FDA Approves Crinecerfont for Congenital Adrenal Hyperplasia in Adults and Children in Landmark Decision

The FDA has approved crinecerfont (Crenessity; Neurocrine Biosciences) for treatment of congenital adrenal hyperplasia (CAH) in adults and children aged 4 years and older, marking the first new therapy for the endocrine disorder in 70 years, according to a Neurocrine Biosciences press release.¹

Crinecerfont is a first-in-class selective corticotropin-releasing factor type 1 (CRF-1) receptor antagonist that reduces excess adrenal androgens for people with CAH due to 21-hyroxylase deficiency. The drug, which will be available as capsules and oral solution and is indicated as adjunctive treatment to glucocorticoid (GC) replacement therapy for adults and children with classic CAH, is expected to be commercially available in approximately 1 week, Neurocrine said.¹

The FDA had previously granted crinecerfont Fast Track, Breakthrough Therapy, Orphan Drug and Priority Review designations.

"Patients and families struggle to achieve balance between managing the symptoms of CAH and the side effects or complications of treatment with high-dose steroids, which may impact quality of life," Dina Matos, executive director of the CARES Foundation. "We are grateful to Neurocrine Biosciences for engaging with our community throughout the drug development process to understand our needs and ultimately providing this new medication that can help reduce excess adrenal androgens and the need for high-dose steroid treatment for individuals living with CAH."¹

The phase 3 CAHtalyst clinical trial program that led to the FDA's decision was the largest to date of children and adults with classic CAH, according to Neurocrine. Findings from the CAHtalyst Pediatric² and CAHtalyst Adult³ Phase 3 global registrational studies were published in The New England Journal of Medicine. In both CAHtalyst studies, participants treated with crinecerfont saw reductions in supraphysiologic GC therapy and reduced androgen levels while maintaining androstenedione control.¹

"The clinical results across both CAHtalyst studies support the efficacy and safety profile of [crinecerfont] and its ability to reduce the overproduction of adrenal androgens, allowing for a meaningful reduction in glucocorticoid dosage, while maintaining or enhancing control of these androgens," CAHtalyst principal investigator Richard Auchus, MD, PhD, professor of translational medicine, professor of internal medicine, and professor of pharmacology at the University of Michigan Medical School in Ann Arbor, MI, said in the Neurocrine announcement. "Chronic treatment with supraphysiologic glucocorticoids can cause a number of short- and long-term health consequences, such as obesity, hypertension and osteoporosis, so the ability for patients with CAH to lower their glucocorticoid dose to a more physiologic level can have profound benefits."¹

Learn more in our interview with principal investigator Richard Auchus, MD, PhD, on CAHtalyst phase 3 clinical trial findings.

The enzyme deficiency that characterizes CAH, a rare genetic condition, alters the production of essential adrenal steroid hormones, eg, cortisol, aldosterone and adrenal androgens. Approximately 95% of CAH cases are caused by variants of the CYP21A2 gene that leads to deficiency of the enzyme 21-hydroxylase. Severe 21-OH deficiency leads to suppression of cortisol production and of aldosterone production in approximately three-quarters of affected individuals. Because individuals with CAH are still able to produce androgens, the unused precursors that would normally be used to make cortisol instead result in the production of excess amounts of androgens. If left untreated, CAH can result in salt wasting, dehydration and even death.¹

"Today's approval provides an important advance for patients with classic congenital adrenal hyperplasia and highlights the FDA's continued commitment to advancing effective and safe treatments for rare diseases," Theresa Kehoe MD, director of the Division of General Endocrinology in the FDA's Center for Drug Evaluation and Research. "The FDA will continue working with patients, drug companies and health care providers to address the unmet medical needs of the rare disease community."⁴

Find more details on CAH and the evolution of pharmacotherapy for the condition in the Patient Care Online CAH Provider Toolkit, including:

CAH management across the lifespan

The CRF pathway interrupted: Potential to Transform CAH Care

Monitoring glucocorticoid therapy in CAH

Treating CAH: Challenges in the transition to adult care

References

1. Neurocrine Biosciences announces FDA approval of Crenessity (crinecerfont), a first-in-class treatment for children and adults with classic congenital adrenal hyperplasia. News release. Neurocrine Biosciences. December 13, 2024. Accessed December 13, 2024. https://neurocrine.gcs-web.com/news-releases/news-release-details/neurocrine-biosciences-announces-fda-approval-crenessitytm
2. Sarafoglou K, Kim MS, Lodish M, et al. Phase 3 trial of crinecerfont in pediatric congenital adrenal hyperplasia. N Engl J Med. 2024;391:493-503. doi: 10.1056/NEJMoa2404655
3. Auchus R, Hamidi O, Pivonello R, et al. Phase 3 trial of crinecerfont in adult congenital adrenal hyperplasia. N Engl J Med. 2024;391:504-514 doi: : 10.1056/NEJMoa2404656
4. FDA approves new treatment for congenital adrenal hyperplasia. News release. FDA. December 13, 2024. Accessed December 13, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-congenital-adrenal-hyperplasia