Neurocrine Biosciences,has announced that the U.S. Food and Drug Administration (FDA) has approved CRENESSITY™ (crinecerfont) capsules and oral solution for use as an adjunctive treatment to glucocorticoid replacement in adults and pediatric patients aged four years and older with classic congenital adrenal hyperplasia (CAH). CAH is a rare, serious genetic condition that affects the adrenal glands, leading to an overproduction of androgens. CRENESSITY is the first and only treatment specifically designed to target the underlying cause of this condition by directly reducing excess adrenocorticotropic hormone (ACTH) and adrenal androgen production, allowing for a reduction in glucocorticoid doses. This approval marks a significant breakthrough in the treatment of classic CAH.
“For more than 30 years, Neurocrine Biosciences has been pioneering research on the role of corticotropin-releasing factor and its receptor, CRF1, in the development of congenital adrenal hyperplasia,” said Kyle W. Gano, Ph.D., CEO of Neurocrine Biosciences. “The approval of CRENESSITY is a milestone for the CAH community, and we are grateful to all the patients, families, caregivers, and clinical investigators who contributed to this journey and helped bring this new therapy to market.”
Dina Matos, Executive Director of the CARES Foundation, added, “Managing CAH with high-dose steroids is challenging for many patients and families, as it can affect quality of life. This new medication offers a promising option to reduce excess adrenal androgens and decrease the reliance on high-dose steroids, improving the overall treatment experience for those living with CAH.”
CRENESSITY will be commercially available within approximately one week, distributed through PANTHERx Rare, a specialty pharmacy, to streamline prescription fulfillment. Neurocrine Biosciences also offers a comprehensive assistance program, Neurocrine Access Support, which provides resources for patients, caregivers, and healthcare providers to navigate insurance and access financial support, with most patients paying $10 or less per month for the medication.
The approval is supported by the largest-ever clinical trial program for classic CAH, known as the CAHtalyst Pediatric and Adult Phase 3 global registrational studies. Results from the CAHtalyst Phase 3 trials were published in The New England Journal of Medicine and demonstrate the efficacy and safety of CRENESSITY in reducing adrenal androgen production and enabling lower glucocorticoid doses.
Dr. Richard Auchus, Professor at the University of Michigan Health and Principal Investigator for the studies, commented, “Chronic treatment with high-dose glucocorticoids can lead to serious health issues such as obesity, hypertension, and osteoporosis. The ability to reduce glucocorticoid doses to more physiologic levels, while controlling androgen levels, offers substantial benefits for CAH patients.”
Phase 3 CAHtalyst Pediatric Study:
In the pediatric phase of the study, CRENESSITY significantly reduced androstenedione levels at Week 4 compared to placebo, which showed an increase in androgen levels. By Week 28, children on CRENESSITY achieved significant reductions in glucocorticoid doses while maintaining or improving androgen control. Children on CRENESSITY showed approximately four times greater reductions in androstenedione and steroid dose compared to those on placebo, and around 12 times greater reductions in 17-hydroxyprogesterone (17-OHP). The most common side effects were mild to moderate and included headache, abdominal pain, fatigue, nasal congestion, and nosebleeds.
Phase 3 CAHtalyst Adult Study:
In adults, CRENESSITY demonstrated significant reductions in glucocorticoid doses at Week 24 while maintaining or improving androstenedione levels. A significantly higher percentage of patients (63%) on CRENESSITY achieved a more physiologic glucocorticoid dose compared to just 18% on placebo. Additionally, patients on CRENESSITY showed eight times greater reductions in androstenedione and 37 times greater reductions in 17-OHP compared to placebo. The most common side effects in adults included fatigue, headache, dizziness, joint pain, and muscle pain, with most side effects being temporary and mild to moderate.
Safety Profile and Considerations:
Both pediatric and adult studies indicated that CRENESSITY was well tolerated, with no treatment-related serious adverse events reported. However, adrenal insufficiency and crisis are risks associated with CAH and can occur if glucocorticoid doses become too low. In the pediatric study, there were no cases of adrenal crisis, while in the adult study, two patients (1.6%) on CRENESSITY experienced adrenal crisis, compared to none on placebo. Healthcare providers should carefully manage glucocorticoid dosing when using CRENESSITY.
The approval of CRENESSITY is a major advancement for the CAH community, providing a new therapeutic option that reduces the need for high-dose steroids, addresses adrenal androgen overproduction, and improves the management of a chronic, life-altering condition.
