Erik Swain , 2025-05-15 18:52:00
Key takeaways:
- Crinecerfont enabled many children with congenital adrenal hyperplasia (CAH) to achieve reductions in glucocorticoid dose and androstenedione level.
- The drug improved hormone levels for adults with CAH.
ORLANDO — In patients with classic congenital adrenal hyperplasia, crinecerfont conferred meaningful reductions in glucocorticoid dose and androstenedione level in children and improved reproductive hormone levels in adults, new data show.
New findings from the CAHtalyst pediatric study and the CAHtalyst adult study of crinecerfont (Crenessity, Neurocrine Biosciences), which was approved by the FDA in December, were presented at the American Association of Clinical Endocrinology Annual Scientific and Clinical Conference.
New data from the CAHtalyst pediatric and adult studies revealed benefits of crinecerfont for people with classic congenital adrenal hyperplasia.
CAHtalyst pediatric study
As Healio previously reported, in the CAHtalyst pediatric study, children assigned crinecerfont were more likely to have reductions in glucocorticoid dose and androstenedione level than those assigned placebo at 28 weeks.
In the presentation at the AACE Annual Scientific and Clinical Conference, Patricia Y. Fechner, MD, medical director of Seattle Children’s Congenital Adrenal Hyperplasia Center and professor of pediatrics at the University of Washington School of Medicine, said by week 4, 74% of the crinecerfont group had androstenedione levels below the upper limit of normal compared with 12% of the placebo group.
Patricia Y. Fechner
The percentage of patients achieving at least a 30% reduction of androstenedione levels between baseline and week 4 was 85% in the crinecerfont group and 18% in the placebo group, whereas the percentage improving from at least 1.5 times the upper limit of normal to below the upper limit of normal was 61% in the crinecerfont group and 0% in the placebo group, she said.
Those who had a reduction in androstenedione levels by week 4 were more likely to have a reduction in glucocorticoid dose by week 28 (crinecerfont, –18%; placebo, +6%; least squares mean difference, –24 percentage points; 95% CI, –30 to –17; P < .0001), she said.
She also said 30% of the crinecerfont group reached a physiologic dose of glucocorticoids at week 28 while maintaining or improving androstenedione levels, but no child in the placebo group accomplished that.
A reduction in glucocorticoid dose of at least 2.5 mg/m2 per day by week 28 occurred in 51% of the crinecerfont group and 3% of the placebo group, whereas the percentage of patients who achieved that or a physiologic dose (defined as < 11 mg/m2 per day) was 57% in the crinecerfont group and 3% in the placebo group, Fechner said.
The percentage of patients who achieved at least one threshold related to glucocorticoid dose and/or androstenedione level was 90% in the crinecerfont group and 21% in the placebo group, she said.
“Crinecerfont was well tolerated, with few serious adverse events and no adrenal crisis,” Fechner said during the presentation. “[The study] demonstrates that clinicians can focus on reducing androgens, lowering glucocorticoid dose or both based on the individual patient’s treatment goals.”
CAHtalyst adult study
In new data from the CAHtalyst adult study, the crinecerfont group was more likely to have improved levels of reproductive hormones than the placebo group, Sonal Vaid, MD, physician scientist at the NIH Clinical Center, said during a presentation.
At week 24 in the randomized phase and 12 months in the open-label phase, male patients assigned crinecerfont were more likely to have normalization of luteinizing hormone than those assigned placebo (week 24, 47% vs. 22%; month 12, 65% vs. 44%), and at 12 months, male patients assigned crinecerfont were more likely to have normalization of follicle-stimulating hormone (36% vs. 14%), she said.
Among male patients with elevated androstenedione-to-testosterone ratio at baseline, the crinecerfont group was more likely than the placebo group to achieve normalization by week 24 (19% vs. 5%), whereas 24% in both groups achieved normalization at 12 months in the open-label study, she said.
At 24 weeks, female patients in the crinecerfont group were more likely to achieve normalization of testosterone levels (11% vs. 0%) and progesterone levels (14% vs. 6%), and some patients from both groups achieved normalization at 12 months despite substantially reduced glucocorticoid doses, Vaid said.
The most common adverse events associated with crinecerfont were headache and fatigue, she said.
“Crinecerfont, a novel therapeutic option for reducing excess androgens and enabling the lowering of glucocorticoids to more physiologic doses, may also represent a promising approach to improving reproductive hormones in adults with [congenital adrenal hyperplasia],” Vaid said during the presentation.
Reference:
- Vaid S, et al. Crinecerfont improves reproductive hormones in classic congenital adrenal hyperplasia: 1-year results from the CAHtalyst adult study. Presented at: American Association of Clinical Endocrinology Annual Scientific and Clinical Conference; May 15-17, 2025; Orlando.
Sources/Disclosures
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Fechner PY, et al. Crinecerfont allows for more physiologic glucocorticoid treatment with greater reductions of androstenedione in pediatric patients with classic congenital adrenal hyperplasia: Analyses of individual patient data from the CAHtalyst pediatric study. Presented at: American Association of Clinical Endocrinology Annual Scientific and Clinical Conference; May 15-17, 2025; Orlando.
Disclosures:
The studies were funded by Neurocrine Biosciences. Fechner reports receiving research grants from Diurnal Ltd. (now Neurocrine UK Ltd.), Neurocrine Biosciences and Spruce Biosciences; serving on an advisory board for Neurocrine Biosciences; and consulting for Eton Pharmaceuticals. Vaid reports no relevant financial disclosures.
