FDA approves ex-Novartis drug for Cushing’s disease
Two months after winning European approval, a one-time Novartis orphan drug for Cushing’s disease has been OK’d by the FDA.
Isturisa, known chemically as osilodrostat, has been approved as a twice-daily pill for those who have not undergone the pituitary gland surgery often used to treat Cushing’s disease, or for those whose symptoms persist after the operation. Novartis sold the compound alongside two other endocrine drugs to the Italian pharma Recordati last July for $390 million, plus Isturisa milestones.
A moderate deal relative to Novartis’s often high-rolling table, the terms reflected the real but limited market potential for that slice of the company’s endocrine portfolio. Generally caused by a non-cancerous tumor on the pituitary gland that causes the body to release too much cortisol, Cushing’s affects a little over a million Americans each year. It can cause a range of health problems, including high blood pressure, type 2 diabetes and change in appearance. In addition to Isturisa, the deal also included already approved Cushing’s disease drugs Signifor and Signifor LAR.
Most patients are treated with surgery, but not all patients are eligible for surgery, and surgery doesn’t always work. For those patients, doctors often prescribe drugs that block human growth hormone, such as Signifor, or a drug that blocks an enzyme involved in cortisol production, such as metyrapone.
Isturisa works by targeting a new enzyme. It blocks 11-beta-hydroxylase, one of the last enzymes in a chain the body uses to make cortisol.
In a Phase III trial of 137 adults last year, the drug brought about half of all patients down to normal cortisol production during the 24-week, single-arm, open-label phase. The 71 patients who tolerated and responded to the drug were then enrolled in an 8-week double-blind phase, testing it against placebo. At the end of the phase, 86% on the drug arm had cortisol within normal ranges, compared with 30% of placebo patients.
Still, the limited trial left key questions unanswered, most notably how long it will work. After the Endocrine Society meeting where the trial results were announced, session co-moderator and associate director of the Pituitary Center at the University of Pennsylvania Julia Kharlip told Medscape, “It is likely going to work.”
But she cautioned that the drug it replaces — metyrapone, which is taken four times a day and blocks a different enzyme — is known to eventually become ineffective as the tumor essentially overrides the enzyme blockade.