Richard Auchus, MD: Crinecerfont's positive weight-related outcomes in children with CAH

Twelve-month findings from the Phase 3 CAHtalyst Pediatric trial presented at ENDO 2025 demonstrated that treatment with crinecerfont (Crenessity; Neurocrine Biosciences) led to improvements in weight-related outcomes for children with classic congenital adrenal hyperplasia (CAH) when combined with glucocorticoid therapy.¹

Richard Auchus, MD, PhD, professor of pharmacology and internal medicine at the University of Michigan, highlighted the metabolic risks these patients face. “Children with CAH have a high prevalence of obesity, as do adults with CAH, which places them at increased risk for cardiovascular disease,” he explained. "In adults, secondary to adrenal crisis, the second most common cause of death in CAH is cardiovascular disease. They have a significant metabolic risk, which begins developing in childhood due to prolonged exposure to the high doses of glucocorticoids traditionally necessary to manage the condition adequately."

The intention behind the trial was to determine whether adding crinecerfont—a CRF1 receptor antagonist—could lower adrenal androgens and allow for lower, more physiologic glucocorticoid doses. In the 28-week, double-blind period, androstenedione dropped by about 50% in the crinecerfont group, enabling an 18% glucocorticoid dose reduction, whereas dosing increased in the placebo group.

"In the crinecerfont group, BMI decreased following this period, whereas BMI slightly increased in the placebo group," said Auchus. "At the 28-week point, the placebo arm was crossed over into crinecerfont, and additional data presented showed that this transition resulted in reductions in androstenedione and 17-hydroxyprogesterone levels. This, in turn, allowed for glucocorticoid dose reduction and a subsequent decrease in BMI in the placebo group post-crossover."

According to a press release from Neurocrine Biosciences, pediatric patients on crinecerfont achieved reductions in BMI standard deviation scores (SDS) at Week 28, and these improvements were maintained through Week 52. For pediatric patients who were overweight or obese at baseline (~60%), a higher percentage on crinecerfont achieved at least a 0.2 reduction in BMI SDS compared to placebo.

Auchus noted that after the placebo group crossed over to crinecerfont, they too experienced reductions in BMI and hormone levels, though, “At 12 months, the improvement in BMI was greater in those who had received crinecerfont from the start," he said. “Even modest excesses in glucocorticoids appear harmful over the long term,” and underscored the value of early intervention.

Crinecerfont was approved by the FDA in December 2024 for use in adults and children aged 4 years and older with classic CAH, based on data showing meaningful reductions in glucocorticoid dosing and serum androgen levels. Its mechanism targets adrenal androgen overproduction directly, helping reduce reliance on high-dose steroids.²

READ MORE: Kyriakie Sarafoglou, MD, discusses crinecerfont FDA approval for congenital adrenal hyperplasia

“General pediatricians will encounter these patients… There is now an intervention that was not previously available,” Auchus added. “Evidence now shows that even small reductions in glucocorticoid dosing can significantly impact body weight and insulin sensitivity.”

References:

1. Neurocrine Biosciences presented one-year data from phase 3 CAHtalyst studies showing improvements in weight-related effects of glucocorticoid treatment at the 2025 Endocrine Society’s Annual Meeting. Neurocrine Biosciences. Press release. July 14, 2025. Accessed July 31, 2025.
2. Ebert M. FDA approves Crenessity for treatment of classic congenital adrenal hyperplasia. Contemporary Pediatrics. December 13, 2024. Accessed July 31, 2025. https://www.contemporarypediatrics.com/view/fda-approves-crenessity-for-treatment-of-classic-congenital-adrenal-hyperplasia