Osilodrostat for the treatment of Cushing's disease

Indroduction The treatment of Cushing's disease (CD) has been advanced well with the introduction of treatment options like transsphenoidal surgery, radiosurgery, bilateral adrenalectomy, and various classes of medication; however, many patients still fail to achieve disease remission. Osilodrostat, an orally bioavailable adrenal steroidogenesis inhibitor, was approved in the USA and EU in 2020 for the treatment of CD. Areas covered This review provides an overview of Cushing's disease and the newly FDA approved 11 beta-hydroxylase inhibitor, osilodrostat, for CD with a focus on pharmacodynamics, pharmacokinetics, safety and efficacy data, and phase 2 and 3 clinical trials. Expert opinion Osilodrostat has proven clinical efficacy and tolerability in phase 2 and 3 trials with CD patients who had an inadequate or reoccurring response to transsphenoidal surgery (TSS) and conventional first-line treatment. The phase 3 trial (LINC3) had 86% of the treatment group respond with normal urinary free cortisol (UFC) level compared to 29% in the placebo group (p < 0.001). Deemed as well-tolerated in all current pivotal trials, oral osilodrostat provides a noninvasive option for patients who cannot undergo surgery or patients who have reoccurring hypercortisolemia.

Automated summary

Osilodrostat has shown clinical efficacy and tolerability in phase 2 and 3 trials with Cushing's disease patients who had inadequate response to transsphenoidal surgery (TSS) and conventional first-line treatment. In the phase 3 trial (LINC3), 86% of the treatment group achieved normal urinary free cortisol (UFC) levels compared to 29% in the placebo group (p < 0.001). Considered well-tolerated in all current pivotal trials, oral osilodrostat offers a noninvasive option for patients unable to undergo surgery or experiencing recurring hypercortisolemia.