A Cushing’s disease drug whose rights Novartis sold to Italy-based Recordati last year now has FDA approval.
Cushing’s disease is a rare disorder in which the adrenal glands make too much of a hormone called cortisol. The Novartis (NYSE: NVS) drug, osilodrostat (Isturisa), is intended to block an enzyme key to cortisol production. The FDA says its approval of osilodrostat is the first for a drug that works in this manner.
Weight gain is an early sign of Cushing’s disease. Patients can go on to develop high blood pressure, type 2 diabetes, brittle bones that are prone to fracture, and a weakened immune system that raises the risk of infections. Though Cushing’s disease is a hormonal problem, it stems from a tumor on the pituitary gland, the FDA says. This tumor releases too much of a hormone called adrenocorticotropin, which in turn drives up cortisol production. The disease affects an estimated 10 million to 15 million people worldwide and, for reasons that are unclear, affects women more than men, according to the National Institutes of Health.
The Novartis drug was designed to block 11-beta-hydroxylase, an enzyme that helps the adrenal glands produce cortisol. The FDA’s approval of the drug covers adults who can’t undergo surgery to their pituitary glands, or those who have undergone surgery but still have the disease.
That’s a different approach than another Cushing’s disease drug from Novartis, pasireotide, which was approved by the FDA in 2014. That injectable drug is an analog to somatostatin, a hormone produced by the body that blocks the production and release of adrenocorticotropin. Novartis sold both osilodrostat and pasireotide last summer to Milan, Italy-based Recordati in a $390 million deal.
The FDA’s approval of osilodrostat, a twice-daily pill, is based on an open-label study that tested the drug in 137 adults. Most of those patients had undergone surgery that did not cure their disease or were not candidates for surgery. After 24 weeks, about half of the patients had cortisol levels within a normal range. At that point, 71 patients were entered into an eight-week withdrawal study in which they were randomly assigned to receive either osilodrostat or a placebo. At the end of the withdrawal period, the FDA says 86 percent of patients who received the Novartis drug maintained normal cortisol levels compared to 30 percent of those who were given a placebo.
The most common side effects reported in the study were adrenal insufficiency, in which the adrenal glands do not produce enough steroid hormones; headache, vomiting, nausea, fatigue, and swelling. Other problems that can occur include low cortisol levels, and a heart rhythm condition called prolonged QTc.
Recordati sells drugs for cardiovascular, urological, and rare disorders. In 2018, private equity firm CVC Capital Partners acquired a majority stake in Recordati via a deal that valued the drug maker at about $6.8 billion, according to Pitchbook.