Corcept Therapeutics has announced that its Phase III GRADIENT trial of relacorilant for Cushing's syndrome, caused by adrenal gland pathology, did not meet its primary endpoint. The randomized, double-blind trial, conducted across the US, Europe, and Israel, involved 137 patients and aimed to assess the improvement in systolic blood pressure (SBP) over 22 weeks compared to placebo.
GRADIENT Trial Results
While patients treated with relacorilant experienced a mean SBP reduction of 6.6 mm Hg from baseline compared to a 2.1 mm Hg reduction in the placebo group, the difference was not statistically significant. However, the trial did achieve some secondary endpoints. Patients on relacorilant showed clinically meaningful and statistically significant improvements in hypertension, hyperglycemia, weight, and body composition compared to their baseline measurements, whereas the placebo group did not experience similar improvements.
Tolerability and Safety Profile
Notably, relacorilant was well-tolerated during the GRADIENT trial. Corcept Therapeutics reported no instances of relacorilant-induced hypokalemia, endometrial hypertrophy or related vaginal bleeding, adrenal insufficiency, or QT prolongation, addressing some concerns associated with existing treatments.
Implications for NDA Submission
Corcept Therapeutics plans to submit a New Drug Application (NDA) for relacorilant by the end of the year, supported by data from both the GRADIENT and GRACE trials. The GRACE trial, which involved 152 patients, met its primary endpoint related to the loss of hypertension control during the randomized-withdrawal phase.
Expert Commentary
According to Corcept Therapeutics’ chief development officer, Bill Guyer, the positive results observed in the GRADIENT trial confirm relacorilant's potential as a significant advancement in treating Cushing's syndrome. He emphasized that patients receiving relacorilant experienced clinically meaningful improvements across a range of hypercortisolism signs and symptoms, without the serious adverse effects sometimes seen with currently approved treatments. Guyer believes that the GRADIENT data will strengthen relacorilant’s NDA submission.
About Cushing's Syndrome
Cushing’s syndrome results from prolonged exposure to elevated levels of cortisol. It often affects individuals using steroid medications, which contain synthetic cortisol. The condition is characterized by increased fat accumulation (particularly in the neck and shoulders), facial changes, stretch marks, easily bruised skin, and hypertension. The GRADIENT trial sought to address hypertension, a common and significant comorbidity in Cushing's syndrome patients.
