Crenessity (crinecerfont) / Neurocrine, Sanofi - LARVOL DELTA

Game Changers: Blockbuster Small-Molecule Drugs Approved by the FDA in 2024. (PubMed, Pharmaceuticals (Basel)) - "Notably, eight of these drugs (including Rezdiffra®, Voydeya®, Iqirvo®, Voranigo®, Livdelzi®, Miplyffa®, Revuforj®, and Crenessity®) are classified as "first-in-class" and have received breakthrough therapy designation. These agents not only exhibit distinct mechanisms of action but also offer substantial improvements in efficacy for patients compared to prior therapeutic options. This article offers a comprehensive analysis of the mechanisms of action, clinical trials, drug design, and synthetic methodologies related to representative drugs, aiming to provide crucial insights for future pharmaceutical development."

FDA event • Journal • Review • Alopecia • Brain Cancer • Breast Cancer • Cardiovascular • Chronic Kidney Disease • Chronic Obstructive Pulmonary Disease • CNS Disorders • Congenital Adrenal Hyperplasia • Cystic Fibrosis • Dermatology • Duchenne Muscular Dystrophy • Endocrine Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Glioma • Hematological Disorders • Hematological Malignancies • Hepatology • Hypertension • Immunology • Infectious Disease • Leukemia • Lung Cancer • Lysosomal Storage Diseases • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Muscular Dystrophy • Nephrology • Non Small Cell Lung Cancer • Oncology • Primary Biliary Cholangitis • Psychiatry • Pulmonary Disease • Renal Disease • Respiratory Diseases • Schizophrenia • Solid Tumor • Ventricular Tachycardia

Crinecerfont Improves Reproductive Hormones in Classic Congenital Adrenal Hyperplasia: 1-Year Results from the CAHtalyst™ Adult Study (AACE 2025) - P3 | "Gonadal dysfunction with classic congenital adrenal hyperplasia (CAH) is due to testicular adrenal rest tumors and/or poor hormonal control in males and to high adrenal androgens and progesterone in females. Reproductive hormones were measured in the CAHtalystTM Adult (NCT04490915) study."

Clinical • Congenital Adrenal Hyperplasia • Endocrine Disorders • Oncology

Crinecerfont Allows for More Physiologic Glucocorticoid Treatment With Greater Reductions of Androstenedione in Pediatric Patients With Classic Congenital Adrenal Hyperplasia: Analyses of Individual Patient Data From the CAHtalyst™ Pediatric Study (AACE 2025) - P3 | "In the CAHtalystTM Pediatric (NCT04806451) study, children and adolescents with classic congenital adrenal hyperplasia (CAH) (2-17 years) were randomized to 28 weeks of double-blind treatment with placebo or crinecerfont, a novel corticotropin releasing factor type 1 receptor antagonist."

Clinical • Congenital Adrenal Hyperplasia • Endocrine Disorders • Pediatrics

Lunch Product Theater: Advancing Adult Patient Care in Classic Congenital Adrenal Hyperplasia: A Spotlight on CRENESSITY™ (crinecerfont) sponsored by Neurocrine Biosciences, Inc. (AACE 2025) - "Explore findings from the CAHtalyst™ study, which evaluated outcomes in patients undergoing protocolized GC dose reductions while taking CRENESSITY™ (crinecerfont), a selective CRF1 antagonist indicated for the treatment of classic congenital adrenal hyperplasia. To get to this product theater, enter through the Learning Zone."

Clinical • Congenital Adrenal Hyperplasia • Endocrine Disorders

New therapeutic steroid sparing options for Congenital Adrenal Hyperplasia (ESPE-ESE 2025) - "Crinecerfont, a corticotropin- releasing factor type 1 receptor (CRF1) antagonist was trialed in placebo-controlled studies for children and adults with 21OHD. Additional therapeutics targeting the HPA axis are in trials, particularly atumelnant, an orally administered MC2R (ACTH receptor) antagonist, and Lu AG13909, an antibody to ACTH. These treatments might allow simplified and less toxic glucocorticoid regimens for children and adults with 21OHD, to improve short- and long-term outcomes."

CNS Disorders • Congenital Adrenal Hyperplasia • Endocrine Disorders • Metabolic Disorders • Mood Disorders • Obesity • Osteoporosis • Pediatrics • Psychiatry

Crinecerfont Enables Glucocorticoid Dose Reductions While Maintaining/Improving Androstenedione in Paediatric Patients with Congenital Adrenal Hyperplasia: Subgroup Analyses From CAHtalyst™ Paediatric (ESPE-ESE 2025) - No abstract available

Clinical • Congenital Adrenal Hyperplasia • Endocrine Disorders • Pediatrics

Symposium 27: Novel treatment options for adrenal insuffiency/CAH (ESPE-ESE 2025) - "Your key learning points for this session will be:Long-term health outcomes in adults with classic 21OHD are poor and mostly reflect high glucocorticoid exposure.Crinecerfont, a corticotropin-releasing factor type 1 receptor (CRF1) antagonist lowered androstenedione and allowed glucocorticoid dose reduction in children and adults with classic 21OHD.Atumelnant is an MC2R (ACTH receptor) antagonist in clinical trials for classic 21OHD.Lu AG13909 is an anti-ACTH antibody in clinical trials for classic 21OHD.• The discovery of 11-oxygenated androgens, particularly 11-ketotestosterone (11KT), challenges the long-standing view that only testosterone and DHT are potent androgens in human physiology. Patients with adrenal insufficiency require individualised replacement with corticosteroidsMany patients have normal quality of lifeConventional twic or trice daily hydrocortisone or cortisone acetate is adequate for the majorityExtended-release formulations may be..."

Castration-Resistant Prostate Cancer • Congenital Adrenal Hyperplasia • Endocrine Disorders • Genito-urinary Cancer • Nephrology • Oncology • Polycystic Ovary Syndrome • Prostate Cancer • Renal Disease • Solid Tumor

Crinecerfont Enables Glucocorticoid Dose Reductions While Maintaining/Improving Androstenedione in Paediatric Patients with Congenital Adrenal Hyperplasia: Subgroup Analyses From CAHtalyst™ Paediatric (ESPE-ESE 2025) - P3 | "GC doses were kept stable for 4 weeks to evaluate the impact on androgens and then reduced to a target of 8-10 mg/m2/d in hydrocortisone equivalents (HCe) by Week 28 while maintaining/improving A4 relative to baseline (BL). Crinecerfont enabled GC dose reductions while maintaining/improving A4 in paediatric patients with CAH across multiple subgroups. These results demonstrate that paediatric patients with CAH can derive the androgen-lowering and GC-lowering benefits of crinecerfont regardless of region, sex, race, age, weight/BMI, pubertal stage, or pretreatment A4 level or GC dose."

Clinical • Congenital Adrenal Hyperplasia • Endocrine Disorders • Pediatrics

Neurocrine Biosciences Announces New Results from Exploratory Analyses of the Phase 3 CAHtalyst Pediatric Study Demonstrating CRENESSITY Reduces Glucocorticoid Dosing While Maintaining or Improving Androstenedione Across Patient Subgroups (PRNewswire) - P3 | N=104 | CAHtalyst Pediatric Study (NCT04806451) | Sponsor: Neurocrine Biosciences | "These data will be presented at the 2025 Joint Congress of European Society for Paediatric Endocrinology and the European Society of Endocrinology in Copenhagen, Denmark...Across all subgroups, CRENESSITY enabled reduction of GC doses while maintaining or improving A4 levels: Substantial Reduction in Adrenal Androgens at Week 4: CRENESSITY significantly reduced A4 levels from baseline compared with placebo (overall, -6.9 versus +2.5 nmol/L; LS mean difference [LSMD]: -9.3 nmol/L; p=0.0002); subgroup analyses of A4 reduction at Week 4 were consistent with the results in the overall population; Substantial Reduction in GC Doses at Week 28: GC doses were significantly reduced from baseline with CRENESSITY (while maintaining or improving A4 levels) compared with placebo (overall, -18.0% versus +5.6%; LSMD: -23.5%; p<0.0001); subgroup analyses of GC reduction at Week 28 were consistent..."

P3 data • Congenital Adrenal Hyperplasia

Crinecerfont Improves Reproductive Hormones in Classic Congenital Adrenal Hyperplasia: 1-Year Results from the Phase 3 CAHtalyst™ Adult Study (ESPE-ESE 2025) - No abstract available

Clinical • P3 data • Congenital Adrenal Hyperplasia • Endocrine Disorders

Crinecerfont Improves Reproductive Hormones in Classic Congenital Adrenal Hyperplasia: 1-Year Results from the Phase 3 CAHtalyst™ Adult Study (ESPE-ESE 2025) - P3 | "Background : Gonadal dysfunction with classic congenital adrenal hyperplasia (CAH) is due to testicular adrenal rest tumors and/or poor hormonal control (males) and to high adrenal androgens and progesterone (P4) (females). Crinecerfont has been shown to reduce ACTH, androgens, and androgen precursors in paediatric and adult patients with CAH. These analyses from CAHtalyst Adult indicate potential normalisation of reproductive hormones with crinecerfont, even with substantial GC dose reductions. CRF1 antagonism may be a promising therapeutic approach for improving reproductive hormones in adults with CAH."

Clinical • P3 data • Congenital Adrenal Hyperplasia • Endocrine Disorders • Oncology • Pediatrics

Crinecerfont Enables Reduction of Glucocorticoid Doses While Maintaining or Improving Androstenedione in Adults with Classic Congenital Adrenal Hyperplasia: Subgroup Analyses From the Phase 3 CAHtalyst™ Adult Study (ENDO 2025) - P3 | "GC doses were kept stable for 4 weeks to evaluate the impact on androgens, followed by a planned GC down-titration over 8 weeks to a target of 8-10 mg/m2/d in hydrocortisone (HC) equivalents...Changes from BL in A4 at Week 4 and in GC dose at Week 24 were analyzed in the overall population and in subgroups categorized by: region (US, outside US), sex (male, female), body mass index (ULN; evaluated for A4 change only). In 182 randomized participants (crinecerfont, n=122; placebo, n=60), mean A4 at BL was 620±729 ng/dL; mean GC dose was 17.6±4.9 mg/m2/d (32.3±9.3 mg/d)... Crinecerfont was effective in enabling GC dose reductions while maintaining or improving A4 in adults with CAH across all subgroups analyzed. These results demonstrate that adults with CAH can derive the androgen-lowering and GC-lowering benefits of crinecerfont treatment regardless of sex, race, BMI, or pre-treatment A4 levels, GC dose, or GC regimen.*. .*"

Clinical • P3 data • Congenital Adrenal Hyperplasia • Endocrine Disorders • Pediatrics

Crinecerfont Shows Favorable Trends in Improving Weight-Related Outcomes in Pediatric Patients With Classic Congenital Adrenal Hyperplasia: 1-Year Results from the CAHtalyst™ Pediatric Study (ENDO 2025) - P3 | "Children and adolescents with CAH who received up to 1 year of crinecerfont showed reductions in BMI SDS. Moreover, one-third of participants who were overweight or obese at baseline achieved a ≥0.15 reduction in BMI SDS with crinecerfont, and 13% achieved normal BMI. These analyses indicate that the GC dose reductions enabled by crinecerfont can allow for improvements in the weight-related effects associated with chronic supraphysiologic GC exposure.*."

Clinical • Congenital Adrenal Hyperplasia • Endocrine Disorders • Genetic Disorders • Obesity • Pediatrics

Crinecerfont Allows for More Physiologic Glucocorticoid Dosing Regimens in Patients With Classic Congenital Adrenal Hyperplasia: Results from the Phase 3 CAHtalyst™ Adult and CAHtalystTM Pediatric Studies (ENDO 2025) - P3 | "In both studies, GC was kept stable for the first 4 weeks to measure the impact on androgens and then reduced to a target of 8-10 mg/m2/d in hydrocortisone (HC) equivalents at the end of double-blind treatment (Week 28 [pediatric]; Week 24 [adult]) while maintaining or improving androstenedione (A4) relative to baseline (BL). Long-acting, synthetic GCs (dexamethasone [DEX], (methyl)prednis(ol)one [PRED]) and timing (bedtime dose) were to be decreased first...Fludrocortisone was continued as needed. In CAHtalyst Pediatric (N=103), mean GC dose at BL was 16.4 mg/m2/d; 92.2% were taking only HC (no DEX or PRED)... Patients with CAH who received crinecerfont for ~6 months had greater mean decreases in GC doses while maintaining or improving A4 compared to placebo. HC dosing frequency was more likely to decrease with crinecerfont, as was switching to DEX- and PRED-free regimens. These changes reduce the CAH treatment burden and may decrease the risk of adverse effects of..."

Clinical • P3 data • Congenital Adrenal Hyperplasia • Endocrine Disorders • Pediatrics

Crinecerfont Shows Favorable Trends in Improving Clinical Outcomes in Children and Adolescents With Classic Congenital Adrenal Hyperplasia: 1-Year Results From the CAHtalyst™ Pediatric Study (ENDO 2025) - P3 | "Children and adolescents with CAH who received up to 1 year of crinecerfont showed improvements in BMI and insulin resistance. Hirsutism in female participants improved with crinecerfont, despite substantial reductions in GC dose. Given the known adverse effects of androgen excess and GC exposure, these results represent a promising therapeutic advancement in CAH.*."

Clinical • Clinical data • Congenital Adrenal Hyperplasia • Dyslipidemia • Endocrine Disorders • Pediatrics

Crinecerfont Improves Reproductive Hormones in Classic Congenital Adrenal Hyperplasia: 1-Year Results from the Phase 3 CAHtalyst™ Adult Study (ENDO 2025) - P3 | "Background: Gonadal dysfunction with classic congenital adrenal hyperplasia (CAH) is due to testicular adrenal rest tumors and/or poor hormonal control (males) and to high adrenal androgens and progesterone (P4) (females). Crinecerfont has previously been shown to substantially reduce ACTH, adrenal androgens, and androgen precursors in phase 2 and/or phase 3 studies with pediatric and adult patients with CAH. These analyses from the CAHtalyst Adult study indicate that normalization of reproductive hormones could also be achieved with crinecerfont, even in the context of substantial GC dose reductions. CRF1 antagonism may be a promising therapeutic approach for improving reproductive hormones in adults with CAH.*."

Clinical • P3 data • Congenital Adrenal Hyperplasia • Endocrine Disorders • Oncology • Pediatrics

Crinecerfont Maintains Serum Androstenedione Levels with Reduced Glucocorticoid Doses in Adults with Classic Congenital Adrenal Hyperplasia: 1-Year Results from the CAHtalyst™ Adult Study (ENDO 2025) - P3 | "In both periods, GC doses were kept stable for 4 weeks to measure the impact on androgens and then reduced to a target of 8-10 mg/m2/d in hydrocortisone equivalents. In adults with CAH, substantial reductions in A4 and in GC doses were observed with crinecerfont in the DBPC period. By the end of OL treatment, A4 was maintained or improved even in the context of lower, more physiologic GC doses. Thus, crinecerfont not only reduces androgen excess; by enabling GC doses to be lowered, crinecerfont can also reduce the adverse effects of chronic supraphysiologic GC exposure.*."

Clinical • Congenital Adrenal Hyperplasia • Endocrine Disorders • Pediatrics

Crinecerfont Improves Clinical Outcomes in Adults With Classic Congenital Adrenal Hyperplasia: 1-Year Results From the CAHtalyst™ Adult Study (ENDO 2025) - P3 | "Adults with CAH who received up to 1 year of crinecerfont continued to show improvements in BMI and insulin resistance, as expected with lower GC doses. Moreover, despite substantial GC dose reductions, hirsutism in female participants improved with crinecerfont. Given the known adverse effects of ACTH/androgen excess and chronic supraphysiologic GC exposure, these results represent a promising therapeutic advancement in CAH.*."

Clinical • Clinical data • Congenital Adrenal Hyperplasia • Dyslipidemia • Endocrine Disorders

Evaluation of Potential Drug-Drug Interactions with Crinecerfont (ENDO 2025) - "Study 3 (N=25) evaluated the PK of an oral contraceptive (ethinylestradiol/levonorgestrel 30/150 µg) with (Test) or without (Reference) crinecerfont 100 mg. Given the safety profile of crinecerfont, the increase in crinecerfont exposure with ketoconazole was not considered clinically relevant, and no dose adjustments are necessary when administering crinecerfont with CYP3A4 inhibitors. Decreased crinecerfont exposure with rifampin might reduce the efficacy of crinecerfont. Thus, if taken with a strong CYP3A4 inducer, the morning and evening doses of crinecerfont should be increased 2-fold."

Congenital Adrenal Hyperplasia • Endocrine Disorders

Crinecerfont Maintains Adrenocorticotropic Hormone and 17-Hydroxyprogesterone Levels with Reduced Glucocorticoid Doses in Adults with Classic Congenital Adrenal Hyperplasia: 1-Year Results from the CAHtalyst™ Adult Study (ENDO 2025) - P3 | "In both periods, GC doses were kept stable for 4 weeks to measure the impact on androgens and then reduced to a target of 8-10 mg/m2/d in hydrocortisone equivalents. Mean ACTH and 17-OHP were maintained near or below BL in adults with CAH who received up to 1 year of crinecerfont, allowing for substantial reductions in GC dose. Crinecerfont is a non-GC approach for managing excess ACTH and adrenal androgens, enabling GC doses to be lowered and thereby reducing androgens and the adverse effects of chronic supraphysiologic GC exposure.*. .*"

Clinical • Congenital Adrenal Hyperplasia • Endocrine Disorders • Pediatrics

Crinecerfont Reduces Plasma Adrenocorticotropic Hormone and Serum 17-Hydroxyprogesterone Levels in Children and Adolescents with Classic Congenital Adrenal Hyperplasia: 1-Year Results from the CAHtalystTM Pediatric Study (ENDO 2025) - P3 | "In both periods, GC doses were kept stable for the first 4 weeks to measure the impact on androgens and then reduced to a target of 8-10 mg/m2/d in hydrocortisone equivalents while maintaining or improving androstenedione (A4) relative to Day 1 baseline (BL). In children/adolescents with CAH who received up to 1 year of crinecerfont, ACTH and 17-OHP were reduced to below BL levels, even after reductions in GC dose. These decreases were consistent with the significant A4 reduction reported in the DBPC period. Crinecerfont, a novel oral CRF1 antagonist, is a non-GC approach to manage excess ACTH and adrenal androgens in CAH, enabling GC doses to be lowered and thus achieving the dual goals of reducing androgen excess and the risks associated with long-term supraphysiologic GC exposure.*."

Clinical • Congenital Adrenal Hyperplasia • Endocrine Disorders • Pediatrics

Crinecerfont Shows Favorable Trends in Improving Weight-Related Outcomes in Adults With Classic Congenital Adrenal Hyperplasia: 1-Year Results From the CAHtalyst™ Adult Study (ENDO 2025) - P3 | "Adults with CAH who received up to 1 year of crinecerfont showed reductions in BMI and weight. Among participants who were overweight or obese at BL, 30.8% achieved a >5% reduction in weight at Month 12. These analyses indicate that the substantial GC dose reductions enabled by crinecerfont can allow for improvements in the weight-related effects associated with chronic supraphysiologic GC exposure.*."

Clinical • Congenital Adrenal Hyperplasia • Endocrine Disorders • Genetic Disorders • Obesity

Efficacy of Crinecerfont in Reducing Androgen Levels in Congenital Adrenal Hyperplasia: A Meta-Analysis of Randomized Trials (ENDO 2025) - "Further trials are warranted to confirm long-term efficacy and safety.*. .*"

Retrospective data • Congenital Adrenal Hyperplasia • Endocrine Disorders • Pediatrics

Crinecerfont Allows for More Physiologic Glucocorticoid Treatment With Reduction of Androstenedione to a Normal Range in Adults With Classic Congenital Adrenal Hyperplasia: Post Hoc Analyses of the CAHtalyst™ Adult Study (ENDO 2025) - P3 | "GC doses were kept stable for the first 4 weeks to measure the impact on androgens, followed by a planned GC down-titration over 8 weeks to achieve a target dose of 8-10 mg/m2/d in hydrocortisone equivalents (HCe). In CAHtalyst Adult, 63% of participants taking crinecerfont achieved a physiologic GC dose (≤11 mg/m2/d HCe) at Wk24 while maintaining/improving A4. Post hoc analyses showed 82% achieved a physiologic GC dose with crinecerfont regardless of A4 level; of these, 53% had normal A4. In contrast, 37% achieved a physiologic GC dose with placebo, and 49% had elevated A4 despite supraphysiologic GC dosing."

Clinical • Retrospective data • Congenital Adrenal Hyperplasia • Endocrine Disorders • Pediatrics

Crinecerfont Maintains Reductions in Serum Androstenedione Levels and Glucocorticoid Doses in Children and Adolescents with Classic Congenital Adrenal Hyperplasia: 1-Year Results from the CAHtalystTM Pediatric Study (ENDO 2025) - P3 | "In children and adolescents with CAH, reductions in excess A4 and GC doses observed with crinecerfont during the DBPC period were maintained during the OL period. By the end of OL treatment, mean A4 was maintained below BL levels despite a significant reduction in GC dosing to lower, more physiologic doses. Thus, not only can crinecerfont reduce androgen excess, but by enabling GC doses to be lowered, crinecerfont may also reduce the adverse effects of chronic exposure to supraphysiologic GCs over a lifetime of treatment.*."

Clinical • Congenital Adrenal Hyperplasia • Endocrine Disorders • Pediatrics