MENLO PARK, CA--(Marketwire - April 09, 2012) - The results of Corcept Therapeutics Incorporated's phase 3 SEISMIC trial published in The Journal of Clinical Endocrinology and Metabolism (JCEM) demonstrated that refractory Cushing's syndrome patients receiving Korlym (mifepristone) experienced significant clinical improvement.
The U.S. Food and Drug Administration (FDA) recently approved Korlym as a once-daily oral medicine to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery. Korlym is the first FDA-approved therapy for endogenous Cushing's syndrome.
"The recently published SEISMIC study showed that Korlym significantly improved diabetes control (blood glucose levels, insulin sensitivity and Hemoglobin A1C), promoted weight loss and decreases in waist circumference, and improved body composition, mood and cognition in patients with Cushing's syndrome," said Maria Fleseriu, M.D., F.A.C.E., Director Northwest Pituitary Center, Oregon Health & Science University, Associate Professor of Medicine & Neurological Surgery, a principal investigator in the study. "Although clinically significant adrenal insufficiency is a potential side effect of glucocorticoid receptor antagonism, it was uncommon during this study."
"Glucocorticoid receptor antagonism with Korlym offers a new and exciting approach to control the clinical manifestations of this severe, debilitating disease," Dr. Fleseriu added. "The side effect profile over 6 months is well characterized and manageable with close follow-up."
Physicians and patients seeking more information can visit http://www.korlymspark.com.
The Commercialization of Korlym
Corcept's guiding principle is that every patient who is prescribed Korlym will receive it. "Our mission is to get medicine to patients who need it," said Joseph K. Belanoff, M.D., the company's Chief Executive Officer. "Corcept's Support Program for Access and Reimbursement for Korlym (SPARK) will provide patients with a case manager who can help them navigate their medical coverage on a case by case basis and identify the Corcept support programs available to them."
The SEISMIC Study
Fifty Cushing's syndrome patients were enrolled in the study. Forty-three had Cushing's disease (an ACTH-producing tumor of the pituitary gland), of which 42 had prior surgery, four patients had ectopic ACTH-producing tumors and three had adrenal cancer. Of the 29 patients enrolled in the study who were glucose intolerant, 60% (p < 0.0001) met the study's primary endpoint, defined as a 25% or greater reduction in blood sugar level on a standard oral glucose tolerance test from baseline to 24 weeks. In these patients there was a continued improvement in glucose tolerance measured at each of the evaluations at week 6, 10, and 16, as well as at week 24. Of the 12 patients taking insulin at baseline, seven cut their daily dose by at least 50%. There was also a statistically significant reduction in mean HbA1c over the course of the study, from 7.43% at baseline to 6.29% at study conclusion (p < 0.001). Of the twelve patients who had an HbA1c over 7% at baseline (mean = 8.5%), nine achieved an HbA1c below 7%, including six who achieved an HbA1c of 6% or below.
All patients were evaluated on the key secondary endpoint of "global clinical improvement" as determined by an independent data review board's evaluation of eight clinical areas - glucose, blood pressure, lipids, weight and body composition, appearance, strength, bone, psychiatric and quality of life measures. Eighty-seven percent of the patients (p < 0.0001) were judged to have made significant clinical improvement by the data review board.
The study examined patients weight gain/loss during the 24-week trial, with over half of study participants experiencing weight loss of at least 5%, compared to baseline (p < 0.001). Patients demonstrated a mean reduction in waist circumference compared to baseline -- 6.8 cm in women and 8.4 cm for men (p < 0.001 for each gender).
Side-effects observed in the phase 3 study were consistent with the safety profile of Korlym's active ingredient, mifepristone. The majority of adverse events were considered to be mild or moderate, with fatigue and nausea being the ones most commonly reported.
Approximately 90% of the patients who completed the study chose to continue as part of Corcept's extension study.
About Cushing's Syndrome
Endogenous Cushing's syndrome is a rare and life-threatening endocrine disorder that results from long-term exposure to excess levels of the hormone cortisol. This excess is caused by tumors that usually occur in the pituitary or adrenal glands that over-produce, or prompt the over-production of, cortisol.
Although cortisol at normal levels is essential to health, in excess it causes a variety of problems, including glucose intolerance and diabetes, upper body obesity, a rounded face, stretch marks on the skin, an accumulation of fat on the back, thin and easily bruised skin, muscle weakness, bone weakness, persistent infections, high blood pressure, fatigue, irritability, anxiety, psychosis and depression. Women may have menstrual irregularities and facial hair growth, while men may have decreased fertility or erectile dysfunction. More than 70 percent of Cushing's syndrome patients suffer from glucose intolerance or diabetes.
If left untreated, Cushing's syndrome has a five-year mortality rate of 50 percent.
About Korlym™ (mifepristone) 300 mg Tablets
Korlym is a once-daily oral medication that 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.
The FDA-approved labeling instructs physicians to titrate each patient's Korlym dose to clinical efficacy by assessing tolerability and degree of improvement in Cushing's syndrome manifestations. In the first six weeks, these manifestations may include changes in glucose control, anti-diabetic medication requirements, insulin levels and psychiatric symptoms. After two months, assessment may also be based on improvements in cushingoid appearance, acne, hirsutism, striae or decreased body weight, along with further changes in glucose control.
The FDA has designated Korlym as an Orphan Drug, a special status designed to encourage the development of medicines for rare diseases and conditions. Because Korlym is an Orphan Drug, Corcept will have marketing exclusivity for the FDA-approved indication until February 2019.
IMPORTANT SAFETY INFORMATION
WARNING: TERMINATION OF PREGNANCY
See full prescribing information for complete boxed warning.
Mifepristone has potent antiprogestational effects and will result in the
termination of pregnancy. Pregnancy must therefore be excluded before the
initiation of treatment with Korlym, or if treatment is interrupted for
more than 14 days in females of reproductive potential.
- Use of simvastatin or lovastatin and CYP 3A substrates with narrow therapeutic range
- Concurrent long-term corticosteroid use
- Women with history of unexplained vaginal bleeding
- Women with endometrial hyperplasia with atypia or endometrial carcinoma
Warnings and Precautions
- Adrenal insufficiency: Patients should be closely monitored for signs and symptoms of adrenal insufficiency.
- Hypokalemia: Hypokalemia should be corrected prior to treatment and monitored for during treatment.
- Vaginal bleeding and endometrial changes: Women may experience endometrial thickening or unexpected vaginal bleeding. Use with caution if patient also has a hemorrhagic disorder or is on anti-coagulant therapy.
- QT interval prolongation: Avoid use with QT interval-prolonging drugs or in patients with potassium channel variants resulting in a long QT interval.
- Use of Strong CYP3A Inhibitors: Concomitant use can increase mifepristone plasma levels significantly. Use only when necessary and limit mifepristone dose to 300 mg.
Most common adverse reactions in Cushing's syndrome ( ≥ 20%): nausea, fatigue, headache, decreased blood potassium, arthralgia, vomiting, peripheral edema, hypertension, dizziness, decreased appetite, endometrial hypertrophy.
To report suspected adverse reactions, contact Corcept Therapeutics at 1-855-844-3270 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
- Drugs metabolized by CYP3A: Administer drugs that are metabolized by CYP3A at the lowest dose when used with Korlym.
- CYP3A inhibitors: Caution should be used when Korlym is used with strong CYP3A inhibitors. Limit mifepristone dose to 300 mg per day when used with strong CYP3A inhibitors.
- CYP3A inducers: Do not use Korlym with CYP3A inducers.
- Drugs metabolized by CYP2C8/2C9: Use the lowest dose of CYP2C8/2C9 substrates when used with Korlym.
- Drugs metabolized by CYP2B6: Use of Korlym should be done with caution with bupropion and efavirenz.
- Hormonal contraceptives: Do not use with Korlym.
Use in Specific Populations
- Nursing mothers: Discontinue drug or discontinue nursing.
Please see the accompanying full Prescribing Information including boxed warning at www.corcept.com/prescribinginfo.pdf
Please see the accompanying Medication Guide at www.corcept.com/medicationguide.pdf
About Corcept Therapeutics Incorporated
Corcept is a pharmaceutical company engaged in the discovery, development and commercialization of drugs for the treatment of severe metabolic and psychiatric disorders. Korlym, a first generation GR-II antagonist, is the company's first FDA-approved medication. The company has a portfolio of new selective GR-II antagonists that block the effects of cortisol but not progesterone. Corcept owns an extensive intellectual property portfolio covering the use of GR-II antagonists, including mifepristone, in the treatment of a wide variety of psychiatric and metabolic disorders. The company also holds composition of matter patents for its selective GR-II antagonists.
Statements made in this news release, other than statements of historical fact, are forward-looking statements. Forward-looking statements are subject to a number of known and unknown risks and uncertainties that might cause actual results to differ materially from those expressed or implied by such statements. For example, there can be no assurances that clinical results will be predictive of real-world use, or regarding the pace of Korlym's acceptance by physicians and patients, the reimbursement decisions of government or private insurance payers, the effects of rapid technological change and competition, the protections afforded by Korlym's Orphan Drug Designation or by Corcept's other intellectual property rights, and the cost, pace and success of Corcept's other product development efforts. These and other risks are set forth in the Company's SEC filings, all of which are available from our website (www.corcept.com) or from the SEC's website (www.sec.gov). We disclaim any intention or duty to update any forward-looking statement made in this news release.