FDA approves oral treatment for Cushing’s disease
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The FDA has approved the nonsteroidal corticosteroid biosynthesis inhibitor osilodrostat for adults with Cushing’s disease who cannot undergo pituitary gland surgery or have undergone the surgery but still have the disease, according to an agency press release.
Osilodrostat (Isturisa, Novartis), an oral therapy originally developed for hypertension management, is the first FDA-approved drug to directly inhibit 11-beta-hydroxylase, preventing cortisol synthesis, according to 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,” Mary Thanh Hai, MD, acting director of the Office of Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research, said in the release. “By helping patients achieve normal cortisol levels, this medication is an important treatment option for adults with Cushing’s disease.”
The therapy joins two other FDA-approved treatments for Cushing’s disease . In June 2018, the FDA approved pasireotide (Signifor, Novartis) for the treatment of people with Cushing’s disease for whom pituitary surgery is not an option or has not been curative. In 2012, the FDA approved mifepristone (Korlym, Corcept Therapeutics) as a once-daily oral medication to treat adults with Cushing’s syndrome who had elevated blood glucose due to type 2 diabetes.
Researchers evaluated the safety and effectiveness of osilodrostat in a study of 137 adults with Cushing’s disease (mean age, 41 years). Most patients had undergone pituitary surgery that was not curative or were not surgical candidates. During a 24-week, single-arm, open-label period, all participants received a starting dose of 2 mg osilodrostat twice daily, titrated every 2 weeks up to 30 mg twice daily. At 24 weeks, about half of participants had cortisol levels within normal limits, with 71 participants who did not need further dose increases entering an 8-week, double-blind, randomized withdrawal study in which they received osilodrostat or placebo. At the end of the withdrawal period, 86% of participants assigned osilodrostat maintained cortisol levels within normal limits compared with 30% of those assigned placebo.
The FDA noted that the most common adverse effects reported during the clinical trial were adrenal insufficiency, headache, vomiting, nausea, fatigue and edema. Hypocortisolism, QTc prolongation and elevations in adrenal hormone precursors and androgens may also occur in people taking osilodrostat.
The FDA granted osilodrostat orphan drug designation, a special status granted to a drug intended to treat a rare disease or condition. – by Regina Schaffer
Disclosure: Hai is acting director of the Office of Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research.