The FDA has approved Novartis AG’s Isturisa (osilodrostat), an oral treatment for adults with Cushing’s disease, a rare condition of the adrenal glands. It’s the first FDA-approved 11‐beta‐hyrdoxylase inhibitor that addresses cortisol overproduction and synthesis.

On Oct. 23, Milan’s Recordati SpA acquired worldwide rights to osilodrostat from Novartis, which received $390 million in the deal. Recordati owes milestone payments for the approval and market access of osilodrostat as well as royalties on sales of the drug. The FDA decision confirmed the orphan status of Isturisa, providing seven years of market exclusivity, Recordati officials said. 

Recordati expects Isturisa to become commercially available in the U.S. in the second or third quarter of 2020.

Osilodrostat is a steroidogenesis inhibitor working much like Metopirone (metyrapone, Laboratoire HRA Pharma), used off-label as a steroidogenesis inhibitor, but it appears to be a more potent inhibitor of 11-beta hydroxylase. In a phase III study, 86% of patients achieved normal mean urinary free cortisol at week 34, compared to 29% for placebo (p<0.001). By week 48, 66% of patients had achieved normal mean urinary free cortisol. The most common side effects reported in the clinical trial for Isturisa were adrenal insufficiency, headache, vomiting, nausea, fatigue and edema.

Cushing’s disease is an endocrine disease caused by a pituitary adenoma, a gland enlargement leading to cortisol overproduction. Once properly diagnosed by an endocrinologist, about 70% of patients can have surgery to remove the benign adenomas that stimulate the adrenal gland to make cortisol. But because the tumors are small, they often aren't fully removed, and about 50% of patients have recurrence of the disease.

Isturisa, for Cushing’s patients for whom pituitary surgery is not an option or has not been curative, was granted marketing authorization by the European Commission in January. It was designated an orphan medicine by the EMA in 2014.

Isturisa is taken by mouth twice a day, in the morning and evening.

Amidst a global market self-off, Recordati’s stock (REC.MI) sagged 5.6% this morning. Recordati Rare Diseases Inc. is part of the rare diseases business within the Recordati Group, which launched a U.S. endocrinology business unit.