Relacorilant found safe, effective in long-term extension study
Study is assessing therapy in 116 Cushing's patients who finished other trials
Long-term treatment with relacorilant led to a sustained decrease in blood pressure, blood sugar levels, and body weight in people with Cushing’s syndrome, new data from an extension study shows.
The extension study (NCT03604198) is assessing relacorilant’s long-term safety and efficacy in 116 people with Cushing’s who completed previous trials of the therapy. Based on positive data from the extension study and previous trials, the therapy’s developer plans to ask the U.S. Food and Drug Administration (FDA) to approve it.
“With these new data from the long-term extension study of relacorilant, we are pleased to share more positive results that only reinforce the strong long-term safety and efficacy profile we’ve seen through our GRACE, GRADIENT and Phase 2 studies — all of which support our planned new drug application (NDA) for relacorilant this month,” Bill Guyer, Corcept Therapeutics’s chief development officer, said in an email to Cushing’s Disease News. “We look forward to working closely with the FDA on our submission, with the goal of delivering this novel treatment option to patients and treating physicians as quickly as possible.”
The findings were presented at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease this month in Los Angeles. The presentation was titled, “Relacorilant Improved Blood Pressure and Maintained Other Cardiometabolic Improvements in Long-term Study in Patients With Endogenous Hypercortisolism (Cushing Syndrome).”
Cushing’s syndrome comprises several conditions caused by high cortisol levels, or hypercortisolism. It’s considered endogenous when a problem within a person’s body, usually a tumor, is the underlying cause of hypercortisolism. Cushing’s disease is a specific form of endogenous Cushing’s that’s caused by tumors in the pituitary gland.
Results of studies with relacorilant
Relacorilant is an experimental oral therapy that’s designed to selectively block glucocorticoid receptors to which cortisol normally binds to exert its effects. The therapy is expected to prevent symptoms associated with high cortisol levels, including high blood pressure (hypertension) and high blood sugar.
In a completed Phase 2 trial (NCT02804750), relacorilant reduced blood pressure and blood sugar in people with endogenous Cushing’s.
In the open-label part of the Phase 3 GRACE trial (NCT03697109), patients with Cushing’s and concomitant diabetes and/or high blood pressure saw a rapid reduction of blood pressure, body weight, and blood sugar levels. The patients were then assigned to continue treatment or receive a placebo in a randomized withdrawal phase and those who remained on relacorilant maintained blood pressure control.
The patients who completed either the Phase 2 trial, GRACE, or the Phase 3 GRADIENT trial (NCT04308590), which enrolled people with adrenal Cushing’s, were eligible to roll into the long-term extension study. As of September, 116 patients had completed up to about six years of treatment.
The new results, obtained after two years of treatment, showed patients had a significant decrease in blood pressure throughout the extension, with mean systolic blood pressure dropping by 10 millimeters of mercury (mmHg) and diastolic blood pressure dropping by 7.3 mmHg. Systolic blood pressure is the blood pressure measured when the heart contracts, while diastolic blood pressure is measured while the heart relaxes between beats.
The patients who’d taken a placebo in the randomized withdrawal part of GRACE showed a reversal in their deterioration while on the placebo. This included a significant decrease in body weight and blood sugar levels, based on glycated hemoglobin (HbA1c), which measures the proportion of hemoglobin — the protein that carries oxygen in red blood cells — that is bound to blood sugar.
“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,” said Richard Auchus, MD, PhD, professor at the University of Michigan and chief of the endocrinology and metabolism section at the Veterans Affairs Medical Center in Ann Arbor, said in a company press release.
“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, said Auchus, who presented the findings at the Congress.
Relacorilant’s long-term safety is consistent with the observed profile in other trials, with most adverse events being mild to moderate in severity and no new safety issues identified. The most common side effects included pain in the back, joint, and extremities, swelling, nausea, headache, and COVID-19.
There was also a low frequency of serious adverse events, which were not dose-dependent. Relacorilant also didn’t cause other unintended off-target side effects, including vaginal bleeding and enlargement of the tissue that lines the uterus. Low levels of cortisol due to adrenal insufficiency and treatment-induced low potassium levels also were not observed.
“Relacorilant’s strong efficacy and safety profile positions the medication to become a new standard of care in treating patients with hypercortisolism,” Guyer said.
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