The Food and Drug Administration (FDA) has approved Isturisa® (osilodrostat; Recordati) for the treatment of adults with Cushing disease for whom pituitary surgery is not an option or has not been curative.
Isturisa is a cortisol synthesis inhibitor that works by blocking the enzyme 11-beta-hydroxylase. The approval was based on data from the phase 3 LINC-3 study (N=137), which included a 24-week, single-arm, open-label titration and treatment period and an 8-week, double-blind, randomized withdrawal period. During the first 24 weeks, patients received osilodrostat 2mg twice daily, which could be increased every 2 weeks up to 30mg twice daily.
By the end of the 24-week period, roughly half of the patients (n=71) had cortisol levels within normal limits. These patients then entered the 8-week, double-blind withdrawal phase where they received osilodrostat or placebo. At the end of the withdrawal period, cortisol levels were maintained in 86% of osilodrostat-treated patients and 30% of placebo-treated patients.
“Until now, patients in need of medications to reduce cortisol levels have had few approved options, either with limited efficacy or with too many adverse effects,” said Maria Fleseriu, MD, FACE, professor of Medicine and Neurological Surgery and director of the Pituitary Center at Oregon Health Sciences University. “With this demonstrated effective oral treatment, we have a therapeutic option that will help address patients’ needs in this underserved patient population.”
With regard to safety, the most common adverse reactions observed were adrenal insufficiency, headache, vomiting, nausea, fatigue and edema. In addition, treatment with osilodrostat was associated with hypocortisolism, QTc prolongation, and elevations in adrenal hormone precursors and androgens.
Isturisa will be supplied as an oral tablet in 1mg, 5mg, and 10mg strengths. It is expected to be available in the second or third quarter of 2020.
For more information visit fda.gov.