Corcept fails primary goal in Cushing's syndrome study

Corcept Therapeutics announced that its investigational treatment for Cushing's syndrome, relacorilant, did not achieve the primary endpoint in a Phase 3 trial designed to support its FDA submission. The trial, named GRADIENT, aimed to demonstrate the efficacy of relacorilant in reducing mean systolic blood pressure in patients with Cushing's syndrome and hypertension over a 22-week period. While patients receiving relacorilant showed statistically significant improvements in mean systolic blood pressure from baseline, the difference compared to those receiving a placebo did not reach statistical significance.

As a result of this outcome, Corcept’s stock experienced a 7% drop in premarket trading. Despite this setback, relacorilant did achieve several secondary endpoints in the GRADIENT trial, including improvements in hyperglycemia and body weight. The trial focused on patients with a specific type of Cushing's syndrome caused by an adrenal adenoma or adrenal hyperplasia, as noted by CEO Joseph Belanoff during the company's third-quarter results call with investors.

Cushing's syndrome is characterized by excessive cortisol levels in the body, leading to symptoms such as weight gain and high blood pressure. In a previous study called GRACE, relacorilant met its primary endpoint. Patients who continued the drug in the GRACE study after an initial open-label phase maintained their improvements, whereas those switched to a placebo experienced a worsening of symptoms.

Bill Guyer, Corcept’s chief development officer, expressed confidence in submitting a New Drug Application (NDA) based on the GRADIENT data, while emphasizing that GRADIENT was always intended to support the pivotal data from the GRACE study. According to Guyer, the GRACE study remains the cornerstone of their submission strategy, aligning with their agreement with the FDA.

Additionally, Corcept highlighted that relacorilant was well-tolerated in the GRADIENT trial, showing no signs of side effects associated with other treatments for Cushing's syndrome. Specifically, there were no incidences of hypokalemia, endometrial hypertrophy, or related vaginal bleeding, among other potential adverse effects.

Earlier this year, Corcept faced a legal defeat in a patent dispute with Teva over its already marketed Cushing's syndrome medication, Korlym. During the investor call, Corcept's president of endocrinology, Sean Maduck, expressed optimism about relacorilant, suggesting it would surpass Korlym in effectiveness. Maduck pointed out that relacorilant does not exhibit the off-target progesterone effects associated with Korlym.

In summary, while Corcept Therapeutics encountered a challenge with the primary endpoint in the GRADIENT trial for relacorilant, the drug demonstrated positive secondary outcomes and was well-tolerated. The company remains confident in its overall strategy, supported by the pivotal GRACE study, to pursue FDA approval for this promising treatment for Cushing's syndrome, aiming to offer a better alternative to their existing therapy.