Crinecerfont Shows 2-Year Benefits for Weight, Insulin Resistance, and Bone Age in CAH

Long-term treatment with crinecerfont, a selective corticotropin-releasing factor type 1 receptor antagonist, is associated with improved cardiometabolic health in adults and stabilized bone age in pediatric patients with classic congenital adrenal hyperplasia (CAH). Two-year data presented at the ENDO 2026 annual meeting demonstrate that the medication allows for reduced glucocorticoid dosing while maintaining androgen control, addressing a significant challenge in managing this chronic condition.

Cardiometabolic Outcomes in Adults

Crinecerfont (Crenessity) therapy over two years led to measurable improvements in weight, body mass index (BMI), and insulin resistance among adults with classic CAH. According to findings presented by Oksana Hamidi, DO, MSCS, of the UT Southwestern Medical Center, participants experienced a mean weight reduction of 1.7 kg and a BMI decline of 0.7 kg/m² across the study cohort.

The data, derived from the CAHtalyst trial, are particularly significant for patients with metabolic comorbidities. Among participants who entered the study with overweight or obesity, the mean BMI reduction was 0.9 kg/m². Furthermore, 43% of participants who initially presented with insulin resistance reached a state of insulin sensitivity by the two-year mark. Researchers observed a favorable shift in body composition, characterized by a decrease in percent fat mass and a concurrent increase in percent lean mass. These outcomes were achieved alongside the primary clinical goal of reducing supraphysiologic glucocorticoid doses, which are traditionally required for androgen suppression but are linked to long-term metabolic complications.

Bone Age Progression in Pediatric Patients

In pediatric populations, the primary clinical concern regarding CAH is accelerated bone maturation, which can restrict final adult height. Maria G. Vogiatzi, MD, of the Children’s Hospital of Philadelphia, presented two-year data from the CAHtalyst Pediatric trial showing that crinecerfont helps stabilize bone age progression.

For the 41 participants assessed, the mean predicted adult height increased by 4.7 cm among a subset of patients who showed a reduction of more than two standard deviations in bone age. The study found that bone age standard deviation scores (SDS) remained stable or improved in the majority of children with advanced bone age at baseline. By reducing the reliance on high-dose glucocorticoids—which can negatively impact growth—crinecerfont offers a mechanism to address the hormonal drivers of abnormal bone maturation.

Clinical Implications for CAH Management

The results from the CAHtalyst programs suggest a shift in how clinicians may approach the dual goals of hormonal control and long-term health in CAH patients. Historically, managing CAH required a delicate balance between providing enough glucocorticoid to suppress adrenal androgens and avoiding the side effects of chronic steroid exposure, such as weight gain, metabolic syndrome, and growth impairment.

According to trial data, crinecerfont was generally well-tolerated, with over 80% of randomized participants completing the two-year treatment period. The incidence of adrenal insufficiency or crisis remained low, and few participants discontinued treatment due to adverse events. These findings suggest that by decoupling androgen control from high-dose glucocorticoid therapy, patients may experience improved long-term health trajectories.

Summary of Clinical Findings

Data sourced from presentations by Hamidi O, et al., and Vogiatzi MG, et al., at the ENDO 2026 annual meeting.