GRACE trial testing relacorilant in Cushing’s meets primary goal
Drop in high blood pressure sustained for 3 more months with treatment
Among people with endogenous Cushing’s syndrome whose high blood pressure, or hypertension, dropped after five months on relacorilant, that response was maintained when the patients continued treatment for an additional period of three months.
That’s according to new data from the randomized withdrawal phase of the Phase 3 GRACE trial (NCT03697109) — which was testing the oral therapy in more than 150 people with the disease — that’s now been announced by Corcept Therapeutics, relacorilant’s developer.
Specifically, it was found that patients who continued treatment with relacorilant were 83% less likely to have their blood pressure rise or require increases or changes in their blood pressure-lowering medications, as compared with those who switched to a placebo during the trial’s randomized withdrawal phase.
With the trial’s primary goal now met, Corcept is planning to submit an application, in the third quarter of this year, or by the end of September, seeking approval of relacorilant for Cushing’s syndrome.
“GRACE’s clearly positive results are a welcome development for patients and constitute a significant step toward our new drug application for relacorilant,” Bill Guyer, Corcept’s chief development officer, said in a company press release.
“Patients receiving relacorilant exhibited rapid and sustained improvements in hypertension and were 5.9 times more likely to maintain their hypertension response compared to patients receiving placebo,” Guyer said.
GRACE trial tested therapy in over 150 endogenous Cushing’s patients
Cushing’s syndrome is an umbrella term for conditions driven by excess levels of the hormone cortisol — also referred to as hypercortisolism. It is considered endogenous when the underlying cause of hypercortisolism is a problem within a person’s own body. Cushing’s disease is a specific form of endogenous Cushing’s syndrome caused by tumors in the brain’s pituitary gland.
Relacorilant is designed to selectively block glucocorticoid receptors, which are the protein receptors to which cortisol binds to exert its effects. The therapy thus is expected to prevent the symptoms associated with high cortisol levels, particularly hypertension and high blood sugar levels.
A Phase 1 trial conducted in the U.K. had first found the therapy to be generally safe and well tolerated in healthy volunteers. A Phase 2 trial (NCT02804750) then showed relacorilant to reduce blood pressure and improve glucose tolerance in people with Cushing’s patients.
Now, the GRACE trial, a Phase 3 study, is assessing the safety and efficacy of relacorilant in 152 patients with endogenous Cushing’s, with type 2 diabetes mellitus or impaired glucose tolerance (pre-diabetes), and/or uncontrolled hypertension.
This trial included an open-label phase, during which patients would receive relacorilant once daily, at doses starting at 100 mg and going up to 400 mg, for 22 weeks, or about five months. That was followed by a randomized withdrawal phase. During that second part of the study, patients who responded to the therapy would be randomly assigned to continue treatment with relacorilant or receive a placebo, for an additional period of 12 weeks, or about three months.
During the open-label portion of the trial, patients experienced a rapid and sustained reduction in hypertension, with 63% — nearly two-thirds — meeting the criteria to be considered responders. Patients with high blood sugar levels also showed clinically meaningful and statistically significant improvements in glucose metabolism during the initial phase of the trial.
The therapy also was found to ease other Cushing’s symptoms, including excessive body weight, waist circumference, and cognition issues, as well as to improve patients’ quality of life.
Relacorilant safe, well tolerated in both phases of GRACE trial
Newly-announced data from the randomized withdrawal phase showed the trial met its main goal, with patients who remained on relacorilant being significantly less likely to lose blood pressure control when compared with those who switched to a placebo in that phase.
The data from GRACE make a compelling case for the use of relacorilant in patients with endogenous hypercortisolism. … That patients experienced clinically significant improvements in hypertension, hyperglycemia [high blood sugar] and the other signs and symptoms of Cushing’s syndrome, without significant safety burden, is greatly encouraging for physicians and the patients they seek to help.
Relacorilant also was found to be safe and generally well tolerated in both phases of the GRACE trial.
“The data from GRACE make a compelling case for the use of relacorilant in patients with endogenous hypercortisolism,” said Rosario Pivonello, MD, PhD, professor at the Università Federico II di Napoli, in Italy, and GRACE’s principal investigator.
“That patients experienced clinically significant improvements in hypertension, hyperglycemia [high blood sugar] and the other signs and symptoms of Cushing’s syndrome, without significant safety burden, is greatly encouraging for physicians and the patients they seek to help,” Pivonello added.
Data from both the open-label and the randomized withdrawal phases of GRACE will be presented at the Endocrine Society (ENDO) annual meeting, to be held June 1-4, in Boston, and the Heart in Diabetes (HiD) conference, taking place June 7-9, in Philadelphia.
About the Author
