FDA Approves Osilodrostat, A Non-Surgical Option for Cushing's Disease

In a move that is sure to receive applause from the rare disease community, the US Food and Drug Administration (FDA) has announced the approval of osilodrostat (Isturisa) oral tablets for the treatment of Cushing’s disease in patients who cannot undergo surgery or still have the disease despite surgery.

The treatment, which is produced by Novartis, is the first FDA-approved drug to directly address this cortisol overproduction by blocking the 11-beta-hydroxylase and preventing cortisol synthesis, according to a statement from the FDA.

"The FDA supports the development of safe and effective treatments for rare diseases, and this new therapy can help people with Cushing's disease, a rare condition where excessive cortisol production puts them at risk for other medical issues," said Mary Thanh Hai, MD, acting director of the Office of Drug Evaluation II in the FDA's Center for Drug Evaluation and Research, in the aforementioned statement. "By helping patients achieve normal cortisol levels, this medication is an important treatment option for adults with Cushing's disease."

The approval of osilodrostat oral tablets was supported by a clinical trial that evaluated the treatment’s safety and efficacy for treating Cushing’s disease in 137 adult patients. According to the FDA, most study participants had either undergone pituitary surgery or were not surgical candidates. During the study’s 24-week, single-arm, open-label period, patients received a starting dose of osilodrostat 2 mg twice a day that could be increased every two weeks up to 30 mg twice a day. At the end of this period, approximately half of the study participants had normal cortisol levels.

From here, 71 patients—who did not need further increases—were enrolled in an 8-week, double-blind withdrawal study and randomized to either osilodrostat or placebo therapy. At the conclusion of the 8-week period, 86% of osilodrostat patients maintained cortisol levels within normal limits compared to 30% of the placebo group, according to the FDA.

Common side effects reported in the aforementioned trial included adrenal insufficiency, headache, vomiting, nausea, fatigue, and edema. Prescribing information notes that hypocortisolism, QTC prolongation, and elevations in adrenal hormone precursors may also occur in patients taking osilodrostat.