Patricia Fechner, MD, talks latest crinecerfont data for pediatric CAH

New 2-year findings from the phase 3 CAHtalyst Pediatric Study suggest that treatment with crinecerfont may provide sustained hormonal control while reducing glucocorticoid exposure in children and adolescents with classic congenital adrenal hyperplasia (CAH), according to data presented at the Pediatric Endocrine Society 2026 Annual Meeting in San Francisco, California.^1,2

The analysis included 86 participants aged 4 to 17 years who completed up to 2 years of treatment with crinecerfont in the open-label extension phase of the trial. Investigators reported durable reductions in adrenocorticotropic hormone (ACTH) and 17-hydroxyprogesterone (17-OHP), alongside reductions in daily glucocorticoid dosing.

At baseline, mean ACTH was 329 pg/mL. Investigators observed a reduction of 118 pg/mL at month 12 and 157 pg/mL at month 24. Mean 17-OHP levels decreased from 8682 ng/dL at baseline by 1698 ng/dL at month 12 and by 1924 ng/dL at month 24. Mean daily glucocorticoid dose also decreased from 16.4 mg/m²/day hydrocortisone equivalents at baseline by 2.9 mg/m²/day at month 12 and 3.2 mg/m²/day at month 24.

Growth and puberty implications in pediatric CAH

Patricia Fechner, MD, pediatric endocrinologist at Seattle Children’s Hospital, said the combination of androgen control and glucocorticoid reduction is particularly important in pediatric patients because of the effects excess androgens can have on growth and pubertal development.

“I think that pediatric patients are unique because they are growing excess androgen production, which can advance bone age, which then limits the amount of time they have to grow,” Fechner said. “It also causes them to go through puberty earlier.”

Fechner added that lower glucocorticoid exposure may help preserve growth potential while reducing complications associated with chronic steroid exposure.

“By giving them lower doses of glucocorticoid, we can then also maximize their growth, as excessive amounts of glucocorticoid suppress growth, but we also can decrease then the long-term complications of decreased bone mineral density and cardio metabolic problems,” she said.

Investigators also reported findings tied to androgen-related outcomes. Among participants with acne at baseline, mean acne severity scores decreased by 6.5 mm at month 12 and 11.0 mm at month 24. In female participants with baseline hirsutism, scores remained largely stable over 2 years despite lower glucocorticoid doses and pubertal progression.

According to Fechner, sustained androgen control could have long-term implications for growth and pubertal timing.

“I think that improved adrenal androgen control can have a significant impact on growth, allowing the child then to meet their full genetic potential for height,” she said. “It can also allow them to go through puberty at a more normal age, so that they go through it with their peers.”

Cardiometabolic outcomes improve over 2 years

The study also demonstrated improvements in measures associated with long-term glucocorticoid exposure. Among participants with overweight or obesity at baseline, 60% achieved at least a 0.2 reduction in body mass index (BMI) standard deviation score by month 24, and 23% achieved a BMI below the 85th percentile.

Among participants with baseline insulin resistance, 61% no longer met criteria for insulin resistance after 2 years of treatment.

Fechner said these findings may have implications for pediatric patients as they transition into adulthood.

“I think these findings are very significant: elevated BMI as a child goes through adolescence, then tends to continue into adulthood,” she said. “If we're able to decrease their BMI, I think that long term, they will also hopefully have decreased BMI.”

She also noted that improvements in acne may affect quality of life in pediatric patients.

“I think it suggests an improved quality of life. Acne can be very distressing for individuals, and so by having a decrease in acne, they have a better quality of life,” Fechner said.

Potential shift in the CAH treatment paradigm

Crinecerfont is an oral corticotropin-releasing factor type 1 receptor antagonist designed to reduce excess ACTH and adrenal androgens through a nonglucocorticoid mechanism. Patients receiving treatment continue glucocorticoid therapy for cortisol replacement.

Fechner said the therapy may help clinicians distinguish physiologic cortisol replacement from adrenal-suppression strategies that traditionally require supraphysiologic glucocorticoid doses.

“I think crinecerfont can separate the need for cortisol replacement to prevent adrenal insufficiency vs cortisol dosing to suppress the adrenal gland,” she said. “This then allows for more physiologic hydrocortisone replacement without the complications of excess hydrocortisone.”

References

1. Neurocrine Biosciences presents new two-year Crenessity (crinecerfont) data demonstrating durable hormone control, reduced glucocorticoid exposure and meaningful clinical improvements in pediatric patients with classic congenital adrenal hyperplasia. Press release. Neurocrine Biosciences. May 1, 2026. Accessed May 11, 2026.  https://www.prnewswire.com/news-releases/neurocrine-biosciences-presents-new-two-year-crenessity-crinecerfont-data-demonstrating-durable-hormone-control-reduced-glucocorticoid-exposure-and-meaningful-clinical-improvements-in-pediatric-patients-with-classic-congenital-302759774.html

2. Merke DP, Mallappa A, Engel ER, et al. Crinecerfont in pediatric congenital adrenal hyperplasia. N Engl J Med. 2024;391(6):493-503. doi:10.1056/NEJMoa2404655