Neurocrine Biosciences has initiated a Phase 2 trial of CRENESSITY (crinecerfont) in children aged 3 months to under 4 years with classic congenital adrenal hyperplasia, supporting plans to expand the therapy’s U.S. indication to younger patients.
Written By: Nalam Karthik, PharmD
Reviewed By: Pharmacally Editorial Team
Neurocrine Biosciences has initiated a Phase 2 clinical trial evaluating the safety and tolerability of crinecerfont (CRENESSITY®) in children aged 3 months to under 4 years with classic congenital adrenal hyperplasia (CAH). The open-label study is intended to generate data supporting a supplemental New Drug Application (sNDA) to extend the therapy’s U.S. approval to younger pediatric patients, who currently have no approved treatment options beyond glucocorticoid replacement.
Crinecerfont received U.S. approval in 2024 as an adjunct to glucocorticoid therapy for adults and children aged 4 years and older with classic CAH. The therapy represented the first major pharmacological advance for the disease in more than seven decades by targeting the underlying hormonal pathway rather than relying solely on supraphysiologic glucocorticoid dosing.
Addressing an unmet need in infants with classic CAH
Classic CAH is a rare inherited endocrine disorder caused by enzyme deficiencies that impair cortisol production and, in many patients, aldosterone synthesis. The resulting increase in adrenocorticotropic hormone (ACTH) drives excessive adrenal androgen production, leading to abnormal growth, virilization, fertility complications, and potentially life-threatening adrenal crises beginning in infancy.
Current management depends on lifelong glucocorticoid replacement. However, doses high enough to suppress ACTH often exceed physiological requirements, exposing patients to long-term complications including obesity, diabetes, cardiovascular disease, osteoporosis, impaired growth, and neuropsychological effects. No therapies are currently approved specifically to reduce androgen excess in children younger than four years.
Crinecerfont is a selective oral corticotropin-releasing factor type 1 (CRF1) receptor antagonist that lowers ACTH secretion at its source in the pituitary gland. By reducing excess ACTH through a non-glucocorticoid mechanism, the therapy helps control adrenal androgen production while allowing lower, more physiological glucocorticoid replacement doses.
Phase 2 study evaluates safety in very young children
The Phase 2 study will enroll 20 children aged 3 months to under 4 years with classic CAH. The open-label, single-arm trial includes a 24-week treatment period, with the primary objective of evaluating the safety and tolerability of crinecerfont in this age group.
Secondary endpoints include characterization of the drug’s pharmacokinetic profile and assessment of pharmacodynamic effects on hormone biomarkers associated with disease control. Neurocrine is conducting the study under an FDA Pediatric Written Request, reflecting regulatory interest in expanding treatment options for younger patients with rare endocrine disorders.
In parallel, the company has completed target enrollment in a separate Phase 2 study in the European Union evaluating crinecerfont in children from birth to under 2 years of age, further broadening its pediatric development program.
Expanding access to disease-modifying therapy
Commenting on the study initiation, Dr. Sanjay Keswani, Chief Medical Officer at Neurocrine Biosciences, said infants and young children with classic CAH often require prolonged exposure to supraphysiologic glucocorticoids during critical stages of growth and development. He noted that evaluating crinecerfont in this population reflects the company’s effort to reduce long-term steroid exposure while helping control disease-related androgen excess.
If the trial confirms an acceptable safety profile and expected pharmacologic activity, Neurocrine plans to submit an sNDA to expand CRENESSITY’s U.S. indication to include patients younger than four years. Such an approval would extend the first non-glucocorticoid therapy for classic CAH to the youngest patients and could reshape early disease management by reducing dependence on high-dose steroid therapy during infancy and early childhood.
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About the Writer
Nalam Karthik (LinkedIn) is a healthcare writer and PharmD graduate with interests in pharmacovigilance, drug safety, clinical data analysis, and quality assurance. He is passionate about translating clinical and pharmaceutical knowledge into accessible healthcare content while staying engaged with advancements in drug development and patient safety initiatives.