Core Insights - Neurocrine Biosciences announced significant findings from the Phase 3 CAHtalyst Pediatric study, demonstrating lasting reductions in glucocorticoid doses and improvements in clinical outcomes for pediatric patients with classic congenital adrenal hyperplasia (CAH) treated with CRENESSITY (crinecerfont) for up to one year [1][2][12] Group 1: Clinical Study Findings - The Phase 3 CAHtalyst Pediatric study included 103 pediatric patients aged 4 to 17 years, making it the largest interventional clinical trial program for classic CAH [2][10] - Patients receiving CRENESSITY showed a mean glucocorticoid dose reduction from 16.4 mg/m²/d at baseline to 13.5 mg/m²/d at Week 52, a decrease of 2.9 mg/m²/d [3] - Improvements in clinical outcomes included a reduction in mean body mass index (BMI) standard deviation scores by -0.09 in the CRENESSITY group compared to -0.02 in the placebo group [3] Group 2: Hormonal and Clinical Outcomes - Adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), and androstenedione (A4) levels remained below baseline levels in patients treated with CRENESSITY, despite reduced glucocorticoid doses [1][4] - The proportion of patients achieving glucocorticoid doses within the physiologic range (≤11 mg/m²/d hydrocortisone equivalents) remained stable from Week 28 (30%) to Week 52 (32%) [4] Group 3: Safety and Tolerability - CRENESSITY was generally well tolerated, with no adrenal crises reported during the double-blind placebo-controlled (DBPC) period [5] - The most common adverse reactions included headache (25% vs. 6% for placebo), abdominal pain (13% vs. 0%), and fatigue (7% vs. 0%) [5] Group 4: Treatment Implications - CRENESSITY allows for a reduction in glucocorticoid doses while maintaining or improving hormonal levels, potentially transforming the treatment landscape for children and adolescents with classic CAH [2][14] - The study supports the ongoing use of CRENESSITY in conjunction with glucocorticoids for effective management of CAH [16]

Core Insights - Neurocrine Biosciences announced positive Phase 3 data for CRENESSITY (crinecerfont) in treating congenital adrenal hyperplasia (CAH), showing significant improvements in hormone levels and glucocorticoid dose reductions in both pediatric and adult patients [1][3][16] Group 1: Study Results - In the pediatric study, 90% of participants on CRENESSITY achieved at least one threshold for androstenedione reduction or glucocorticoid reduction, compared to 21% on placebo [7][8] - At Week 28, 30% of pediatric participants on CRENESSITY reached a physiologic glucocorticoid dose while maintaining or improving androstenedione levels, whereas no placebo participants achieved this [8] - In the adult study, at Week 24, 47% of male patients on CRENESSITY normalized luteinizing hormone (LH) levels compared to 22% on placebo [10] Group 2: Treatment Mechanism - CRENESSITY is a novel oral corticotropin-releasing factor type 1 receptor antagonist that aims to reduce excess adrenal androgens and allow for lower glucocorticoid doses, addressing complications from high-dose steroid use [3][17] - The drug works by decreasing adrenocorticotropic hormone (ACTH) levels, which in turn reduces the production of adrenal androgens, potentially alleviating symptoms associated with CAH [17] Group 3: Safety and Tolerability - CRENESSITY was generally well tolerated in pediatric patients, with no adrenal crises reported during the double-blind treatment period [5] - The most common adverse reactions in pediatric patients included headache (25% vs. 6% for placebo) and abdominal pain (13% vs. 0%) [5] - In adult patients, 1.6% experienced adrenal crisis while on CRENESSITY, with common side effects including fatigue (25% vs. 15% for placebo) and headache (16% vs. 15%) [10]