Corcept Therapeutics has announced positive long-term results from its Phase III open-label extension study of relacorilant in patients with endogenous hypercortisolism, also known as Cushing's syndrome. The study, presented at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease (WCIRDC), demonstrated durable cardiometabolic improvements and good tolerability over a treatment period of up to six years.
The extension study enrolled 116 patients who had previously participated in the GRACE, GRADIENT, or Phase II trials. These patients experienced sustained improvements in blood pressure and maintained positive responses in other cardiometabolic parameters, including body weight and glycemic control.
Significant Blood Pressure Reductions
After 24 months, patients showed statistically significant reductions in mean systolic blood pressure (10.0 mm Hg; p-value: 0.012) and mean diastolic blood pressure (7.3 mm Hg; p-value: 0.016) compared to baseline measurements at the start of the extension study. Notably, patients who had been switched to placebo during the GRACE study and subsequently resumed relacorilant not only reversed the deterioration seen on placebo but also achieved additional improvements beyond their initial blood pressure measurements.
To ensure accuracy, blood pressure was monitored using 24-hour ambulatory blood pressure monitoring.
Mechanism of Action and Clinical Implications
Relacorilant is a selective cortisol modulator designed to target the glucocorticoid receptor without affecting other hormone receptors. This specificity is believed to contribute to its favorable safety profile and efficacy in managing hypercortisolism.
According to Corcept Therapeutics chief development officer Bill Guyer, the long-term extension study results align with previous findings from the GRACE, GRADIENT, and Phase II studies. He stated that these data would support the new drug application (NDA) for relacorilant, which the company plans to submit this month. Guyer also expressed confidence that relacorilant's efficacy and safety profile position it as a potential new standard of care for patients with hypercortisolism.
Ongoing Research and Future Directions
In addition to Cushing's syndrome, Corcept is investigating relacorilant for its potential in treating various cancers, including ovarian, adrenal, and prostate cancer. The therapy is protected by several patents and has received orphan drug designation in both the US and the European Union.
