Crenessity (crinecerfont) / Neurocrine Biosciences, Sanofi - LARVOL DELTA

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Crinecerfont in Participants With Classic Congenital Adrenal Hyperplasia (CAH) Who Are Less Than 4 Years Old (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Neurocrine Switzerland GmbH | Initiation date: Apr 2026 ➔ Jul 2026 | Not yet recruiting ➔ Recruiting

Enrollment open • Trial initiation date • Congenital Adrenal Hyperplasia • Endocrine Disorders • Pediatrics

Sustained Glucocorticoid Reductions and Improved Clinical Outcomes with Up to 2 Years of Crinecerfont in Children and Adolescents with Classic Congenital Adrenal Hyperplasia (ESPE 2026) - No abstract available

Clinical • Clinical data • Congenital Adrenal Hyperplasia • Endocrine Disorders

Sustained ACTH and 17-Hydroxyprogesterone Reductions and Improved Clinical Outcomes With Up to 2 Years of Crinecerfont in Pediatric Patients with Classic Congenital Adrenal Hyperplasia (ESPE 2026) - No abstract available

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

The evolution of new approaches to the treatment of congenital adrenal hyperplasia. (PubMed, Endocr Rev) - "Circadian delivery of hydrocortisone with modified-release preparations or continuous subcutaneous infusion achieves better control at the same or lower daily dose than hydrocortisone tablets. GC-sparing therapies, the first being the corticotropin-releasing factor type 1 receptor antagonist crinecerfont, offer a block-and-replace approach, with near-physiologic dosing of GCs and a second agent to reduce precursor accumulation. The melanocortin type 2 (ACTH) receptor antagonist atumelnant and the anti-ACTH antibody asedebart are in trials. This article reviews the historical background, genetics, pharmacology, and data supporting the use of alternative strategies, as well as the practical implications and limitations of these approaches in routine patient care. A new era of CAH management has arrived, and we provide a perspective on the path forward using new tools to address the remaining unsolved challenges."

Journal • Congenital Adrenal Hyperplasia • Endocrine Disorders

Characterization of Children and Adolescents With Classic CAH Who Had Slowed Bone Age Progression and Improved Height Prediction With Crinecerfont (ASBMR 2026) - No abstract available

Clinical

Bone Outcomes in Adults With Classic Congenital Adrenal Hyperplasia Treated With Crinecerfont For Up to 2 Years in CAHtalyst® Adult Study (ASBMR 2026) - No abstract available

Clinical • Congenital Adrenal Hyperplasia • Endocrine Disorders

Characterization of Children and Adolescents With Classic CAH Who Had Slowed Bone Age Progression and Improved Height Prediction With Crinecerfont (ASBMR 2026) - No abstract available

Clinical

Crinecerfont: emerging role in the management of congenital adrenal hyperplasia. (PubMed, Expert Rev Endocrinol Metab) - "Recent Phase 2 and Phase 3 trials have demonstrated promising efficacy and safety across adult, adolescent, and pediatric populations. Crinecerfont may represent a promising adjunctive therapy in CAH management, addressing both biochemical control as well as quality of life and potentially long-term outcomes."

Journal • Review • Congenital Adrenal Hyperplasia • Endocrine Disorders • Pediatrics

Pharmacotherapeutic strategies for the management of congenital adrenal hyperplasia. (PubMed, Expert Opin Pharmacother) - "Future management will likely involve combination pharmacotherapies directed at the hypothalamic axis. Eventual use of CYP21A2 gene therapies may offer disease modification."

Journal • Review • Congenital Adrenal Hyperplasia • Endocrine Disorders • Gene Therapies • CYP1A2 • CYP21A2

SI03-06 - Redefining Classic CAH Treatment (ENDO 2026) - "Dr. Wenyu Huang will be presenting "Redefining Classic CAH Treatment" which explores findings from the CAHtalyst™ study, which evaluated outcomes in patients taking Crenessity® (crinecerfont)."

Long-Term Crinecerfont Enables Sustained Decreases in Glucocorticoid Doses and Improves Clinical Outcomes in Children and Adolescents with Classic Congenital Adrenal Hyperplasia: 2-Year Results from Cahtalyst™ Pediatric (ENDO 2026) - P3 | "In children and adolescents with CAH, treatment with crinecerfont enabled substantial reductions in GC dose that were sustained for up to 2 years. Improvements were also observed in clinical outcomes related to long-term supraphysiologic GC exposure, including BMI and insulin resistance. Crinecerfont is a well-tolerated treatment that, by enabling sustained GC dose reductions, may reduce cardiometabolic risk in patients with CAH."

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

Crinecerfont Improved Biochemical Control in All Treated Patients with Congenital Adrenal Hyperplasia in Our Cohort, While the Possibility of Dose Reduction Depended on Baseline Control. (ENDO 2026) - "Crinecerfont. improved biochemical control in all patients with classical CAH in our cohort. Crinecerfont enabled normalization of biochemical control and clinically meaningful glucocorticoid dose reductions in patients with good and moderate baseline disease control."

Clinical • Congenital Adrenal Hyperplasia • Endocrine Disorders

Crinecerfont Improves Weight-Related Outcomes and Insulin Resistance in Adults with Classic Congenital Adrenal Hyperplasia: 2-Year Results from the CAHtalyst™ Adult Study (ENDO 2026) - P3 | " The 182 randomized participants had a baseline mean daily GC dose of 17.6 mg/m2/d (32.3 mg/d) hydrocortisone equivalents (HCe). Adults with CAH who received up to 2 years of crinecerfont achieved and maintained reductions in GC dose, accompanied by favorable changes in weight, body composition, and IR. These results suggest that crinecerfont can reduce the risk of cardiometabolic complications associated with long-term supraphysiologic GC treatment."

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

A Cross-Sectional Survey on Crinecerfont and Quality of Life of Adults with Classic Congenital Adrenal Hyperplasia (CAH) in the United States (US) Participating in Cahtalyst Adult Open-Label Extension (OLE) Study (ENDO 2026) - P3 | "While possible attrition, recall, and nonresponse bias should be acknowledged, these findings suggest crinecerfont as an adjunct treatment to manage CAH may lead to meaningful improvements in patients' perceived lived experiences."

Clinical • HEOR • Congenital Adrenal Hyperplasia • Endocrine Disorders

Bone Outcomes in Adults with Classic Congenital Adrenal Hyperplasia Treated with Crinecerfont for Up to 2 Years in Cahtalyst™ Adult Study (ENDO 2026) - P3 | " At baseline, the 182 randomized participants had a median age of 29.5 years (range: 18-58) and mean GC dose of 17.6 mg/m2/d (32.3 mg/d) hydrocortisone equivalents; mean (±SD) BMD z-scores were below 0 (lumbar spine, -0.29±1.4; hip, -0.21±1.1). Adults with CAH who received up to 2 years of crinecerfont had a mean 38% reduction in observed GC dose. All bone turnover markers trended towards improvement from baseline to Month 12. Markers of bone formation remained at similar levels at Month 18 while markers of bone resorption (CTx, NTx) showed a decreasing trend."

Clinical • Congenital Adrenal Hyperplasia • Endocrine Disorders • Musculoskeletal Diseases • Orthopedics

Treat the Patient and Not the ACTH: Balancing Hormonal Control and Clinical Outcomes in Classic Congenital Adrenal Hyperplasia (ENDO 2026) - "Upon returning to our institute, fludrocortisone was resumed, daily glucocorticoid dosage was up titrated and switched to prednisone, Crenessity was initiated with the goal of tapering glucocorticoid regimen in the future, and he was educated on importance of following sick day rules to prevent adrenal crisis. Attempts to suppress ACTH may lead to glucocorticoid overtreatment, unnecessary diagnostic testing, and patient distress as in this case. In the management of classic CAH, we reinforce that medication should be titrated by assessing the entire clinical picture and all patients with classic CAH may require fludrocortisone therapy."

Clinical • Clinical data • Late-breaking abstract • CNS Disorders • Congenital Adrenal Hyperplasia • Endocrine Disorders • Hypotension • Mood Disorders • Nephrology • Renal Disease

Pharmacokinetics, Safety and Tolerability of Crinecerfont in Participants With Congenital Adrenal Hyperplasia Who Are Less Than 2 Years Old (clinicaltrials.gov) - P2 | N=7 | Active, not recruiting | Sponsor: Neurocrine Biosciences | Recruiting ➔ Active, not recruiting

Enrollment closed • Congenital Adrenal Hyperplasia • Endocrine Disorders • Pediatrics

Significant Heterogeneity in Hormonal Control in Classical Congenital Adrenal Hyperplasia Highlights the Limitations of Standard Glucocorticoid Dosing. (ENDO 2026) - "These findings support the importance of individualizing treatment, not only by dose escalation. Non-glucocorticoid therapy such as Crinecerfont can be an effective adjunctive approach by decreasing ACTH-mediated androgen production."

Heterogeneity • Congenital Adrenal Hyperplasia • Endocrine Disorders

Crinecerfont Treatment of Classic Congenital Adrenal Hyperplasia Due to 11Β-Hydroxylase Deficiency: A Case Series (ENDO 2026) - "Two months after starting crinecerfont 100 mg BID, DOC was normal ( < 16 ng/dL), blood pressure was improved, and spironolactone was discontinued. Case 4, a 24-YO male, required hydrocortisone 10 mg TID, prednisolone 1 mg/d at bedtime, eplerenone 50 mg BID, and amlodipine 10 mg/d for hypertension... Patients with classic CAH due to 11OHD had improved hormone levels following initiation of crinecerfont; adult patients also had improved blood pressure. This series provides evidence of efficacy for crinecerfont treatment in patients with this rare and challenging form of classic CAH."

Clinical • Cardiovascular • Congenital Adrenal Hyperplasia • Endocrine Disorders • Hypertension

Successful Management of Hypertension in Classic Congenital Adrenal Hyperplasia Due to 17-Hydroxylase Deficiency with Crinecerfont: A Case Report (ENDO 2026) - "Glucocorticoid regimens included hydrocortisone 17.5 mg/day in three divided doses until age 17, dexamethasone 0.25 mg daily for 2 years to simplify tapering, complicated by Cushingoid features, and prednisone, with persistent mineralocorticoid excess...Despite maximal antihypertensive therapy-including spironolactone 600 mg/day, carvedilol, valsartan, and HCTZ-blood pressure remained uncontrolled (150s/120s)...CRF1 receptor antagonists may represent a promising adjunct for difficult-to-control cases, reducing mineralocorticoid excess and improving long-term outcomes. Crinecerfont may expand therapeutic options beyond 21OHD, addressing unmet needs in rare CAH subtypes."

Case report • Clinical • Cardiovascular • Congenital Adrenal Hyperplasia • Endocrine Disorders • Hypertension

Adults with Classic Congenital Adrenal Hyperplasia Taking Crinecerfont Demonstrated Sustained Decreases in Glucocorticoid Doses: 2-Year Results from the Cahtalyst™ Adult Study (ENDO 2026) - P3 | "Adults with CAH taking crinecerfont, a novel CRF1 antagonist recently approved for androgen control for patients with CAH, had substantial reductions in GC doses that were maintained for up to 2 years, with more than two-thirds of participants achieving a GC dose in the physiologic range. Crinecerfont is a well-tolerated treatment option for patients with CAH to reduce chronic supraphysiologic GC exposure, which might improve long-term outcomes."

Clinical • Congenital Adrenal Hyperplasia • Endocrine Disorders

Characterization of Children and Adolescents with Classic CAH WHO Had Slowed Bone Age Progression and Improved Height Prediction with Crinecerfont (ENDO 2026) - P3 | "A substantial proportion of youth with CAH and advanced BA who were treated with crinecerfont for up to 2 years in the CAHtalyst Pediatric trial experienced slowed BA advancement and improved predicted adult height. The percentage of patients with improvement in BA advancement is higher than might be expected based on the natural history of CAH, in which continued worsening of BA advancement is often observed."

Clinical • Congenital Adrenal Hyperplasia • Endocrine Disorders

Use of Crinecerfont in Non-Classical 3 Beta CAH, Case Report. (ENDO 2026) - "Case: Currently 11 yo female with history of Hypothyroidism, on levothyroxinesince since age 2...She was found to have elevation of 17OH Pregnenolone 17 OH Pregnenolone, Serum, MS 272 ng/dL High Reference Range: 6 - 9y: 10 - 186 17-OH Progesterone LCMS 60 ng/dL 0-90 Dehydroepiandrosterone (DHEA) 146 ng/dL High 0-110 Androstenedione LCMS 30 ng/dL Age Female 2 - 8 years 0 - 67 Estradiol < 5 FSH 2.8 mIU/m LH < 0.3 mIU/mL Aldosterone 5.2 ng/dL 5.0-80.0 Renin Activity, Plasma 0.734 ng/mL/hr 0.500-5.900 02 Aldos/Renin Ratio 7.1 0.0-30.0 Normal Insulin and Peptide...She has hydrocortisone on hands... crinecerfont can be of value for non classical 3Beta CAH to potentially reduce hyperandrogegism and if started early enough-premature pubarche. In our case it may not have slowed the pubertal progression, but prevented hyperandrogenic symptoms. Careful monitoring has to be done for signs of AI."

Case report • Clinical • Congenital Adrenal Hyperplasia • Endocrine Disorders • Metabolic Disorders • Nephrology • Renal Disease

Biochemical and Metabolic Improvements with Crinecerfont in Simple Virilizing Congenital Adrenal Hyperplasia (ENDO 2026) - "Case Presentation: A 24-year-old male with simple virilizing CAH (diagnosed age 9) and comorbid attention-deficit/hyperactivity disorder, autism spectrum disorder, and obstructive sleep apnea was maintained on hydrocortisone 40 mg/day (25-10-5 mg dosing) with good medication adherence. (2) Upstream corticotropin-releasing hormone receptor antagonism may enable subsequent glucocorticoid dose reduction while maintaining biochemical targets, offering a novel adjunctive strategy. (3) Weight loss and metabolic improvements occurred despite concurrent glucocorticoid dose increase, suggesting crinecerfont's potential to mitigate cardiometabolic complications independent of glucocorticoid reduction, though causality requires longer follow-up."

ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Autism Spectrum Disorder • CNS Disorders • Congenital Adrenal Hyperplasia • Dyslipidemia • Endocrine Disorders • Genetic Disorders • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Long-Term Crinecerfont Treatment Reduced ACTH and 17-Hydroxyprogesterone and Improved Clinical Outcomes in Children and Adolescents with Classic Congenital Adrenal Hyperplasia: 2-Year Results from Cahtalyst™ Pediatric (ENDO 2026) - P3 | "In pediatric patients with CAH, crinecerfont enabled substantial reductions in ACTH and 17-OHP that were sustained for up to 2 years, despite reductions in GC doses. Moreover, improvements were observed in outcomes related to excess androgens (e.g., acne, hirsutism) among participants with these conditions at baseline. Crinecerfont addresses both treatment goals of decreasing androgens and reducing exposure to chronic supraphysiologic GC doses in patients with CAH, which can translate to improved clinical outcomes."

Clinical • Clinical data • Acne Vulgaris • Congenital Adrenal Hyperplasia • Endocrine Disorders • Pediatrics