Real-world osilodrostat effectiveness and safety in non-pituitary Cushing syndrome

Context Osilodrostat’s clinical development program mostly enrolled Cushing disease patients. Data in non-pituitary Cushing syndrome (CS) are limited. Objective Evaluate osilodrostat effectiveness and safety in non-pituitary CS in real-world practice in France. Design Retrospective, observational study (LINC 7; NCT05633953). Data for patients who initiated osilodrostat under the French Autorisation Temporaire d’Utilisation scheme or, once approved, in routine clinical practice were extracted retrospectively for ≤36 months (2019–2022). Setting Multicenter institutional practice. Patients or Other Participants 103 adult non-pituitary CS patients: ectopic adrenocorticotropic hormone secretion (EAS), n=53; adrenocortical carcinoma (ACC), n=19; adrenal adenoma (AA), n=17; bilateral adrenal nodular disease (BND), n=14. 43 remained on osilodrostat throughout the observation period. Intervention Median (min–max) osilodrostat exposure and baseline dose: 177 days (1–1178), 5.0 mg/day (1–60). Main Outcome Measure Proportion with mean urinary free cortisol (mUFC) ≤ upper limit of normal (ULN) at week (W) 12 (modified intention-to-treat [mITT] population: all enrolled patients with ≥12W follow-up, excluding patients without W12 mUFC for non-safety reasons). Results Osilodrostat was initiated and titrated based on investigator judgment. Cortisol decreased by W4, remaining stable thereafter. 23/52 patients (mITT; 44.2%, 95% CI 30.5–58.7) had mUFC ≤ULN at W12 (missing values input as non-responders). 45/52 had W12 mUFC available; proportion with mUFC ≤ULN by etiology: EAS, n=12/29 (41%); ACC, n=4/6; AA, n=1/3; BND, n=6/7. Most common (≥15%) TEAEs: adrenal insufficiency (28%) and hypokalemia (18%). 29 patients (EAS, n=24; ACC, n=5) died from AEs (n=1 assessed as osilodrostat related by investigator), mostly neoplasm progression (n=11). Conclusions Osilodrostat is a suitable treatment for endogenous Cushing syndrome of various non-pituitary etiologies.