OBJECTIVES: Cushing's Disease (CD) is a rare, chronic condition that results in high morbidity, caused by prolonged elevation of circulating free cortisol levels. Osilodrostat, a newly approved steroidogenesis inhibitor has been shown to achieve fast and high rates of cortisol normalisation. This research evaluates the relative time to complete response (CR) of osilodrostat compared with pasireotide subcutaneous (SC) and long-acting release (LAR) for patients with CD.

METHODS: Osilodrostat and pasireotide were investigated in prospective clinical trials in the treatment of patients with CD. Patient-level data were available for one osilodrostat trial (LINC-3), one pasireotide SC trial (PASSPORT) and one pasireotide LAR trial (CSOM230G2304). A propensity score weighted analysis was performed to adjust the pasireotide trial populations to be similar to the LINC-3 population in terms of the selected baseline characteristics (age, race, mean urinary free cortisol [mUFC], time since diagnosis, prior surgery and prior medications). The patient-level data and derived propensity score weights were used to conduct an unanchored indirect treatment comparison of osilodrostat versus pasireotide SC, and osilodrostat versus pasireotide LAR for the outcome of time to CR, mUFC ≤ 1.0 x the upper limit of normal.

RESULTS: Treatment with osilodrostat was associated with significantly reduced time to CR compared with pasireotide SC (hazard ratio [HR]: 9.15 [95% confidence interval [CI]: 4.33, 19.35]) and pasireotide LAR (HR: 4.72 [95% CI: 2.41, 9.25]). Kaplan–Meier curves suggest 99.0% of osilodrostat patients in the LINC-3 population will achieve CR within 6 months compared with 32.0% of pasireotide SC and 68.3% of pasireotide LAR patients. Sensitivity analyses investigating different stopping and censoring rules provided consistent results.

CONCLUSIONS: Osilodrostat significantly reduces the time to CR compared with pasireotide SC and pasireotide LAR suggesting that osilodrostat is an efficacious treatment option to rapidly reduce cortisol levels in patients with CD.