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Adrenal (Excluding Mineralocorticoids)

ORF05-05 - International Real-World Study on Osilodrostat Efficacy and Safety in Adrenal Cushing Syndrome.

Saturday, June 13, 2026
10:15 AM - 10:30 AM CT
Location: Room W187



Objective: To assess the effectiveness and safety of osilodrostat in ACTH independent Cushing´s syndrome (CS) and to identify if there are predictors of response to osilodrostat in patients with adrenal CS. In addition, we evaluated the impact of the treatment on the cardiometabolic profile.

Methods: International study on patients with adrenal CS: patients treated with osilodrostat at any time were enrolled in the safety evaluation and those treated for longer than 1 month, in the efficacy evaluation. Patients were classified responders if they experienced a reduction in urinary free cortisol (UFC) >50% (complete responders when UFC levels were below the upper limit of normal (ULN) and partial responders if there was a reduction of UFC >50% but not normalization).

Results: Twenty-eight patients with adrenal CS were included in the study: 16 with adrenocortical carcinoma (ACC) (13 stage IV and 3 non-metastatic ACC) and 12 with benign adrenal disease (6 with unilateral adrenal adenoma and 6 with bilateral adrenal disease). The median age of the cohort at the time of the CS diagnosis was 59.5 years (range 27-81) and 68% (n=19) were women. The median UFC (xULN) before starting osilodrostat was 4.2 (0.6-53.3). Overall, the median duration of the therapy with osilodrostat was 7 months (range 1-64). Osilodrostat was used in monotherapy in 22 patients and in combination with metyrapone in 6 cases. The median starting doses were 4 mg/day (range 1-10), the maintenance doses 9 mg/day (range 1-50) and the maximum doses 10 mg/day (range 1-50). There were 10 patients treated with osilodrostat using the B&R strategy after titration approach and one patient in the combination therapy who started B&R from the beginning.
In those patients treated for longer than 1 month (n=22), 68.2% were classified as responders (31.8% complete response and 36.4% partial response). The rate of response was 80% in the combination therapy group and 64.7% in the monotherapy group. In the group of complete responders, the median time to normalize UFC was 10 weeks (range 5-17). Response tended to be higher in patients with benign disease than with ACC (88.9% vs. 53.9%, P=0.083). The use of osilodrostat as a non-first-line therapy (Odds ratio [OR] 12.0, P=0.017) and UFC < 5xULN before osilodrostat initiation (OR 6.9, P=0.045) were predictors of response. Osilodrostat led to a significant decrease in systolic blood pressure and body weight (P < 0.05). There were 9 patients (32.1%) who developed one or more adverse events (AEs) potentially related to osilodrostat therapy and in 5 of them AEs led to osilodrostat discontinuation.

Conclusions: Osilodrostat controls hypercortisolism in 70% of patients with adrenal CS, with a positive impact on blood pressure and body weight. Patients who received osilodrostat after other previous steroidogenesis inhibitors and with UFC < 5xULN have a higher probability of response.