Two-Year CRENESSITY Data Shows Sustained Benefits in Pediatric and Adult CAH Patients
核心洞察
New two-year data from the CAHtalyst trials demonstrate that CRENESSITY (搜索) (crinecerfont) provides sustained reductions in glucocorticoid doses and durable androgen control in both pediatric and adult patients with classic congenital adrenal hyperplasia (搜索).
In pediatric patients, 60% of those who were overweight or obese at baseline experienced clinically meaningful improvements in body mass index, while 61% of those with insulin resistance (搜索) at baseline were no longer insulin resistant after two years of treatment.
Adult patients maintained substantial glucocorticoid dose reductions with 69% reaching physiologic-range dosing at two years, and 75% of participants originally taking dexamethasone successfully transitioned to dexamethasone-free regimens.
Adults and children with classic congenital adrenal hyperplasia (搜索) (CAH (搜索)) experienced sustained clinical benefits with CRENESSITY (搜索) (crinecerfont) treatment over two years, according to new data from the CAHtalyst trials presented at recent medical conferences. The findings demonstrate durable hormone control, reduced glucocorticoid exposure, and meaningful improvements in clinical outcomes associated with excess androgens and long-term glucocorticoid treatment.
Adult Population Maintains Glucocorticoid Reductions
Two-year open-label extension data from the CAHtalyst adult trial, presented at the American Association of Clinical Endocrinology Annual Scientific and Clinical Conference, showed that substantial reductions in glucocorticoid doses were maintained in 182 adults with classic CAH (搜索). By 24 months, mean glucocorticoid doses fell to a physiological range of less than 11 mg/m² per day, with 69% of participants reaching that dose or lower.
"Crinecerfont is a novel therapeutic option for reducing excess androgens and enabling the lowering of glucocorticoids (搜索) to more physiologic doses, which we hope will improve long-term outcomes for these patients well into adulthood," said Richard J. Auchus, MD, PhD, the trial's principal investigator and professor of pharmacology and internal medicine in the division of metabolism, endocrinology and diabetes at the University of Michigan.
The study demonstrated impressive treatment transitions among participants. At two years, 62% of participants taking two or more doses of hydrocortisone reduced their dose frequency by at least one dose per day. Additionally, 33% of those taking prednisone or an equivalent with or without hydrocortisone were taking hydrocortisone only, and 75% of participants originally taking dexamethasone were changed to dexamethasone-free regimens.
Pediatric Patients Show Metabolic Improvements
The pediatric data, presented at the Pediatric Endocrine Society 2026 Annual Meeting, included 86 participants aged four to 17 years who completed up to two years of CRENESSITY (搜索) treatment. The results showed particularly notable improvements in metabolic outcomes that are critical during growth and development.
Among participants with obesity (搜索) at baseline (BMI ≥85th percentile), 60% achieved clinically meaningful improvements (≥0.2 reduction) in BMI standard deviation score at month 24, including 23% who achieved a BMI <85th percentile. Perhaps more significantly, among participants with insulin resistance (搜索) at baseline, 61% had a homeostatic model assessment of insulin resistance (HOMA-IR) value that no longer met the criteria for insulin resistance after two years of treatment.
"In pediatric patients with classic congenital adrenal hyperplasia (搜索), excess androgens can accelerate bone age and drive early puberty, which can result in reduced final adult height. This, along with chronic supraphysiologic glucocorticoid exposure, can impact cardiometabolic health and quality of life in patients with CAH (搜索)," said Mimi Kim, MD, MSc, Associate Professor of Clinical Pediatrics, Keck School of Medicine, University of Southern California, and Principal Investigator for CAHtalyst Pediatric.
Sustained Hormone Control Across Populations
Both studies demonstrated meaningful and durable reductions in key hormonal markers. In pediatric patients, substantial reductions in mean adrenocorticotropic hormone (ACTH) and 17-hydroxyprogesterone (17-OHP) were observed at 12 months, with further reductions at 24 months, despite sustained decreases in glucocorticoid doses during the same period.
The pediatric data also showed improvements in outcomes related to excess androgens. Among patients with acne (搜索) at baseline (visual analog scale score >0; mean baseline score: 25.4 mm; n=58), mean acne severity decreased by 6.5 mm at month 12 and by 11.0 mm at month 24, indicating progressive improvement over time. Among male participants Tanner stage 2 or above with an androstenedione-to-testosterone ratio ≥0.5 at baseline, 31% and 36% achieved a ratio <0.5 at months 12 and 24, respectively.
Safety Profile Remains Favorable
Long-term safety data continued to support CRENESSITY (搜索)'s tolerability profile. In adults, most adverse events were assessed as mild or moderate, with the main adverse events during the double-blind, placebo-controlled portion being headache and fatigue. Importantly, the 1- and 2-year data suggest these symptoms were due to glucocorticoid withdrawal rather than the drug itself.
"When the patients who were taking placebo crossed over to crinecerfont during the second 6 months, their glucocorticoid dose reduction schedule was once a month, not once every 2 weeks like the protocol of the first 6 months," Auchus explained. "The incidence of headache and fatigue, adverse effects that were higher in the crinecerfont group, were much lower during that second phase. That result tells us that we need to take our time reducing the glucocorticoid dose."
The pediatric population showed similar tolerability, with more than 80% study retention at two years and no new safety signals observed. The high retention rates across both studies—91% at one year in adults—underscore patient and physician confidence in the treatment.
Clinical Impact and Future Directions
The sustained benefits observed across both populations represent a significant advancement in CAH (搜索) management. As Auchus noted, "We had women [with CAH] that were taking one dose of hydrocortisone a day and had perfectly normal labs and regular menses. That is unheard of."
"These findings underscore the potential for CRENESSITY (搜索) to redefine the treatment paradigm for patients with CAH (搜索) by providing sustained control of androgens and allowing for significant reductions in glucocorticoid dosing – this could ultimately lead to important improvements in key long-term patient outcomes," Kim added.
CRENESSITY (搜索), approved by the FDA in December 2024, works as a potent and selective oral corticotropin-releasing factor type 1 receptor (搜索) (CRF1 (搜索)) antagonist that reduces excess ACTH and adrenal androgens through a non-glucocorticoid mechanism. Neurocrine Biosciences plans to share additional two-year data on clinical endpoints and outcomes at upcoming medical meetings.