LBMON176 Management, Safety, And Efficacy Of Osilodrostat Treatment In US Patients With Non-pituitary Cushing's Syndrome: Results From The ILLUSTRATE Study

Abstract Background Osilodrostat, a potent cortisol synthesis inhibitor, demonstrated safety and efficacy in the treatment of Cushing's disease (CD). No information is available describing use of osilodrostat in non-pituitary Cushing's syndrome (CS) in US patients. Data from a real-world study in US patients with non-pituitary CS is presented. Methods The ILLUSTRATE study is a real-world characterization of osilodrostat usage in patients with endogenous CS treated May 1, 2020 - October 29, 2021. Forty-two adult patients with a confirmed diagnosis of endogenous CS and a prescription for osilodrostat were included in this real-world study. We report patient characteristics, osilodrostat dose, efficacy, and safety in the subset of patients with non-pituitary CS (n=8,19%). Results The 8 non-pituitary CS patients enrolled comprised 5 with adrenal CS and 3 with ectopic CS. Baseline urinary free cortisol (UFC) was 2.57–75.2×ULN in patients with ectopic CS, and 0.42–27.76×ULN in the 4 adrenal patients with baseline UFC available. In the adrenal CS patients, starting dose ranged from 1–4 mg daily. In adrenal patients with more than one documented clinical encounter (n=4): 2 remained on starting doses of 1 mg BID and 2 mg BID, 1 increased from 1 mg QD to 2 mg BID on day (D) 50, and 1 increased from 2 mg BID to 4 mg BID on D5 and required down-titration on D18 with treatment interruption on D27. The 3 patients with ectopic CS were all initiated at 2 mg BID: 1 patient's dose was unchanged throughout the observation period, and the other 2 patients were up-titrated, both on D91 to 4 mg BID or 5 mg QD. The two ectopic CS patients with available UFC data experienced substantial UFC | reductions (from 57.1×ULN to 2.9×ULN at D91 and 75.2×ULN to 0. 076×ULN at D134). The one adrenal CS patient with available UFC data and prior medical therapy for CS maintained UFC ≤ ULN during osilodrostat treatment. Osilodrostat was generally well tolerated and one ectopic CS patient had treatment interrupted on D214 for adrenal insufficiency (AI). Two of five adrenal CS patients (40%) had symptoms suggestive of glucocorticoid withdrawal (e. g., fatigue, nausea, and headache) and one had an interruption in therapy. Neither had documented AI. Conclusion In this real-world cohort of patients treated with osilodrostat for non-pituitary CS, large UFC reductions were seen in two patients with ectopic CS. All 8 were initiated on ≤2 mg BID, with 3 (38%) remaining on their original dose. In the majority of those up-titrated, there was an extended titration interval. The observed safety profile in this subset (albeit small) of non-pituitary CS patients was consistent with the known osilodrostat safety profile. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.