Trial data for Corcept’s relacorilant, Korlym expected next year
Company plans to submit NDA to market relacorilant in 2Q 2024
The Phase 3 GRACE trial testing relacorilant in people with Cushing’s syndrome has completed enrollment and data from it is expected next year, according to a recent corporate update from Corcept Therapeutics, its developer.
The company plans to submit a new drug application (NDA) to U.S. authorities to market the therapy for all forms of Cushing’s syndrome, including Cushing’s disease, in the second quarter of 2024.
“With enrollment in GRACE complete, we are focused on finishing the trial and preparing our NDA,” Bill Guyer, Corcept’s chief development officer, said in a company press release. “Relacorilant has tremendous promise as a treatment for patients with all types of Cushing’s syndrome and we are eager to make it available.”
In all forms of Cushing’s syndrome, patients have hypercortisolism, or too high blood levels of the hormone cortisol. The most common cause of excess cortisol is a tumor on the pituitary gland, a condition known as Cushing’s disease.
Cortisol exerts its effects by binding to glucocorticoid receptors. Because cortisol helps regulate blood sugar, hypercortisolism can lead to high blood sugar and diabetes.
GRACE, GRADIENT trials of relacorilant
Relacorilant is designed to reduce the effects of high cortisol in all forms of Cushing’s syndrome, irrespective of its underlying cause, by blocking glucocorticoid receptors.
The GRACE trial (NCT03697109) has enrolled about 130 Cushing’s patients with type 2 diabetes, impaired glucose tolerance (high blood sugar), and/or high blood pressure. For the first 22 weeks (about five months), all its participants are being treated with oral relacorilant capsules at 100-400 mg/day based on tolerability. The target dose is 400 mg.
Those who respond to the therapy based on predefined criteria related to blood sugar and blood pressure will be randomly assigned to relacorilant or a placebo for 12 more weeks (three months), when blood sugar and blood pressure will be evaluated again.
All of them will be able to continue with relacorilant in the study’s open-label extension phase. Those who don’t respond to treatment in the first 22 weeks may be able to continue treatment directly in the extension phase.
Meanwhile, the Phase 3 GRADIENT trial (NCT04308590) of relacorilant in patients with Cushing’s caused by adrenal adenomas, tumors in the adrenal glands that produce cortisol, is almost finished enrolling. It has been recruiting up to 130 participants at sites in the U.S., Europe, and Israel.
Participants will be randomly assigned to relacorilant, at a target dose of 400 mg, or a placebo for 22 weeks. The goal is to evaluate the treatment’s effect on blood sugar and blood pressure, and patients will be able to enter an open-label extension once the trial is completed.
“Our GRADIENT trial will produce valuable data about an etiology [disease form] of Cushing’s syndrome that affects many patients whose hypercortisolism frequently goes undiagnosed and untreated,” Guyer said.
Phase 4 trial of Korlym is recruiting
Corcept also markets Korlym (mifepristone), a glucocorticoid receptor blocker approved for high blood sugar in adults with Cushing’s syndrome who have glucose intolerance or type 2 diabetes and for whom surgery was ineffective or not an option.
A Phase 4 trial called CATALYST (NCT05772169) is recruiting up to 1,000 people in the U.S. with difficult to control type 2 diabetes despite treatment.
The study has two goals. In its first part, the participants will be screened for hypercortisolism. For those patients, excess cortisol could in part be the underlying cause of the uncontrollable high blood sugar.
“CATALYST is the largest study ever conducted to establish the prevalence of hypercortisolism in patients with difficult to control diabetes,” Guyer said. “We expect that it will further enable physicians to identify and provide effective treatment for a substantial group of patients with Cushing’s syndrome, whose condition, in most cases, now goes undiagnosed.”
Those found to have hypercortisolism will enter the second phase, where they’ll be randomly assigned to Korlym or a placebo for about six months. The effects on blood sugar levels will be evaluated.
“Korlym is an excellent treatment for patients with Cushing’s syndrome and there are many eligible patients who have yet to receive it,” said Joseph K. Belanoff, MD, Corcept’s CEO.
Enrollment in CATALYST is “progressing ahead of schedule,” Guyer said. “We have received very positive feedback from leading endocrinologists regarding this study and expect to complete enrollment in the fourth quarter.”
Data from GRACE, GRADIENT, and CATALYST are all expected next year.
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