Richard J. Auchus, MD, PhD, Professor of Internal Medicine and Pharmacology at the University of Michigan Medical School, discusses two-year results of Crenessity (crinecerfont) in the treatment of congenital adrenal hyperplasia (CAH).
CAH refers to a group of genetic conditions that affect the adrenal glands. Affected people lack an enzyme the adrenal glands need to make one or more of these hormones and often overproduce androgens. For example, females with a severe form of the condition may have ambiguous genitalia at birth and if not properly diagnosed, develop dehydration, poor feeding, diarrhea, vomiting and other health problems soon after. People with milder forms may not be diagnosed with the condition until adolescence or adulthood when they experience early signs of puberty or fertility problems.
At the 2026 American Association of Clinical Endocrinology (AACE) Annual Meeting, two-year data from the phase 3 CAHtalyst adult clinical trial of crinecerfont was presented. Crinecerfont is a potent and selective oral corticotropin-releasing factor type 1 receptor (CRF1) antagonist designed to reduce and control excess adrenocorticotropic hormone (ACTH) and adrenal androgens through a non-glucocorticoid (GC) mechanism.
The phase 3 CAHtalyst global registrational studies were designed to evaluate the safety, efficacy and tolerability of crinecerfont in children and adults with classic CAH due to 21-hydroxylase deficiency. The CAHtalyst Adult study included 182 adult patients ages 18 to 58 years. The study evaluated improvement of androgen control over four weeks of crinecerfont treatment and the enabling of GC reduction to physiologic range while androstenedione levels were maintained or improved over an additional 20 weeks of treatment.
At month 24 of the study, 69% (n=149) of participants achieved a physiologic GC dose, with many participants eliminating nonphysiologic GC types. Of participants originally taking dexamethasone (n=20), 75% switched to a dexamethasone-free regimen, while 62% (37/60) of patients taking more than two doses of hydrocortisone per day were able to eliminate a dose outright. GC dose reductions and regimen changes were achieved without worsening androstenedione levels relative to baseline, indicating that lowering the GC dose was not achieved at the expense of androgen control.
Long‑term treatment with crinecerfont was generally well tolerated, with more than 80% study retention at two years and no new safety signals observed.
Data from the CAHtalyst phase 3 studies supported approval of crinecerfont by the US Food and Drug Administration in December 2024. The open-label extension treatment portions of both studies are ongoing.
Chronic exposure to supraphysiologic GC doses is associated with numerous long-term health risks, including cardiometabolic, bone health and quality-of-life complications. Reducing high-dose, long-term GC exposure represents one of the most important goals in the management of classic congenital adrenal hyperplasia (CAH).
For more information, click here.
To learn more about CAH and other rare endocrine disorders, visit https://checkrare.com/diseases/endocrine-disorders/
