Modified-release Hydrocortisone Therapy as a Treatment for CAH

Eunice Kennedy Shriver National Institute Of Child Health & Human Development

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Abstract

A 6-month, randomized, Phase 3, study in 122 adults with classic CAH, comparing a newly-developed modified-release formulation of hydrocortisone (MR-HC) with standard glucocorticoid, was completed. This newly developed formulation of hydrocortisone (Chronocort) was designed to mimic the normal cortisol circadian rhythm. In a prior Phase 2 study at the NIH, compared to conventional therapy at baseline, MR-HC at 6 months showed improved androgen levels throughout the day and this lowering of androgens was achieved with a lower or similar average daily glucocorticoid dose. This led to the 6-month randomized (MR-HC vs. standard glucocorticoid) international multi-center phase 3 clinical trial, which is the first randomized, controlled trial of glucocorticoid treatment in patients with CAH. The Phase 3 study failed its primary outcome at 6 months, which was based on 24-hour hormone profiles. However, there was evidence of better biochemical control on MR-HC between 0700h-1500h compared to standard glucocorticoid therapy, and morning hormonal control is important in controlling the overnight increase in adrenal androgens. An extension study is underway with patient-reported benefits including menses restoration and patient and partner pregnancies. This novel hydrocortisone formulation represents a potential new treatment approach for patients with CAH