Promising Six-Year Data Support Relacorilant as a New Cushing Syndrome Therapy

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Corcept Therapeutics shared results from a phase 3 long-term, open-label extension study of relacorilant in patients with endogenous hypercortisolism (Cushing syndrome). The study demonstrated durable cardiometabolic improvements, including reductions in blood pressure, and confirmed relacorilant’s safety and tolerability over six years.

Relacorilant, a selective cortisol modulator, works by binding to the glucocorticoid receptor while avoiding the body’s other hormone receptors. Because of this unique mechanism of action, patients treated with the drug did not experience increases in cortisol concentrations, adrenal insufficiency or relacorilant-induced irregular vaginal bleeding with endometrial hypertrophy.

“These data will support relacorilant’s new drug application (NDA), which we plan to submit this month,” Bill Guyer, Pharm.D., Corcept’s chief development officer, said in a statement. “Relacorilant’s strong efficacy and safety profile positions the medication to become a new standard of care in treating patients with hypercortisolism.”

Cushing syndrome is caused by excessive cortisol activity or taking glucocorticoids, with symptoms including hypertension, central obesity, difficult-to-control type 2 diabetes, elevated blood sugar, weak muscles and extreme fatigue. Patients may develop a fatty hump between the shoulders, stretch marks and a rounded face (sometimes referred to as “moon face”) and may bruise easily. These patients may also experience cognitive issues, anxiety, depression and irritability. This condition, which can impact every organ system, can be deadly if left untreated or managed poorly.

A group of 116 patients with hypercortisolism were recruited into the long-term study and followed for up to six years. These patients had previously completed either Corcept’s phase 3 GRACE or GRADIENT studies or its phase 2 trial evaluating hypercortisolism.

Results, which were presented at the World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease (WCIRDC), demonstrated the potential benefits of treatment with relacorilant to treat Cushing syndrome.

Patients showed significant reductions in systolic (10.0 mm Hg) and diastolic (7.3 mm Hg) blood pressure at 24 months compared with their baseline measurements at enrollment. Additionally, continued glycemic control, weight stabilization and maintenance of other cardiometabolic measures were observed.

Those who resumed relacorilant after placebo experienced both a reversal of deterioration and further improvement beyond blood pressure measurements at entry. To confirm the accuracy of assessments, participants’ blood pressure was measured by 24-hour ambulatory blood pressure monitoring.

Throughout the six-year study duration, relacorilant maintained a favorable safety profile, which is consistent with relacorilant’s known safety profile. The majority of adverse events were rated as mild to moderate in severity, with few serious adverse events reported. The most common side effects included pain in the extremities, back pain, nausea, headache and arthralgia. No new safety signals were identified.

“People living with hypercortisolism are at risk of serious cardiometabolic comorbidities, including hypertension and hyperglycemia,” Richard Auchus, M.D., Ph.D., professor of internal medicine in the Division of Metabolism, Endocrinology and Diabetes at the University of Michigan and chief of the Endocrinology and Metabolism Section at the Ann Arbor VA Medical Center, said in a statement. “These long-term data demonstrate significant improvements across a broad set of signs and symptoms of hypercortisolism without the toxicities observed with current treatment options. It is especially encouraging to see data from patients treated for up to six years that show progressive reductions in blood pressure, maintenance of cardiometabolic improvements, and long-term drug tolerability.”

The team at Corcept is currently evaluating treatment with relacorilant for other serious disorders, including adrenal, ovarian and prostate cancer.