crinecerfont (NBI-74788) / Neurocrine, Sanofi - LARVOL DELTA

Endocrinology : what's new in 2024 (PubMed, Rev Med Suisse) - "In this article, we look at a selection of recent developments in various areas of endocrinology. We focus on advances in endocrine pharmacotherapy and endocrine surgery, addressing several areas: a) the thyroid safety of Glucagon-Like Peptide-1 (GLP1) analogues; b) the efficacy of adrenal surgery for mild autonomous cortisol secretion; c) crinecerfont in the management of congenital adrenal hyperplasia in adults and children; d) paltusotin as a novel oral therapy for acromegaly and e) TransCon PTH (palopegteriparatide) as a novel therapy for chronic hypoparathyroidism."

Journal • Acromegaly • Congenital Adrenal Hyperplasia • Endocrine Disorders • Hypoparathyroidism

Future Directions in the Management of Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency. (PubMed, J Clin Endocrinol Metab) - "Circadian delivery of hydrocortisone improves disease management of 21OHD compared to conventional glucocorticoids. Glucocorticoid-sparing therapies such as crinecerfont and atumelnant offer the potential for a block-and-replace strategy, with physiologic replacement dosing of hydrocortisone."

Journal • Review • Congenital Adrenal Hyperplasia • Endocrine Disorders

Innovations in pharmacotherapy of CAH (ESPE 2024) - "Circadian delivery of hydrocortisone improves control of 21OHD compared to conventional hydrocortisone and over time results in lower glucocorticoid exposure...The P450 17A1 inhibitor abiraterone acetate directly blocks androgen production but at the expense of progesterone accumulation. The corticotropin-releasing factor type 1 receptor (CRF1) antagonists crinecerfont and tildacerfont have shown efficacy in suppressing ACTH and adrenal biomarkers in phase 2 trials...Gene therapy is also under study with an AAV5 vector (BBP-631). These modern approaches to deliver cortisol replacement and the suppress adrenal androgen production should simplify management, improve disease control, and mitigate the long-term consequences of 21OHD and chronic non-physiologic glucocorticoid exposure."

Congenital Adrenal Hyperplasia • Endocrine Disorders • Gene Therapies

CRH receptor antagonist crinecerfont - a promising new treatment option for patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. (PubMed, J Pediatr Endocrinol Metab) - "Successful implementation depends on patient adherence and monitoring to avoid possible complications such as adrenal crises. Overall, crinecerfont represents a valuable development, but further research and careful clinical management are needed to optimize its use in CAH treatment."

Journal • Congenital Adrenal Hyperplasia • Endocrine Disorders

Crinecerfont, a Corticotropin-Releasing Factor Type 1 Receptor (CRF1) Antagonist, Reduced Excess Adrenal Androgens and Glucocorticoid Doses in Children and Adolescents with Classic Congenital Adrenal Hyperplasia: Results from CAHtalystTM Pediatric (ESPE 2024) - " Children and adolescents (4-17yrs) with CAH who had stable GC doses >12mg/m2/d in hydrocortisone equivalents (HCe), androstenedione higher than the midpoint of reference range, and 17-hydroxyprogesterone (17-OHP) >2x upper limit of normal (ULN) were randomized (2:1) to crinecerfont (25, 50, or 100mg BID based on weight) or placebo. Crinecerfont, a novel oral CRF1 antagonist, represents a potential treatment option to improve androgen control and reduce supraphysiologic GC dose in pediatric patients with classic CAH. In the largest interventional Phase 3 study conducted to date in CAH, crinecerfont-treated participants experienced decreases in androstenedione and 17-OHP during an initial GC-stable period, enabling a significant reduction of supraphysiologic GC doses by 28wks while maintaining androstenedione control."

Clinical • Congenital Adrenal Hyperplasia • Endocrine Disorders • Pediatrics

Crinecerfont in Adult Congenital Adrenal Hyperplasia. (PubMed, N Engl J Med) - No abstract available

Journal • Congenital Adrenal Hyperplasia • Endocrine Disorders

Crinecerfont in Adult Congenital Adrenal Hyperplasia. Reply. (PubMed, N Engl J Med) - No abstract available

Journal • Congenital Adrenal Hyperplasia • Endocrine Disorders

Crinecerfont in Adult Congenital Adrenal Hyperplasia. (PubMed, N Engl J Med) - No abstract available

Journal • Congenital Adrenal Hyperplasia • Endocrine Disorders

Baseline Characteristics of Adults with Classic Congenital Adrenal Hyperplasia Enrolled in CAHtalyst, a Phase 3 Study of Crinecerfont, a Corticotropin-Releasing Factor Type 1 Receptor Antagonist (AACE 2024) - P3 | "Key eligibility criteria included glucocorticoid dose >13 mg/m 2 /day in hydrocortisone equivalents (HCe; conversion factors: 4x for predni[so]lone, 60x for dexamethasone) adjusted for body surface area (BSA) with stable dose for ≥1 month prior to screening, and normal or elevated androstenedione (A4). Androgens and other steroid biomarkers were elevated despite treatment with supraphysiological doses of glucocorticoids. These findings emphasize the urgent need for novel glucocorticoid-sparing treatments for this chronic condition."

Clinical • P3 data • Cardiovascular • Congenital Adrenal Hyperplasia • Diabetes • Endocrine Disorders • Hypertension • Metabolic Disorders • Obesity • Oncology • Osteoporosis • Rheumatology • Women's Health

Phase 3 Trial of Crinecerfont in Adult Congenital Adrenal Hyperplasia. (PubMed, N Engl J Med) - P3 | "Among patients with CAH, the use of crinecerfont resulted in a greater decrease from baseline in the mean daily glucocorticoid dose, including a reduction to the physiologic range, than placebo following evaluation of adrenal androgen levels. (Funded by Neurocrine Biosciences; CAHtalyst ClinicalTrials.gov number, NCT04490915.)."

Journal • P3 data • Congenital Adrenal Hyperplasia • Endocrine Disorders • Fatigue • Nephrology • Pain • Renal Disease

Phase 3 Trial of Crinecerfont in Pediatric Congenital Adrenal Hyperplasia. (PubMed, N Engl J Med) - P3 | "In this phase 3 trial, crinecerfont was superior to placebo in reducing elevated androstenedione levels in pediatric participants with CAH and was also associated with a decrease in the glucocorticoid dose from supraphysiologic to physiologic levels while androstenedione control was maintained. (Funded by Neurocrine Biosciences; CAHtalyst Pediatric ClinicalTrials.gov number, NCT04806451.)."

Journal • P3 data • Congenital Adrenal Hyperplasia • Endocrine Disorders • Pain • Pediatrics

CAHtalyst Pediatric: Results from the Randomized, Double-Blind, Placebo-Controlled Period of a Phase 3 Trial of Crinecerfont, a Corticotropin-Releasing Factor Type 1 Receptor Antagonist, in Children and Adolescents with Classic Congenital Adrenal Hyperplasia (ENDO 2024) - "Abstract is embargoed at this time."

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

CAHtalyst: Results from the Randomized, Double-Blind, Placebo-Controlled Period of a Phase 3 Trial of Crinecerfont, a Corticotropin-Releasing Factor Type 1 Receptor (CRF1) Antagonist, in Adults with Classic Congenital Adrenal Hyperplasia (ENDO 2024) - "Abstract is embargoed at this time."

Clinical • P3 data • Congenital Adrenal Hyperplasia • Endocrine Disorders

Neurocrine Biosciences (NBIX) Receives Breakthrough Therapy Designation from U.S. Food and Drug Administration for Crinecerfont in Congenital Adrenal Hyperplasia (Streetinsider.com) - "Neurocrine Biosciences, Inc...announced it received Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA) for crinecerfont in congenital adrenal hyperplasia. The Company also provided updates on its R&D portfolio and strategy at its Analyst Day, held in New York....'The outstanding safety and efficacy results from the Phase 3 CAHtalyst™ studies in pediatric and adult patients suggest that crinecerfont has the potential to represent a substantial improvement over current standard of care in CAH by controlling androgen levels and allowing for reduced steroid doses. We remain on track to submit the new drug application in 2024.'"

Breakthrough therapy designation • NDA • Congenital Adrenal Hyperplasia • Genetic Disorders • Rare Diseases

Crinecerfont: “CAHtalystTM adult and pediatric study common endpoints”; Congenital adrenal hyperplasia (Neurocrine Biosciences) - Q3 2023 Results

P3 data • Congenital Adrenal Hyperplasia

Crinecerfont: NDA submission in US for congenital adrenal hyperplasia in adults in 2024 (Neurocrine Biosciences) - Q3 2023 Results: NDA submission in US for congenital adrenal hyperplasia in pediatrics in 2024

NDA • Congenital Adrenal Hyperplasia

Neurocrine Biosciences Reports Third Quarter 2023 Financial Results and Raises 2023 INGREZZA Sales Guidance (PRNewswire) - P3 | N=183 | CAHtalyst (NCT04490915) | Sponsor: Neurocrine Biosciences | "In September 2023, the Company announced positive top-line data from the Phase 3 CAHtalyst^™ clinical study of crinecerfont in adults with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD). The study met its primary as well as important key secondary endpoints...In October 2023, the Company announced positive top-line data from the Phase 3 CAHtalyst clinical study of crinecerfont in pediatrics with CAH due to 21-hydroxylase deficiency (21-OHD). The study met both its primary and key secondary endpoint."

P3 data • Congenital Adrenal Hyperplasia

Crinecerfont in a First Clinical Application of a CRH Antagonist: Further Potential Uses are still an Open Chapter! (PubMed, J Clin Endocrinol Metab) - No abstract available

Journal

Response to Crinecerfont Treatment in Adolescents with Classic Congenital Adrenal Hyperplasia Is Correlated with Elevated Baseline Hormone Concentrations but Not Glucocorticoid Dose (ESPE 2023) - No abstract available

Endocrine Disorders

Current and future perspectives on clinical management of classic 21-hydroxylase deficiency. (PubMed, Endocr J) - "In this review, we aimed to comprehensively summarize the current status of classic 21OHD treatment, including the initial treatment during the neonatal period, management of adrenal insufficiency, maintenance therapy of each life stage, and the importance of clinical management as DSD for 46,XX female patients. The recently developed agents, Chronocort, and Crinecerfont, are also discussed."

Journal • Cardiovascular • Endocrine Disorders • Genetic Disorders • Hypertension • Infertility • Nephrology • Obesity • Osteoporosis • Renal Disease • Rheumatology • Sexual Disorders

Crinecerfont, a CRF1 Receptor Antagonist, Lowers Adrenal Androgens in Adolescents with Congenital Adrenal Hyperplasia. (PubMed, J Clin Endocrinol Metab) - P2 | "Adolescents with classic 21OHD CAH had substantial reductions in adrenal androgens and androgen precursors after 14 days of oral crinecerfont administration. These results are consistent with a study of crinecerfont in adults with classic 21OHD CAH."

Journal • Endocrine Disorders

Global Safety and Efficacy Registration Study of Crinecerfont in Pediatric Patients With Classic Congenital Adrenal Hyperplasia (CAHtalyst Pediatric Study) (clinicaltrials.gov) - P3 | N=103 | Active, not recruiting | Sponsor: Neurocrine Biosciences | Trial primary completion date: Aug 2023 ➔ Mar 2023

Trial primary completion date • Endocrine Disorders • Pediatrics

Global Safety and Efficacy Registration Study of Crinecerfont in Pediatric Patients With Classic Congenital Adrenal Hyperplasia (CAHtalyst Pediatric Study) (clinicaltrials.gov) - P3 | N=103 | Active, not recruiting | Sponsor: Neurocrine Biosciences | Recruiting ➔ Active, not recruiting

Enrollment closed • Endocrine Disorders • Pediatrics

CAHtalyst: Global Safety and Efficacy Registration Study of Crinecerfont for Congenital Adrenal Hyperplasia (clinicaltrials.gov) - P3 | N=182 | Active, not recruiting | Sponsor: Neurocrine Biosciences | Recruiting ➔ Active, not recruiting

Enrollment closed • Endocrine Disorders

Global Safety and Efficacy Registration Study of Crinecerfont in Pediatric Patients With Classic Congenital Adrenal Hyperplasia (CAHtalyst Pediatric Study) (clinicaltrials.gov) - P3 | N=81 | Recruiting | Sponsor: Neurocrine Biosciences | Trial completion date: Apr 2024 ➔ Aug 2027 | Trial primary completion date: Apr 2023 ➔ Aug 2023

Trial completion date • Trial primary completion date • Endocrine Disorders • Pediatrics