Osilodrostat oral tablets for adults with Cushing's disease.

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.

• Authors: Marianna Martino, Nairus Aboud, Beatrice Lucchetti, Gianmaria Salvio, Giorgio Arnaldi
• Journal: Expert review of endocrinology & metabolism (Expert Rev Endocrinol Metab) Vol. 17 Issue 2 Pg. 99-109 (03 2022) ISSN: 1744-8417 [Electronic] England
• PMID: 35220871 (Publication Type: Journal Article)

Chemical References

• Imidazoles
• Pyridines
• Tablets
• Osilodrostat
• Mixed Function Oxygenases

Topics

• Adult
• Cushing Syndrome (drug therapy)
• Humans
• Imidazoles (therapeutic use)
• Mixed Function Oxygenases (therapeutic use)
• Pituitary ACTH Hypersecretion (drug therapy)
• Pituitary Neoplasms (drug therapy)
• Pyridines
• Tablets (therapeutic use)