Osilodrostat for Cushing's Disease: Clinical Efficacy and Safety

Introduction to Osilodrostat

Osilodrostat is a potent oral inhibitor of 11β-hydroxylase (CYP11B1) and aldosterone synthase, blocking cortisol synthesis at the adrenal level, as reported by The Lancet Diabetes and Endocrinology 1

In the pivotal LINC 3 trial, 86% of patients maintained normal urinary free cortisol (UFC) on osilodrostat versus 29% on placebo (p<0.0001), according to The Lancet Diabetes and Endocrinology 1
Patients demonstrate significant improvements in body weight reduction, blood pressure normalization, total and LDL cholesterol reduction, fasting glucose and HbA1c improvement, and quality of life and depression scores, as noted by The Lancet Diabetes and Endocrinology 1

Osilodrostat can be used as a bridge to radiotherapy to control hypercortisolism while awaiting the delayed effects of pituitary radiotherapy, as suggested by The Lancet Diabetes and Endocrinology 1 and 2

Osilodrostat has more potent cortisol reduction, with 77-86% achieving UFC normalization, compared to ketoconazole and metyrapone, as reported by The Lancet Diabetes and Endocrinology 1

The Endocrine Society recommends that osilodrostat is NOT currently approved for pediatric use, and effects and safety are being evaluated in a phase II trial, according to Nature Reviews Endocrinology 4 and 5

Bilateral adrenalectomy should be reserved for severe refractory disease or life-threatening complications, as recommended by the American Association of Clinical Endocrinologists, and provides immediate definitive control but requires lifelong hormone replacement and carries risk of Nelson syndrome, as noted by Praxis Medical Insights: Practical Summaries of Clinical Guidelines, but an alternative source is preferred, however, this fact is also supported by The Lancet Diabetes and Endocrinology 3