General Information

Isturisa (osilodrostat) is a cortisol synthesis inhibitor .

Isturisa is specifically indicated for the treatment of patients with Cushing’s disease for whom pituitary surgery is not an option or has not been curative.

Isturisa is supplied as a tablet for oral administration. Correct hypokalemia and hypomagnesemia prior to starting Isturia. Obtain baseline electrocardiogram (ECG). Repeat ECG within one week after treatment initiation, and as clinically indicated thereafter.

Initiate dosing at 2 mg orally twice daily, with or without food. Initially, titrate the dosage by 1 to 2 mg twice daily, no more frequently than every 2 weeks based on the rate of cortisol changes, individual tolerability and improvement in signs and symptoms of Cushing’s disease. If a patient tolerates Isturisa dosage of 10 mg twice daily and continues to have elevated 24-hour urine free cortisol (UFC) levels above upper normal limit, the dosage can be titrated further by 5 mg twice daily every 2 weeks. Monitor cortisol levels from at least two 24-hour urine free cortisol collections every 1-2 weeks until adequate clinical response is maintained.The maintenance dosage of Isturisa is individualized and determined by titration based on cortisol levels and patient’s signs and symptoms. The maintenance dosage varied between 2 mg and 7 mg twice daily in clinical trials. The maximum recommended maintenance dosage of Isturisa is 30 mg twice daily. Once the maintenance dosage is achieved, monitor cortisol levels at least every 1-2 months or as indicated.

Clinical Trials

The FDA approval of Isturisa was the Phase III LINC-3 clinical trial, which enrolled 137 adults, about 75% of who were women, with a mean age of 41 years. The majority either had pituitary surgery that didn’t cure the disease or who were not candidates for the surgery. In the 24-week, single-arm, open-label period, all patients received a starting dose of 2 milligrams of Isturisa twice a day that could be increased every two weeks up to 30 mg twice a day. At the end of the 24-week period, approximately half of patients had normal cortisol levels. At that time, 71 patients who did not need dose increases and tolerated the drug for at least 12 weeks joined an eight-week, double-blind, randomized withdrawal trial where they were given either Isturisa or a placebo. At the end of this withdrawal period, 86% of patients receiving the drug maintained cortisol levels with normal limits compared to 30% of placebo patients.