OSILODROSTAT IS EFFECTIVE AND WELL- TOLERATED IN ASIAN AND NON-ASIAN PATIENTS WITH CUSHING’S DISEASE: RESULTS FROM LINC 3 (PHASE III STUDY)

Abstract

OBJECTIVES
Osilodrostat, a potent oral 11β-hydroxylase inhibitor, normalised mean urinary free cortisol (mUFC) in most patients with Cushing’s disease (CD) during a Phase III study (LINC 3; NCT02180217). We describe outcomes for Asian and non-Asian patients enrolled in LINC 3.

METHODOLOGY
CD patients with mUFC>1.5x upper limit of normal (ULN) received osilodrostat during the 48-week (W) core phase. Patients benefiting from osilodrostat at W48 could enter an optional extension. Dose adjustments were permitted (maximum dose 30 mg bid). Data are reported separately for Asian and non-Asian patients.

RESULTS
Twenty eight percent of patients were Asian (39/137) and enrolled in Korea (n = 14), Japan (n = 9), India (n = 7), Thailand (n = 5) and China (n = 4). Most non-Asian patients were Caucasian (n = 89/98;91%). Median (range) osilodrostat exposure from baseline to study end was 115 (1–194) weeks in Asian patients and 141 (4–245) weeks in non-Asian patients, median (range) osilodrostat dose was 3.7 (1–18) and 10.1 (1–47) mg/day, respectively. The mUFC was ≤ULN in 62% (24/39) of Asian and 68% (67/98) of non-Asian patients at W48, increasing to 68% (21/31) and 87% (65/75), respectively, at W72. Improvements in cardiovascular parameters were observed in both groups during osilodrostat treatment. Hypocortisolism-related adverse events, mostly of mild or moderate severity, occurred in 64% (25/39; n = 2 discontinued) of Asian and 50% (49/98; n = 3 discontinued) of non-Asian patients.

CONCLUSION
Beneficial effects of osilodrostat were similar in Asian and non-Asian patients in terms of biochemical control and clinical improvement, although Asian patients generally received lower doses. Osilodrostat was well tolerated in both groups.