Modified-release Hydrocortisone Therapy as a Treatment for Adrenal Insufficiency

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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. At 18 months' extension, the percentage of patients with disease control based on serum biomarkers was 80% and daily modified-release hydrocortisone dose was on average 20 mg daily. An extension study is underway with patient-reported benefits including menses restoration and patient and partner pregnancies. Long-term findings will be key.