SAT-671 Safety And Effectiveness Of Osilodrostat In Patients With Non-Pituitary Cushing’s Syndrome: Results From The Retrospective Observational LINC 7 Study

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Abstract A. Tabarin: Consulting Fee; Self; H Lundbeck A/S, Crinetics Pharmaceuticals, HRA Pharma, Recordati Rare Diseases. J. Bertherat: Consulting Fee; Self; Novartis, HRA Pharma, Recordati Rare Diseases. B. Decoudier: Consulting Fee; Self; Recordati Rare Diseases. H. Lasolle: Speaker; Self; Recordati Rare Diseases. H. Lefebvre: Speaker; Self; Recordati Rare Diseases. D. Drui: None. C. Vaillant: None. J. Morera: None. F. Castinetti: Consulting Fee; Self; HRA Pharma Rare Diseases, Recordati Rare Diseases. Grant Recipient; Self; HRA Pharma Rare Diseases, Recordati Rare Diseases. J. Cristante: Grant Recipient; Self; HRA Pharma, Pfizer, Inc.. N. Chevalier: None. S. Fodil-Cherif: None. A. Antonellini: Employee; Self; Recordati Rare Diseases. W. Agbotounou: Employee; Self; Recordati Rare Diseases. M. Maldonado: Employee; Self; Recordati Rare Diseases. N. Scheyer: Other; Self; Recordati Rare Diseases. Introduction: Endogenous Cushing’s syndrome (CS) is a rare disorder of cortisol excess. Cushing’s disease (CD) is the most common form of CS. Osilodrostat, a potent oral 11β-hydroxylase inhibitor, was an effective long-term therapy for CD patients (pts) in pivotal Phase II (LINC 2, NCT01331239) and III (LINC 3, NCT02180217; LINC 4, NCT02697734) trials. Osilodrostat is approved for pts with endogenous CS (EMA) and CD (FDA; for whom pituitary surgery is not an option or has not been curative). Given the heterogeneity of non-pituitary CS pts, LINC 7 (NCT05633953) was a retrospective, non-interventional study conducted to evaluate the safety and effectiveness of osilodrostat in these pts, in a real-world setting. Methods: Non-pituitary CS pts who initiated osilodrostat under the French Autorisation Temporaire d’Utilisation scheme and/or, once approved, in routine clinical practice were followed retrospectively for up to 36 months. The primary endpoint was the proportion of pts with mean urinary free cortisol (mUFC) ≤upper limit of normal (ULN) at week (W) 12. Secondary and exploratory endpoints included proportion of pts with any cortisol normalization (mUFC, late-night salivary cortisol, morning serum cortisol) at certain timepoints, mUFC and any cortisol ≤ULN at last on-treatment assessment, and adverse event (AE) occurrence. Safety data are reported for all pts. There was no formal statistical hypothesis testing; all analyses are descriptive. Results: 103 pts were enrolled: ectopic adrenocorticotropic hormone secretion (EAS; 51.5% [n=53]), macronodular adrenal hyperplasia (13.6% [n=14]), adrenocortical carcinoma (ACC; 18.4% [n=19]), adrenal adenoma (16.5%, [n=17]). Median (min-max) osilodrostat exposure and dose at baseline (BL) was 164 days (1-1178) and 5.0 mg/day (1-60). Mean (SD) BL mUFC was 1518.6 (3679.8) µg/24h. 52 pts were included in the modified intention-to-treat population; 23/52 (44.2%; 95% CI 30.5, 58.7) had mUFC ≤ULN at W12 and 9/18 (50.0%; 95% CI 26.0, 74.0) at W24. At W12, 28/46 (60.9%; 95% CI 45.4, 74.9) pts had any cortisol ≤ULN. At last on-treatment assessment, 33/58 (56.9%; 95% CI 43.2, 69.8) pts had mUFC ≤ULN and 52/75 (69.3%; 95% CI 57.6, 79.5) had any cortisol ≤ULN. Most common (≥15%) treatment-emergent AEs were adrenal insufficiency (28.2%, n=29) and hypokalemia (17.5%, n=18). Hypocortisolism-related AEs occurred in 30.1% of pts. 29 pts (EAS, n=24; ACC, n=5) died during the study. 35 (34.0%) pts discontinued because of investigator-reported AEs, 11 because of neoplasm progression. 15 pts discontinued because of planned surgery for CS. Conclusions: Data from this retrospective real-world study show that osilodrostat provides sustained cortisol control in non-pituitary CS pts with a safety profile consistent with the known safety profile of osilodrostat and the morbidity of the study population. Saturday, June 1, 2024

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