Adrenal (Excluding Mineralocorticoids)

SUN-465 - 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

Sunday, June 14, 2026

9:00 AM - 4:00 PM CT

Location: ENDOExpo; Poster Floor

Abstract Poster Presenter(s)

Kyriakie Sarafoglou, MD

Professor
University of Minnesota Medical School
Minneapolis, MN, United States

Co-Author(s)

CB

Claire Bouvattier, MD

Rare Developmental Variations of Genitalia National Center, Bicêtre Hospital, Paris Saclay University
Le Kremlin Bicêtre, Ile-de-France, France
DC

Donatella Capalbo, MD, PhD

University of Naples Federico II
Napoli, Campania, Italy
AC

Amy Clark, DO

Saint Louis University School of Medicine, SSM Health Cardinal Glennon Children’s Hospital
St Louis, Missouri, United States
MD

Mehul Tulsidas Dattani, MBBS MD DCH FRCP FRCPCH

UCL Institute of Child Health, United States
EF

Eric I. Felner, MD, MS

Professor of Pediatrics
Emory University School of Medicine
Atlanta, Georgia, United States
MG

Mitchell E. Geffner, MD

The Saban Research Institute of Children’s Hospital Los Angeles and Keck School of Medicine of the University of Southern California
Los Angeles, California, United States
YH

Yeouching Hsu, MD

Northwell Health
New Hyde Park, New York, United States
ML

Maya Lodish, MD

University of California, San Francisco
San Francisco, California, United States
KL

Karen Loechner, MD

Department of Pediatrics, University of Connecticut School of Medicine
Farmington, Connecticut, United States
AM

Artur Mazur, PhD

Medical College of Rzeszow University
Rzeszów, Podkarpackie, Poland
MY

Ming Yang, MD

UT Southwestern Medical Center
Dallas, Texas, United States
JC

Jean L. Chan, MD

Neurocrine Biosciences, Inc.
San Diego, California, United States
RF

Robert H. Farber, PhD

Vice President, Clinical Development
Neurocrine Biosciences, Inc.
San Diego, California, United States
GJ

George S. Jeha, MD

Neurocrine Biosciences, Inc.
San Diego, California, United States
SK

Sanjay Keswani, MD

Neurocrine Biosciences, Inc.
San Diego, California, United States
RM

Rachel Manahan, PhD

Neurocrine Biosciences, Inc.
San Diego, California, United States
ER

Eiry Roberts, MD

Neurocrine Biosciences, Inc.
San Diego, California, United States
JS

Julia Sturgeon, MS

Neurocrine Biosciences, Inc.
San Diego, California, United States
PS

Phyllis W. Speiser, MD

Cohen Children's Medical Center of NY, Feinstein Institute, Northwell Health, Zucker School of Medicine
New Hyde Park, New York, United States

Disclosure(s):

Kyriakie Sarafoglou, MD: Neurocrine Biosciences: Consultant (), Grant Recipient ()

Background: Crinecerfont is a first-in-class corticotropin releasing factor type 1 receptor (CRF1) antagonist that is FDA-approved as an adjunct to glucocorticoid (GC) replacement to control androgens in patients 4 years of age and older with classic congenital adrenal hyperplasia (CAH), including both salt-wasting and simple virilizing forms. During the 6-month double-blind placebo-controlled (DBPC) period of the phase 3 CAHtalyst™ Pediatric trial (NCT04806451), significant reductions in excess ACTH and androgen concentrations were observed with crinecerfont versus placebo, enabling subsequent reductions in GC doses that were previously demonstrated to be sustained through 1 year of crinecerfont treatment.

Objective: To evaluate changes in GC doses and clinical outcomes related to GC exposure in pediatric patients with CAH who received up to 2 years of crinecerfont.

Methods: Participants with CAH due to 21-hydroxylase deficiency who completed 1 year of treatment in the DBPC and open-label periods continued taking crinecerfont (25, 50, or 100 mg BID based on weight) in an ongoing open-label extension (OLE). Mean percent change from baseline in GC dose was assessed at Month 12 and Month 24. Mean change from baseline in outcomes related to GC exposure (e.g., body mass index [BMI], homeostatic model assessment of insulin resistance [HOMA-IR]) were analyzed at Month 12 and Month 24.

Results: Of the 93 participants who entered the OLE, 86 (92%) completed treatment through Month 24. At baseline, mean GC dose was 16.4 mg/m2/d; mean BMI SDS and HOMA-IR were elevated (1.2 and 3.0, respectively). At Month 12, mean GC doses were reduced from baseline (percent change from baseline, -17%; observed mean dose, 13.4 mg/m2/d); these reductions were sustained at Month 24 (percent change from baseline, -17%; observed mean dose, 13.2 mg/m2/d). Mean reductions from baseline in BMI SDS observed at Month 12 were sustained through Month 24 (change from baseline at Month 12, -0.07; Month 24, -0.08), and 15% (7/48) of participants who were overweight/obese at baseline (BMI ≥85th percentile) achieved a normal BMI ( < 85th percentile) at Month 24. Mean reductions from baseline in HOMA-IR at Month 12 were sustained at Month 24 (Month 12, -0.9; Month 24, -0.6). Crinecerfont was well tolerated, and no new safety signals were observed during long-term treatment.

Conclusion: 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.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*