Key Takeaways
- Crenessity supports steroid dose reduction: Patients achieved up to a 30% reduction in glucocorticoid use while maintaining hormone control.
- Sustained hormonal balance over one year: Adrenocorticotropic hormone, 17-hydroxyprogesterone, and androstenedione levels remained at or below baseline throughout treatment.
- Improved metabolic and clinical outcomes: Crenessity led to lower insulin resistance and reduced hirsutism in female patients.
Results from the Phase III CAHtalyst trial show that Neurocrine Biosciences’ Crenessity (crinecerfont) demonstrated sustained efficacy in adults with classic congenital adrenal hyperplasia (CAH). According to the company, results also indicated that patients treated with Crenessity achieved and maintained lower, more physiologic glucocorticoid (GC) doses while keeping key adrenal biomarkers—adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), and androstenedione (A4)—at or below baseline levels.1
How Did Crenessity Perform Over One Year in Adults with Classic CAH?
"Results from the pivotal CAHtalyst clinical trial program continue to reinforce the critical role of Crenessity in the management of classic congenital adrenal hyperplasia," said Sanjay Keswani, MD, chief medical officer, Neurocrine Biosciences, in a press release.
Trial Design and Endpoints
- The randomized, double-blind, placebo-controlled CAHtalyst trial evaluated the safety and efficacy of Crenessity in 182 patients with CAH due to 21-hydroxylase deficiency.
- The primary endpoint of the study was the percent change from baseline in glucocorticoid daily dose at week 24.
- Secondary outcomes included but were not limited to change from baseline in serum androstenedione at week four, the number of patients who achieved a reduction to physiological glucocorticoid dose while maintaining androstenedione control at week 24, change from baseline in homeostatic model assessment of insulin resistance (HOMA-IR) at week 24, and the percent change from baseline in body weight at week 24.2
Key Efficacy Results
- Results showed that patients administered continuous doses of Crenessity experienced 25% reductions in GC doses, while those in the placebo to Crenessity group experienced a 30% reduction while maintaining or improving A4 levels.
- The proportion of patients achieving physiologic GC dosing, defined in the study as 11 mg/m²/day or less in hydrocortisone equivalents, while maintaining hormonal control remained stable between six and 12 months.
- Both 17-OHP and ACTH levels were sustained or lowered below baseline.
- The average insulin resistance score based on HOMA-IR started at 3.2 for those on continuous Crenessity and 3.1 in patients who initially received a placebo. After one year of treatment, insulin resistance decreased by 0.5 points in the continuous treatment group and by 0.9 points in the transition group.
- In female patients, the average hirsutism score was 40.6 in the Crenessity group and 37.4 in the placebo group. By the end of the year, scores dropped by 11.5 points in those continuously taking Crenessity and by 12.9 points in those who switched from placebo.
Safety Profile of Crenessity
- The safety profile of Crenessity was found to be consistent and well-tolerated.
- The most common adverse events (AEs) in patients treated with Crenessity included headache and fatigue. Both were more common during the double-blind, placebo-controlled compared to the open-label period.
- Other common AEs included dizziness, joint pain, back pain, decreased appetite, and muscle pain.
- Most AEs were reported to be mild to moderate in severity, with low rates of dicontinuations.1
CAH Prevalence and Context
According to a study published by the National Center for Biotechnology Information, the global incidence of classic CAH is approximately one in every 15,000 to 20,000 births in Western countries. In the United States, it is more common in Native American and Yupik populations. Among Caucasians, the prevalence is about one in 15,000. Non-classic CAH has a global prevalence of one in 1,000, though it may be as high as one in 100 or 200 depending on the ethnic group.3
"These one-year data show the lasting ability of Crenessity to effectively manage the ACTH and adrenal steroid imbalances in adults while allowing for lower, more physiologic steroid dosing and improved clinical outcomes,” continued Keswani, in the press release.
References
- Neurocrine Biosciences Presents One-Year Data Showing Sustained Efficacy of CRENESSITY® (crinecerfont) in Adult Patients, at ENDO 2025. PR Newswire. July 14, 2025. Accessed July 14, 2025. https://prnmedia.prnewswire.com/news-releases/neurocrine-biosciences-presents-one-year-data-showing-sustained-efficacy-of-crenessity-crinecerfont-in-adult-patients-at-endo-2025-302503650.html
- Global Safety and Efficacy Registration Study of Crinecerfont for Congenital Adrenal Hyperplasia (CAHtalyst). Clinicaltrials.gov. Accessed July 14, 2025. https://clinicaltrials.gov/study/NCT04490915?term=CAHtalyst&rank=1
- Congenital Adrenal Hyperplasia. NIH. Accessed July 14, 2025. https://www.ncbi.nlm.nih.gov/books/NBK448098/#:~:text=The%20global%20incidence%20of%20classic,have%20the%20simple%20virilizing%20form.
