Mifepristone has been approved for the treatment of the orphan disease Cushing’s syndrome, without a risk evaluation and mitigation strategy, despite the drug’s other use as an abortifacient, according to a statement by the Food and Drug Administration.

The FDA announced approval of the mifepristone formulation, to be marketed as Korlym, to control high blood sugar levels in adults with endogenous Cushing’s syndrome on Feb. 17. It is the first approval for Corcept Therapeutics Inc. and the first therapy available for the condition.

Corcept announced in December that the FDA would not require a risk evaluation and mitigation strategy (REMS) for the drug, also known as RU-486 and used for terminating pregnancy. Several factors figured into determining that Korlym would not require a REMS, the FDA explained in a release announcing the approval. Currently, there are no approved therapies for this debilitating form of Cushing’s, and a REMS might prove an impediment to treatment; the number of patients is small; the number of health care professionals involved is small and highly specialized, and they keep a close eye on patients; and the risks of Korlym treatment can be managed through physician and patient labeling, which includes a MedGuide.

In addition, the company has instituted a homegrown "elements to ensure safe use" plan of sorts by arranging to distribute Korlym through a central pharmacy. The FDA estimates that about 5,000 patients will be eligible for the treatment, which received orphan designation in 2007. According to Corcept, about 20,000 patients in the United States have Cushing’s syndrome, which manifests in many ways and can affect every organ of the body.

The distribution arrangement will ensure "the timely, convenient and appropriate delivery of the drug to Cushing’s patients or to the health care institutions where this therapy may be initiated," the agency said, noting that retail pharmacies are unlikely to keep adequate supplies of the drug on hand for the condition and a central pharmacy will give Cushing’s patients better access.

Endogenous Cushing’s syndrome is caused by overproduction of cortisol, a steroid hormone that increases blood sugar levels, by the adrenal glands; the syndrome commonly strikes people between the ages of 25 and 40. Korlym is approved for patients with Cushing’s who have type 2 diabetes or glucose intolerance and are not candidates for surgery or who have not responded to prior surgery.

Korlym is a glucocorticoid receptor type II (GR-II) antagonist that blocks the cortisol receptor. Corcept, based in Menlo Park, Calif., is also studying mifepristone in a phase III trial as a therapy for psychotic depression. The company, which says it specializes in drugs for severe metabolic and psychiatric disorders, also has CORT 10829 in its portfolio of GR-II receptor antagonists, in studies for the prevention of antipsychotic-induced weight gain.

Though Korlym should never be used by pregnant women, pregnancy is extremely rare in Cushing’s syndrome patients because of the suppressive effect of cortisol on female reproduction, the FDA said. Nonetheless, Korlym will carry a boxed warning that the therapy will terminate a pregnancy.

Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.

02/21/12