12275 Effect Of Osilodrostat On Cardiovascular And Metabolic Manifestations Of Hypercortisolism In Patients With Non-Pituitary Cushing’s Syndrome: Findings From A Retrospective Observational Study (LINC 7)

Abstract Disclosure: N. Scheyer: Other; Self; 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. A. Mueller: Employee; Self; Recordati Rare Diseases. A. Tabarin: Consulting Fee; Self; H Lundbeck A/S, Crinetics Pharmaceuticals, HRA Pharma, Recordati Rare Diseases. Introduction: Endogenous Cushing’s syndrome (CS) is associated with increased cardiovascular morbidity and mortality because of hypercortisolism. Osilodrostat, a potent oral 11β-hydroxylase inhibitor, is approved for patients (pts) with endogenous CS (EMA) and Cushing’s disease (CD; for whom pituitary surgery is not an option or has not been curative; FDA). The long-term safety and efficacy of osilodrostat has been demonstrated in Phase II (LINC 2, NCT01331239) and Phase III (LINC 3, NCT02180217; LINC 4, NCT02697734) studies of CD pts. Here, we investigated the effect of osilodrostat on clinical manifestations of hypercortisolism in a real-world, retrospective, observational study conducted in a heterogeneous patient population with non-pituitary CS (LINC 7; NCT05633953). Methods: Adult pts with non-pituitary CS who initiated osilodrostat prior to EU approval under the French Autorisation Temporaire d’Utilisation scheme and/or, once approved, in routine clinical practice were followed up retrospectively for up to 36 months. The primary endpoint was proportion of pts with mean urinary free cortisol (mUFC) ≤upper limit of normal (ULN) at week (W) 12, based on the modified intention-to-treat (mITT) population (pts with any cortisol measurement at W12 or not collected because of safety reasons). Secondary endpoints included cardiovascular and metabolic parameters, recorded every 4 or 12W, depending on clinical practice. No formal statistical hypothesis testing was performed; all analyses are descriptive. Results: 103 pts were enrolled (mean [SD] age: 59.3 years [15.5]; female 61.2% [n=63]; adrenal adenoma [16.5%, n=17/103; mITT: 9.6%, n=5/52], adrenocortical carcinoma [18.4%, n=19/103; mITT: 11.5%, n=6/52], macronodular adrenal hyperplasia [13.6%, n=14/103; mITT: 17.3%, n=9/52], ectopic adrenocorticotropic hormone secretion [51.5%, n=53/103; mITT: 61.5%, n=32/52]). Median (min-max) osilodrostat exposure and dose at baseline was 164.0 days (1-1178) and 5.0 mg/day (1-60), respectively. Median (min-max) osilodrostat dose at W12 and W36 was 6.0 mg/day (0-60) and 10.0 mg/day (0-120), respectively. 23/52 pts (44.2%; 95% CI 30.5-58.7) had mUFC ≤ULN at W12. Mean (95% CI) changes in cardiovascular and metabolic-related parameters from baseline to W12 and W36, respectively, were: systolic blood pressure (−5.7 [−17.9, −6.6] mmHg, n=29 and −6.3 [−19.0, −6.5] mmHg, n=11); diastolic blood pressure (−4.7 [−10.6, −1.1] mmHg, n=29 and −8.2 [−20.7, −4.3] mmHg, n=11); weight (−2.3 [−4.2, −0.4] kg, n=27 and −3.6 [−9.6, −2.5] kg, n=12); body mass index (−0.8 [−1.5, −0.2] kg/m2, n=27 and −1.2 [−3.2, −0.8] kg/m2, n=12). No new safety signals were identified. Conclusions: Findings from this real-world setting show that osilodrostat provides cortisol control alongside improvements in clinical manifestations of hypercortisolism in non-pituitary CS pts, alleviating the disease burden. Presentation: 6/1/2024