Core Insights - Neurocrine Biosciences presented new data from the Phase 3 CAHtalyst studies showing that CRENESSITY® (crinecerfont) leads to significant improvements in weight-related outcomes for patients with classic congenital adrenal hyperplasia (CAH) [1][2][5] Group 1: Study Overview - The Phase 3 CAHtalyst program is the largest interventional clinical trial for classic CAH, involving 285 patients (103 pediatric and 182 adult) [2][12] - The studies included a double-blind, placebo-controlled period followed by an open-label period where all patients received CRENESSITY [2][12] Group 2: Weight-Related Outcomes - Adult patients treated with CRENESSITY showed a mean BMI reduction of 0.8 kg/m² compared to a 0.4 kg/m² reduction in the placebo group at Month 12 [4][6] - 39% of adult patients on CRENESSITY achieved over a 5% weight reduction, compared to 14% in the placebo group [4][6] - Pediatric patients on CRENESSITY maintained reductions in BMI standard deviation scores (SDS) through Week 52, while those on placebo saw an increase [6][4] Group 3: Insulin Resistance Improvements - Significant reductions in insulin resistance were observed in both adult and pediatric patients treated with CRENESSITY compared to placebo [5][6] - The mean HOMA-IR score decreased more significantly in the CRENESSITY group than in the placebo group [6][7] Group 4: Safety Profile - CRENESSITY demonstrated a favorable safety profile, with common side effects being mild to moderate and not leading to discontinuation of the drug [8][20] - Common side effects in children included headache and stomach pain, while adults reported fatigue and headache [8][22] Group 5: Regulatory and Market Context - Data from the CAHtalyst studies supported the FDA approval of CRENESSITY in December 2024 [15] - CRENESSITY is positioned to evolve the standard of care for classic CAH by allowing for reduced glucocorticoid doses while maintaining or improving androgen control [2][16]

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]