New Treatment for Adults with Cushing's Disease Receives FDA Approval

The FDA also granted osilodrostat orphan drug designation.

The FDA has approved osilodrostat (Isturisa, Novartis) oral tablets for adults with Cushing’s disease who either cannot undergo pituitary gland surgery or have undergone surgery but still have the disease. The FDA also granted osilodrostat orphan drug designation.

Cushing’s disease is caused by a pituitary tumor that releases too much adrenocorticotropin, stimulating the adrenal gland to over-produce cortisol. The disease is most common among adults between 30 and 50 years old and it affects women 3 times more often than men. It can cause significant health issues, including high blood pressure, obesity, type 2 diabetes, blood clots in the legs and lungs, bone loss and fractures, a weakened immune system, and depression.

“By helping patients achieve normal cortisol levels, this medication is an important treatment option for adults with Cushing’s disease,” said Mary Thanh Hai, MD, acting director of the Office of Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research.

The drug is taken orally twice per day as directed by a health care provider. After treatment has started, dosages may be reevaluated depending on the patient’s response.

Osilodrostat was evaluated in a study of 137 adult patients with a mean age of 41 years. Most of the patients had either undergone pituitary surgery that did not cure the disease or were not surgical candidates.

In the 24-week, single-arm, open-label period, all patients received a starting dose of 2 mg of osilodrostat twice per day. The dosage could be increased every 2 weeks up to 30 mg twice daily. At the end of this period, approximately half of patients had cortisol levels within normal limits.

Following the first period, 71 patients who did not need further dose increases and tolerated the drug for the last 12 weeks entered an 8-week, double-blind, randomized withdrawal study in which they either received osilodrostat or a placebo. At the end of the withdrawal period, 86% of patients receiving osilodrostat maintained normal cortisol levels compared with 30% of patients receiving the placebo.

The most common adverse effects reported in the trial included adrenal insufficiency, headache, vomiting, nausea, fatigue, and edema. Hypocortisolism, QTc prolongation, and elevations in adrenal hormone precursors and androgens are also possible in patients receiving osilodrostat.

REFERENCE

FDA Approves New Treatment for Adults with Cushing’s Disease [news release]. White Oak, MD; March 6, 2020. FDA website, https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-adults-cushings-disease. Accessed March 9, 2020.