Corcept planning to seek relacorilant approval for Cushing’s in 2024
Enrollment in the Phase 3 GRACE trial anticipated to be completed soon
The Phase 3 GRACE trial that’s testing relacorilant in people with Cushing’s syndrome is expected to finish enrolling participants in the coming weeks, according to a recent corporate update from its developer, Corcept Therapeutics.
Assuming the trial’s findings are positive, Corcept expects to use its data as the basis for relacorilant’s approval, in the form of a new drug application (NDA), in the U.S. in the first half of 2024.
Cushing’s syndrome is marked by excess levels of the stress hormone cortisol, called hypercortisolism. Cushing’s disease is a subtype of the syndrome that’s caused by a tumor in the pituitary gland. Relacorilant is designed to reduce the effects of high cortisol levels by blocking receptors the hormone normally binds with to exert its effects.
The GRACE trial (NCT03697109) is expected to enroll about 130 people with Cushing’s syndrome who have type 2 diabetes, impaired glucose tolerance, and/or high blood pressure. For the first 22 weeks (about six months) of the study, all the participants will be treated with relacorilant, starting at a dose of 100 mg/day and increased up to 400 mg/day, based on tolerability.
After the first 22 weeks, they will be evaluated to see if they responded to the therapy based on predefined criteria regarding blood sugar and blood pressure. Those who respond will be randomly assigned to take either relacorilant or a placebo for another 12 weeks, the goal being to assess whether switching to a placebo blunts the treatment response.
Those who don’t show a response at 22 weeks may have the option to continue receiving relacorilant in the study’s open-label extension phase. Those who complete the 12-week placebo-controlled portion also can continue receiving active treatment into the extension.
Other studies of relacorilant
Corcept is also conducting another Phase 3 study called GRADIENT (NCT04308590) to compare relacorilant against a placebo in about 130 adults with Cushing’s syndrome caused by an adrenal adenoma (a tumor in the adrenal glands). Participants will receive relacorilant or a placebo for 22 weeks to assess the effect on predefined blood sugar and blood pressure parameters. GRADIENT is still enrolling participants at sites in the U.S., Europe, and Israel.
“In the next  months we expect data from our GRACE, GRADIENT and … submission of the NDA for relacorilant in Cushing’s syndrome,” Joseph Belanoff, MD, CEO of Corcept, said in a company press release.
Corcept is also working to develop Korlym (mifepristone), the company’s approved therapy for high blood sugar (hyperglycemia) in adults with Cushing’s syndrome who have type 2 diabetes or glucose intolerance and for whom curative surgery failed or isn’t an option.
“Korlym is an excellent treatment for patients with Cushing’s syndrome and there are many eligible patients who have yet to receive it,” Belanoff said. “We are making substantial investments to improve the ability of physicians to identify and treat patients with hypercortisolism, most notably our recently established CATALYST study, and are optimistic about the growth of our Cushing’s syndrome business.”
The company’s CATALYST (NCT05772169) aims to enroll 1,000 people with type 2 diabetes that’s difficult to control with available therapies.
In the first part of the Phase 4 study, patients will be screened for hypercortisolism. Those found to have hypercortisolism can enter the second portion, where they’ll be given either Korlym or a placebo for about six months.
“Independent studies conducted over the last  years have found that the prevalence of hypercortisolism in patients with type 2 diabetes is substantially higher than in the general population,” said Bill Guyer, Corcept’s chief development officer. “CATALYST identifies patients whose diabetes is caused by hypercortisolism and offers them a placebo-controlled study where Korlym is the active treatment.
Enrollment is expected to be complete by the end of the year, Guyer said.