ENDO 2026 data highlight CRENESSITY’s long-term benefits in classic CAH, including reduced glucocorticoid exposure, improved growth outcomes, cardiometabolic and bone health gains, and first evidence in 11β-hydroxylase deficiency
Written By: Dr. Preethi Putti, PharmD
Reviewed By: Pharmacally Editorial Team
Neurocrine Biosciences reported a broad set of new findings for CRENESSITY® (crinecerfont) at ENDO 2026, highlighting long-term benefits across pediatric and adult patients with classic congenital adrenal hyperplasia (CAH), as well as the first clinical evidence in patients with the rare 11β-hydroxylase deficiency subtype. The data showed sustained reductions in glucocorticoid exposure, improvements in growth outcomes among children, favorable cardiometabolic and bone health trends in adults, and meaningful hormonal control in a previously unstudied CAH population.
Scientific and Clinical Basis
Classic CAH is a rare inherited endocrine disorder characterized by impaired cortisol production and excess adrenal androgen secretion. Standard treatment relies on glucocorticoids to replace missing cortisol and suppress excess hormone production. However, prolonged use of supraphysiologic glucocorticoid doses can contribute to obesity, insulin resistance, cardiovascular complications, osteoporosis, and impaired growth in children.
CRENESSITY is an oral corticotropin-releasing factor type 1 (CRF1) receptor antagonist that lowers adrenocorticotropic hormone (ACTH) and adrenal androgen production through a non-glucocorticoid mechanism. By improving hormonal control, the therapy allows patients to reduce glucocorticoid exposure while maintaining disease management.
Trial and Development Details
Pediatric CAH: Improved Growth Outcomes After Two Years
New analyses from the Phase 3 CAHtalyst Pediatric study (NCT04806451) focused on growth outcomes in children and adolescents receiving CRENESSITY for up to two years. Among patients with advanced bone age at baseline, treatment slowed skeletal maturation and improved projected adult height.
In a subset of 24 patients with accelerated bone age, mean bone age standard deviation score decreased by 1.12, while predicted adult height increased by an average of 4.7 cm. Investigators reported that most patients experienced stabilization or improvement in bone age progression, suggesting that long-term hormonal control combined with reduced glucocorticoid exposure may positively influence growth during critical developmental years. CRENESSITY remained generally well tolerated, with no new safety signals identified.
Adult CAH: Cardiometabolic and Bone Health Benefits
Two-year findings from the Phase 3 CAHtalyst Adult study (NCT04490915) demonstrated sustained reductions in glucocorticoid use alongside improvements in weight-related and metabolic measures.
Among adults who were overweight or obese at baseline, 37% achieved clinically meaningful weight loss exceeding 5% of body weight after two years. In patients with insulin resistance at baseline, 43% no longer met criteria for insulin resistance at the two-year assessment. Mean daily glucocorticoid dose declined by approximately 38% from baseline.
Investigators also reported favorable trends in bone mineral density and bone turnover markers, suggesting potential recovery from long-term glucocorticoid-associated skeletal effects. No new safety concerns emerged during extended treatment.
First Evidence in 11β-Hydroxylase Deficiency CAH
Neurocrine also presented the first retrospective case series evaluating CRENESSITY in patients with classic CAH caused by 11β-hydroxylase deficiency, a rare subtype representing roughly 5% of CAH cases.
The analysis included 15 pediatric and adult patients. Following CRENESSITY initiation, investigators observed substantial reductions in disease-related hormones and steroid precursors. Median reductions reached 95% for 11-deoxycortisol, 92% for 11-deoxycorticosterone, and 65% for androstenedione among patients with elevated baseline levels.
Fourteen of 15 patients reduced their glucocorticoid dose, while two of five patients receiving antihypertensive therapy reduced or discontinued those medications. Hormone normalization occurred as early as one month after treatment initiation in several cases.
Clinical Implications
Collectively, the findings extend the clinical profile of CRENESSITY beyond androgen control alone. Neurocrine executives and investigators emphasized that reducing chronic glucocorticoid exposure may translate into meaningful long-term benefits affecting growth, metabolic health, bone integrity, and overall disease burden.
The pediatric data address one of the most challenging aspects of CAH management, preserving adult height potential, while the adult results provide evidence that sustained hormonal control may improve key markers associated with long-term cardiometabolic risk. The 11β-hydroxylase deficiency findings further broaden understanding of the therapy’s potential across the CAH spectrum.
Implications for Clinical Practice
CRENESSITY received FDA approval in December 2024 as an adjunctive treatment for adults and children aged four years and older with classic CAH. The ongoing CAHtalyst open-label extension studies continue to evaluate long-term safety and clinical outcomes.
The new ENDO 2026 data strengthen evidence supporting sustained glucocorticoid reduction while maintaining disease control and may define future treatment strategies focused on reducing the long-term complications associated with conventional steroid-based management. Additional analyses from ongoing extension studies and real-world experience are expected to further clarify the therapy’s long-term impact across diverse CAH populations.
References
About the Writer
Dr.Preethi Putti, PharmD (LinkedIn) is a pharmaceutical researcher with experience in healthcare and pharmaceutical market research and competitive intelligence. She specializes in analyzing drug pipelines, clinical data, and industry trends and translating complex scientific data into clear and structured medical content. Strong foundation in clinical research, data interpretation, and evidence-based healthcare analysis. Committed to advancing a global career in clinical research and healthcare innovation.