Corcept Therapeutics Incorporated announced positive results from the open-label portion of the pivotal Phase 3 GRACE trial of its proprietary selective cortisol modulator relacorilant in patients with all etiologies of endogenous Cushing?s syndrome (hypercortisolism). GRACE has two parts. In the open-label phase, 152 patients with Cushing?s syndrome and either hypertension, hyperglycemia or both received relacorilant for 22 weeks.

Patients who exhibited pre-specified improvements in either or both symptoms were given the opportunity to enter the trial?s randomized, double-blind withdrawal phase, in which half of the patients continued to receive relacorilant and half received placebo for 12 weeks. GRACE?s primary endpoint is maintenance of blood pressure control in the randomized withdrawal phase, with maintenance of glycemic control as the key secondary endpoint. Other key secondary and exploratory endpoints in the randomized withdrawal phase include changes in weight, waist circumference, cognitive impairment and Cushing?s Quality of Life score.

The data provided below are from GRACE?s open-label phase. Open-Label Results: Patients in the open-label phase exhibited clinically meaningful and statistically significant improvements in hypertension, hyperglycemia and other key secondary and exploratory endpoints. The drug was well-tolerated, consistent with relacorilant?s known safety profile.

Due to relacorilant?s unique mechanism of action, the observed efficacy was seen without increases in cortisol concentrations and relacorilant-induced hypokalemia. In addition, no cases of relacorilant-induced endometrial hypertrophy with or without vaginal bleeding were seen, nor were there any instances of adrenal insufficiency or QT prolongation (independently confirmed). Hypertension: Rapid and sustained improvements in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were observed in all patients with hypertension, with an improvement in mean SBP of 7.9 mm Hg and mean DBP of 5.4 mm Hg at 22 weeks (p-values: <0.0001).

During the open-label phase, 63% of patients with hypertension met the study?s response criteria. For the patients that entered the randomized withdrawal phase, the observed improvements in hypertension were even greater, with improvements in mean SBP of 12.6 mm Hg and mean DBP of 8.3 mm Hg at 22 weeks (p-values: <0.0001). To ensure accuracy, hypertension was measured by 24-hour ambulatory blood pressure monitoring (ABPM).

Hyperglycemia: Glucose metabolism was measured by several diagnostic tests, including the oral glucose tolerance test (glucose area under the curve or AUCglucose), hemoglobin A1C (HbA1c) and fasting glucose. Clinically meaningful and statistically significant improvements in glucose metabolism were observed for all patients with hyperglycemia, which includes patients with diabetes and impaired glucose tolerance (pre-diabetes). Data showed improvements in mean AUCglucose of 3.3 h mmol/L, mean HbA1c of 0.3% and mean fasting glucose of 12.4 mg/dL at 22 weeks (p-values: <0.0001, 0.03, 0.03, respectively).

During the open-label phase, 50% of patients with hyperglycemia met the study?s response criteria. For the patients that entered the randomized withdrawal phase, the observed improvements in hyperglycemia were even greater, with improvements in mean AUCglucose of 6.2 h mmol/L, mean HbA1c of 0.7% and mean fasting glucose of 25.2 mg/dL at 22 weeks (p-values: <0.0001, <0.0001, 0.006, respectively). Other Cushing?s Syndrome Symptoms: Statistically significant improvements in other symptoms of Cushing?s syndrome, including body weight, waist circumference, cognition (as assessed by the Trail Making Test) and Cushing?s Quality of Life score, were observed in all patients during the open-label phase of the study (all p-values: <0.0001).

Safety: Relacorilant was well tolerated. The most common adverse events were mild-to-moderate nausea, edema, pain in extremities and back, and fatigue, which are symptoms consistent with the cortisol withdrawal many patients experience following surgery or initiation of medical therapy to treat hypercortisolism. There were no increases in cortisol concentrations and relacorilant-induced hypokalemia.

In addition, no cases of relacorilant-induced endometrial hypertrophy with or without vaginal bleeding, adrenal insufficiency or QT prolongation (independently confirmed) were reported.