dose reduced once a month, much more slowly than every 2 weeks that we reduced it in the crinecerfront group,” Auchus told HCPLive. “I think the important point is that when using the drug clinically, you should add the crinecerfont, you should wait until the labs are under control, and then you should very slowly taper the glucocorticoid dose as you would, for example, in someone with Cushing’s disease that has just been cured with surgery.”

Auchus also noted a significantly lower number of side effects in the crossed-over cohort than the crinecerfont cohort, largely those associated with glucocorticoid withdrawal such as headaches and fatigue.

Discussing alternative measurement methods, Auchus highlighted increases in bone turnover markers, noting small but significant improvements in bone density.

“Both turnover markers went up, interestingly, in both the placebo group and the crinecerfont group, but more in the latter, who had their glucocorticoid dose lowered further,” Auchus said. “There were some small but not statistically significant improvements in bone density at year one. So, I think that is a positive effect on bones, or at least a reduction of the negative effect on bones that the glucocorticoid therapy is giving these people.”

Auchus ultimately provided advice for clinicians, indicating the importance of patience and calling for more endocrinologists need to provide care for patients with CAH.

“A lot of adult endocrinologists don’t like taking care of this disease because it’s very hard: you either know that you’re doing damage to these patients by giving them a lot of glucocorticoid, or you know that they’re reducing the glucocorticoid to something physiological, but you’re letting their androgens rise and you say that there’s nothing we can do about that,” Auchus said. “My hope is that this makes it easy for any adult endocrinologist to transition a patient from the pediatric endocrinologist in good control with or without crinecerfont and then manage them for many decades, without a lot of angst and worry about concomitant comorbidities.”

Editors' Note: Auchus reports disclosures with Adrenas Therapeutics, Corcept Therapeutics, Neurocrine Biosciences, Novo Nordisk, Recordati Rare Diseases, Sparrow Pharmaceuticals, and others.

References

1. US Food and Drug Administration. FDA Approves New Treatment for Congenital AdrenalHyperplasia. December 13, 2024. Accessed July 21, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-congenital-adrenal-hyperplasia

2. Neurocrine Biosciences. Neurocrine Biosciences Presents One-Year Data Showing Sustained Efficacy of CRENESSITY (crinecerfont) in Adult Patients, at ENDO 2025. PR Newswire. July 14, 2025. Accessed July 21, 2025. https://www.prnewswire.com/news-releases/neurocrine-biosciences-presents-one-year-data-showing-sustained-efficacy-of-crenessity-crinecerfont-in-adult-patients-at-endo-2025-302503650.html

3. Auchus RJ, Hamidi O, Pivonello R, et al. Phase 3 trial of Crinecerfont in adult congenital adrenal hyperplasia. New England Journal of Medicine. 2024;391(6):504-514. doi:10.1056/nejmoa2404656