First medication approved by FDA for patients with endogenous Cushing's syndrome

FDA has approved the first medication therapy, mifepristone (Korlym, Corcept Therapeutics), for endogenous Cushing’s syndrome, a condition that, left untreated, has a mortality rate of 50% after 5 years.

The 300-mg tablets are taken once daily to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing’s syndrome who have diabetes mellitus type 2 or glucose intolerance and have failed surgery or are not candidates for surgery.

Korlym should never be used (contraindicated) by pregnant women, FDA warned in its news release.

The medication will be available by May 1 through a distribution system designed to support both patients and prescribers. Corcept has begun hiring Medical Science Liaisons to inform practitioners about the drug, which will be dispensed by CuraScript SP, a subsidiary of Express Scripts.

Korlym blocks the glucocorticoid receptor type II (GR-II) to which cortisol normally binds. By blocking this receptor, Korlym inhibits the effects of excess cortisol in Cushing’s syndrome patients.

Pregnancy is an extremely rare occurrence in Cushing's syndrome patients because of the suppressive effect of excess cortisol on female reproductive function. However, Korlym will carry a boxed warning advising healthcare professionals and patients that the therapy will terminate a pregnancy.

FDA has determined that a Risk Evaluation and Mitigation Strategy (REMS) is not necessary for Korlym to ensure that the benefits outweigh the risks for patients with endogenous Cushing's syndrome.

“Korlym is a significant advance in the treatment of patients suffering from the debilitating symptoms of Cushing’s syndrome,” Robert L. Roe, MD, Corcept’s president, said in a company press release. “For the first time, these patients have access to an approved therapy when surgery has failed or is not an option.”

Korlym clinical trial investigator Amir Hamrahian, MD, department of endocrinology, diabetes and metabolism at the Cleveland Clinic, said in the press release that surgery, usually the first-line treatment for patients with Cushing’s syndrome, “is not always successful and not all patients are candidates.”

Hamrahian said he has used Korlym successfully as part of clinical trials. “My patients continue to do well on the medicine …. This medicine’s approval gives me a much needed tool to better treat patients.”

The clinical data supporting FDA approval of Korlym resulted from an uncontrolled, open-label, multicenter, 24-week phase 3 study of 50 patients who had endogenous Cushing's syndrome and were either not eligible for or had relapsed from surgery and were either glucose intolerant (29 patients) or had hypertension (21 patients).

Within the glucose intolerant group, 60% of patients had a greater than 25% reduction from baseline in the area under the curve in the oral glucose tolerance test. In this group, mean hemoglobin A_1C (HbA_1C) was reduced from 7.4% to 6.3%. All 14 patients with above-normal HbA_1C levels at baseline experienced reductions. Eight of these 14 normalized their HbA_1C. Antidiabetic medications were reduced in 7 of the 15 patients with diabetes mellitus type 2 and remained constant in the others.

Patients who responded to therapy were allowed enrollment in an extension trial. Eighty-eight percent of the patients who completed the trial chose to do so.

A peer-reviewed analysis of the study results will soon be published in a leading journal, Corcept said.

Endogenous Cushing's syndrome is a serious, debilitating and rare multisystem disorder. It is caused by the overproduction of cortisol (a steroid hormone that increases blood sugar levels) by the adrenal glands. Cushing’s syndrome occurs in about 20,000 people in the United States, mostly women between the ages of 20 and 50.

About 5,000 patients will be eligible for Korlym treatment, which received an orphan drug designation by FDA in 2007. More than 70% of Cushing’s syndrome patients suffer from glucose intolerance or diabetes.