Relacorilant safe, works to control high blood pressure in Cushing’s: Study
Full data support therapy's use for patients with excess cortisol, per developer
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Relacorilant, an oral treatment being developed by Corcept Therapeutics, appears to be safe and effective for controlling high blood pressure caused by hypercortisolism, or excess cortisol, in adults with endogenous Cushing’s syndrome, including Cushing’s disease.
That’s according to GRACE (NCT03697109), an international Phase 3 clinical study that evaluated the safety and efficacy of relacorilant compared with a placebo in more than 150 patients. Its goal was to determine if the experimental therapy worked to maintain blood pressure control.
Early data had already shown that relacorilant helped control hypertension, or high blood pressure, in people with Cushing’s. The therapy also reduced high blood sugar and helped patients lose weight.
Full data now confirm that individuals given relacorilant “were more likely to maintain hypertension control compared with patients treated with [the] placebo,” per the study.
The researchers said these findings “support consideration of relacorilant as a therapeutic option to reduce the harmful and debilitating effects of endogenous hypercortisolism.”
The study, “Efficacy and safety of relacorilant for the treatment of patients with Cushing’s syndrome (GRACE): a multicentre, phase 3, double-blind, placebo-controlled, randomised-withdrawal study,” was published in The Lancet Diabetes & Endocrinology. It was funded by Corcept.
In endogenous Cushing’s syndrome, the body produces excessive amounts of cortisol due to internal dysfunction. When in excess, this hormone can cause symptoms such as high blood pressure, or hypertension, and high blood sugar, known as hyperglycemia. In Cushing’s disease, excess cortisol production is caused by a tumor in the brain’s pituitary gland.
Relacorilant is designed to counter the effects of excess cortisol in the body. It works by blocking the glucocorticoid receptor, a protein to which cortisol binds in order to produce its effects. By competing with cortisol for this receptor, relacorilant reduces cortisol’s activity, which is expected to ease Cushing’s symptoms.
FDA rejected relacorilant in January decision
Earlier this year, the U.S. Food and Drug Administration (FDA) declined to approve relacorilant to treat adults with Cushing’s syndrome experiencing hypertension. The regulatory agency found that available data did not clearly show that the treatment’s benefits outweigh its risks. Corcept plans to meet with the FDA to determine what additional data are needed for possible approval.
The company’s application was based on data from the GRACE study, which included 152 patients diagnosed with Cushing’s syndrome. During the first part of the study, all patients received relacorilant once daily by mouth as capsules for 22 weeks, or about five months. The dose was gradually increased from 100 mg to a maximum of 400 mg, depending on tolerance and response.
Patients who showed improvement were then randomly assigned to either continue relacorilant or switch to a placebo for 12 weeks, or about three months. This design, called randomized withdrawal, helps determine whether the treatment is truly responsible for any improvements seen. The main outcome measured was whether patients lost control of their high blood pressure during this phase.
A total of 95 patients completed the first part of the study, and 62 met the response criteria and entered the randomized withdrawal part. Among those randomized, 30 continued relacorilant and 32 received a placebo. During withdrawal, patients who switched to the placebo were significantly more likely to lose control of their blood pressure than those who stayed on relacorilant.
Regarding safety, the most common side effects were back pain, acne, joint pain (arthralgia, meaning pain in the joints), bursitis (inflammation of fluid-filled sacs near joints), headache, and insomnia. Importantly, there were no cases of adrenal insufficiency — when the body cannot produce enough cortisol — dangerous potassium lowering, known as hypokalemia, abnormal heart rhythm changes, or uterine lining overgrowth.
Overall, the study showed that relacorilant helped patients maintain better control of their blood pressure and was generally well-tolerated. According to the researchers, these findings suggest that relacorilant is expected to be an effective treatment option for reducing the harmful effects of endogenous Cushing’s syndrome.
