Adrenal (Excluding Mineralocorticoids)

ORF32-05 - Characterization of Children and Adolescents with Classic CAH WHO Had Slowed Bone Age Progression and Improved Height Prediction with Crinecerfont

Sunday, June 14, 2026

2:25 PM - 2:40 PM CT

Location: Room W184ABC

Oral Abstract Presenter(s)

MV

Maria G. Vogiatzi, MD

Professor of Pediatrics
Children's Hospital of Philadelphia
Gladwyne, PA, United States

Co-Author(s)

MC

Martine Cools, MD, PhD

Ghent University Hospital and Ghent University
Ghent, Belgium
RC

Régis Coutant, MD, MS

CHU d’Angers
Angers, Pays de la Loire, France
AE

Ayca Erkin-Cakmak, MD, MPH

University of California San Francisco and Benioff Children’s Hospital
San Francisco, California, United States
OL

Oksana Lekarev, DO (she/her/hers)

Weill Cornell Medicine
New York, New York, United States
LM

Laetitia Martinerie, MD, PhD

Robert Debré Hospital, APHP, Paris Cité University, and Inserm, Physiologie et Physiopathologie Endocriniennes
Paris, Ile-de-France, France
RN

Ron S. Newfield, MD

Rady Children's Hospital and University of California San Diego
San Diego, California, United States
Kyriakie Sarafoglou, MD

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

Jean L. Chan, MD

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
MK

Mimi S. Kim, MD, MSc

Center for Endocrinology, Diabetes, and Metabolism, Children’s Hospital Los Angeles, University of Southern California
Los Angeles, California, United States

Disclosure(s):

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

Background: In pediatric patients with classic congenital adrenal hyperplasia (CAH), excess androgens cause accelerated bone age (BA) maturation, leading to reduced adult height. Crinecerfont is a first-in-class corticotropin-releasing factor type 1 receptor (CRF1) antagonist that is FDA-approved as an adjunct to glucocorticoid replacement to control androgens in patients (≥4 years old) with classic CAH, including both the salt-wasting and simple virilizing forms. In the crinecerfont phase 3 CAHtalyst™ Pediatric trial (NCT04806451), no overall mean improvements in height prediction or adult height were observed at 2 years. However, most participants were mid-to-late puberty at study entry, with limited growth potential.

Objective: To describe changes in BA advancement and predicted adult height in a subset of growing CAHtalyst Pediatric participants.

Methods: Participants from the 28-week double-blind placebo-controlled period continued crinecerfont (25, 50, or 100 mg BID per weight) or were switched from placebo for the 6-month open-label and ongoing open-label extension periods. Participants with available assessments (BA at baseline < 14 years [females] and < 16 years [males]) who were not on an aromatase inhibitor at baseline were included for post hoc analysis; baseline was defined as the start of crinecerfont treatment. Mean change from baseline in BA minus chronological age (BA-CA) and predicted adult height (assessed using the Bayley-Pinneau method based on BA) were evaluated at Month 24 of the study.

Results: Among the 103 randomized participants, 41 (16 female, 25 male) had available assessments at baseline and Month 24. Baseline characteristics (mean±SD) were: age (9.2±2.4 years), BA (11.0±2.5 years), BA-CA (1.8±2.0 years), and predicted adult height (166±9.6 cm). Among these 41 participants, 26 (63%) had an advanced BA at baseline ≥1 year. At Month 24, for the 26 with advanced BA at baseline, 4 (15%) showed worsening BA advancement (change from baseline BA-CA ≥0.5 years), 8 (31%) showed no change (> -0.5 to < 0.5 years), and 7 (27%) had improvement in BA-CA from 6 months up to 1 year. In addition, 7 (27%) participants had improvement in BA-CA of 1 year or more, with mean±SEM improvements from baseline in predicted adult height observed at Month 24 in these participants (+6.6±1.6 cm).

Conclusion: 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.