Relacorilant improves cardiometabolic metrics for patients with Cushing’s syndrome
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Key takeaways:
- Relacorilant improved blood pressure and other parameters at 24 months for patients with Cushing’s syndrome.
- No new safety issues related to the drug emerged.
Among patients with endogenous hypercortisolism, relacorilant improved cardiometabolic parameters such as blood pressure, HbA1c and weight, according to results of a long-term extension study.
The phase 3, long-term extension study, presented at World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease, included 116 patients (mean age, 56.4 years; 77.6% women) with endogenous hypercortisolism (Cushing’s syndrome) taking relacorilant (Corcept Therapeutics) who had previously completed the phase 3 GRACE or GRADIENT studies or a phase 2 hypercortisolism study, Richard J. Auchus, MD, PhD, professor of pharmacology and internal medicine in the division of metabolism, endocrinology and diabetes at the University of Michigan, said during a presentation.
Patients were followed for a median of 1 year and a maximum of 6 years.
“We wanted to look at the long-term safety of the drug, but also the durability of the response,” Auchus told Healio.
He said patients being willing to stay in the study for as long as 6 years is “evidence that they feel the drug is helping them.”
At 24 months, compared with baseline, 24-hour ambulatory systolic BP dropped 10 mm Hg (P = .012) and 24-hour ambulatory diastolic BP fell 7.3 mm Hg (P = .01), according to the researchers.
In the long-term extension study, patients assigned placebo in the randomized withdrawal phase of the GRACE study, who had previously been taking relacorilant for 22 weeks, reversed the BP increases they had experienced while on placebo and experienced declines in BP beyond those observed in their earlier regimen of relacorilant, Auchus said during the presentation.
Also at 24 months, weight fell by a mean of more than 5 kg and HbA1c fell by more than 0.5 percentage points, he said.
The safety profile of relacorilant was consistent with those of prior studies, with no new safety signals identified, Auchus said. The most common adverse event was pain in an extremity (23.3%).
Six patients had treatment-emergent adverse events leading to death, but none of the deaths were related to relacorilant, he said.
“The safety profile is very good, and there was absence of some of the things we see with other treatments for hypercortisolism such as adrenal insufficiency and QT prolongation,” Auchus told Healio. “Unlike mifepristone, which is the currently available glucocorticoid receptor modulator, relacorilant does not have any progesterone receptor binding, and so there was no uterine bleeding and no endometrial hypertrophy that occurred in women during the trial. Also, [adrenocorticotropic hormone] and cortisol did not increase significantly, and hypokalemia was very rare.”
The results mean there should soon be another option for treatment of this population, Auchus told Healio.
“All the treatments for hypercortisolism, they work, but they have their disadvantages,” he said. “This one has very few disadvantages. Yet it continues to show efficacy.”
Relacorilant is not yet approved for commercial use in the United States.
For more information:
Richard J. Auchus, MD, PhD, can be reached at rauchus@med.umich.edu.
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Auchus RJ, et al. Abstract 0048. Presented at: World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease; Dec. 12-14, 2024; Los Angeles.
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