New Data for Osilodrostat in Cushing Syndrome

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The FDA recently expanded osilodrostat’s label to include Cushing syndrome, extending beyond its previous indication limited to Cushing disease. This expansion was based on compelling data from the LINKS-6 and LINKS-7 studies, which demonstrated long-term efficacy in normalizing urinary-free cortisol across various causes of hypercortisolism. The LINKS-6 phase 4 study results showed that patients previously treated with osilodrostat maintained normal urinary-free cortisol levels over extended periods, with particular success in those achieving normal late-night salivary cortisol levels.

The LINKS-7 retrospective European study results revealed that 44% of patients with adrenal tumors or ectopic corticotropin syndrome maintained normal mean urinary-free cortisol at 12 weeks. These studies focused on patients with elevated urinary-free cortisol as the target for normalization, representing more severe hypercortisolism than the CATALYST study population. Although diabetes improvement was noted, these patients typically entered with hemoglobin A1C levels of approximately 7% to 7.5%, indicating less severe diabetes compared with the treatment-resistant population studied in CATALYST.

Recent research has explored circadian dosing strategies for osilodrostat, recognizing that the loss of normal cortisol circadian rhythm is central to the pathophysiology of hypercortisolism. The dexamethasone suppression test specifically evaluates the ability to suppress cortisol during early morning hours, and maintaining this natural rhythm may be crucial for optimal treatment outcomes. This approach addresses the fundamental issue that cortisol’s harmful effects are most pronounced when present during periods when it should naturally be suppressed, particularly overnight.