Neurocrine Biosciences Presented CAHtalyst™ Phase 3 Pediatric and Adult Studies, CAHtalog™ Registry and Disease- and Glucocorticoid-Related Comorbidities Data in CAH at ENDO 2024

Core Insights - Neurocrine Biosciences and Diurnal Ltd. presented data from their neuroendocrinology pipeline at the Endocrine Society Annual Meeting, focusing on the CAHtalyst Phase 3 studies of crinecerfont for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency [1][2][15] - The CAHtalyst Phase 3 studies demonstrated significant efficacy in reducing glucocorticoid (GC) dosing while maintaining androgen control in both pediatric and adult patients [3][4][15] CAHtalyst Phase 3 Data - In adult patients, 63% of those treated with crinecerfont achieved a reduction in GC dosing to physiologic range (≤ 11 mg/m²/day) at Week 24, compared to 18% in the placebo group [3] - In pediatric patients, 29.9% of crinecerfont participants achieved a similar reduction in GC dosing at Week 28, while 0% of placebo participants did [4] CAHtalog Registry Findings - A real-world study from the CAHtalog registry highlighted the negative impacts of high GC doses, including premature adiposity rebound and early growth acceleration in pediatric patients [5][6] - The study found that 27.3% of pediatric patients received high GC doses (>15 mg/m²/day), which were associated with significant comorbidities such as hypertension and metabolic complications [5][6] Natural History of CAH - Longitudinal data from the CAHtalog registry indicated abnormal growth patterns in pediatric patients, with early growth acceleration followed by blunted pubertal growth, particularly in females [7] - The study also reported high rates of obesity and comorbidities among adult patients, with 83% of females and 100% of males having a BMI ≥ 25 kg/m² [7] Comorbidity Analysis - A claims-based cohort analysis revealed that CAH patients had significantly higher rates of comorbidities compared to the general population, including anxiety disorders (34% vs. 26%) and obesity (23% vs. 13%) [10][11] - The data underscored the chronic clinical burden of CAH, emphasizing the need for optimized disease management strategies [11] Crinecerfont Overview - Crinecerfont is an investigational oral CRF1 antagonist aimed at reducing ACTH and adrenal androgens through a glucocorticoid-independent mechanism [14][15] - The ongoing CAHtalyst studies are designed to evaluate the safety, efficacy, and tolerability of crinecerfont in patients with CAH due to 21-hydroxylase deficiency [15]