Getting in just under the wire on its second self-imposed deadline, Corcept Therapeutics (Nasdaq: CORT) finally announced submission of its NDA for Corlux (mifepristone) in Cushing’s Syndrome, a disease characterized by high levels of circulating cortisol resulting in glucose intolerance, hypertension, depression, and obesity. Corlux is a glucocorticoid receptor-II (GR-II) antagonist which can block the effects of the glucocorticosteroid cortisol. The company has Orphan Drug Designation for Corlux in Cushing’s Syndrome and is hoping to secure priority review if the FDA accepts their submission. There are currently no therapies approved in the United States exclusively for Cushing’s Syndrome, and care typically revolves around symptom management. Corcept believes (quite logically) that focusing on the underlying biochemical problem will be a better way of treating this disease.
Corcept announced positive Phase 3 data at the end of 2010 and beginning of 2011, with both primary and secondary endpoints being reached. The trial was conducted in two groups of Cushing’s patients who were either glucose-intolerant or hypertensive and who had failed, relapsed from, or were ineligible for surgery on cortisol-producing tumors.
The glucose intolerant group’s primary endpoint was a 25% or better improvement in glucose tolerance, and a response rate of 60% was achieved in this arm of patients. The primary endpoint for the hypertensive group was an improvement of 5mm or greater in diastolic blood pressure, and 43% of patients achieved this level. Both response rates are considered statistically significant (above the 20% “hurdle rate”), the drug was well tolerated in the trials, and no major side effects were reported. Furthermore, the secondary endpoint of “global clinical improvement” was met by 87% of patients in the study as analyzed by a data review board comprised of three academic physicians with clinical Cushing’s Syndrome experience.
Commonly observed side effects were adrenal insufficiency, endometrial thickening, and hypokalemia. The majority of serious adverse events were determined not to be drug-related, and any adverse effects that were drug-related were resolved with clinical management. It is worth noting that 88% of the patients involved in the study opted to enter into a long-term extension study, which can be seen as a vote of confidence by the patient population in Corlux’s efficacy and tolerability. Corcept plans to present detailed trial data at the Endocrine Society Annual Meeting in June which will likely allow a more comprehensive analysis of its approval odds. As of right now, Corlux’ chances look good.
Corcept originally announced plans to submit the NDA by the end of March; hopefully the two week extension needed to submit to the FDA means the company took extra care in finalizing its application. Stay tuned for updates on Corcept Therapeutics as the regulatory fate of their first clinical candidate unfolds.