Osilodrostat oral tablets for adults with Cushing's disease. Issue 2 (4th March 2022)

• Record Type: Journal Article
• Authors: Martino, Marianna; Aboud, Nairus; Lucchetti, Beatrice; Salvio, Gianmaria; Arnaldi, Giorgio
• Is Part Of: Expert review of endocrinology & metabolism. Volume 17:Issue 2(2022)
• Page Start: 99
• Page End: 109
• Publication Date: 2022-03-04
• Subjects: Steroidogenesis inhibitor -- hypercortisolism -- glucocorticoid excess -- medical therapy; Endocrinology -- Periodicals; Metabolism -- Periodicals; 616.4
• DOI: 10.1080/17446651.2022.2044789
• Languages: English
• ISSNs: 1744-6651

Abstract

ABSTRACT: Introduction: Endogenous Cushing's syndrome (CS) is a rare, multi-systemic condition resulting from chronic glucocorticoid excess sustained by a pituitary adenoma (Cushing's disease, CD), an adrenal adenoma or, less frequently, a neuroendocrine tumor. The optimal first-line option is surgery, but when it is contraindicated/refused, or in case of severe, life-threatening disease, medical treatment is a first-line choice. Osilodrostat (LCI699, Isturisa®) is a new, orally active adrenal steroidogenesis inhibitor currently approved by the FDA and EMA for the treatment of endogenous CS Areas covered: We illustrate the pharmacologic profile of osilodrostat and summarize the efficacy and safety of osilodrostat from the first phase I studies to the most recent evidence. Expert opinion: Osilodrostat acts as a potent, reversible inhibitor of 11β-hydroxylase (CYP11B1) and 18-hydroxylase (or aldosterone synthase, CYP11B2), counteracting both gluco- and mineralocorticoid production. According to the results of the LINC1, LINC2, and LINC3 studies and the preliminary findings of LINC4, osilodrostat offers an excellent efficacy in controlling hypercortisolism with a good tolerability. The non-negligible risk of adrenal insufficiency/steroid withdrawal symptoms, hypokalemia, and hyperandrogenism disorders, and the possibility, albeit rare, of pituitary tumor enlargement, require further confirmation and careful monitoring.