Korlym reduces blood sugar in Cushing’s patients with diabetes
Trial data show significant reduction in type 2 diabetics' hemoglobin A1c
Korlym (mifepristone) significantly reduced levels of hemoglobin A1c, a marker that reflects blood sugar levels over the previous months, in people with Cushing’s syndrome and difficult-to-control type 2 diabetes.
That’s according to new data from a Phase 4 clinical trial, CATALYST (NCT05772169), which screened 1,057 patients with difficult-to-control high blood sugar levels. A quarter of them also had high cortisol levels (hypercortisolism), the hallmark of Cushing’s. Complete results from CATALYST will be presented at a medical conference next year, according to Corcept Therapeutics, the company marketing Korlym,
“The results of the CATALYST study will enable physicians to more accurately diagnose and treat patients with hypercortisolism — a serious and deadly disease,” Bill Guyer, Corcept’s chief development officer, said in a company press release. “One in four patients with difficult-to-control type 2 diabetes have hypercortisolism and Korlym, a cortisol modulator, was highly effective in controlling hyperglycemia [high blood sugar] in this patient population.”
Cushing’s syndrome refers to conditions driven by high levels of the hormone cortisol. Cushing’s disease, one of its most common forms, is caused by a tumor in the brain’s pituitary gland that produces large amounts of adrenocorticotropic hormone, a signaling molecule that triggers excessive cortisol production.
Cortisol has many functions in the body, including helping regulate blood sugar, or glucose, levels. High cortisol levels may cause blood sugar levels to rise, which may lead to glucose intolerance and type 2 diabetes. High blood sugar levels and diabetes are both common complications of Cushing’s.
Binding to receptors
Korlym is an oral therapy that works by binding to glucocorticoid receptors — those to which cortisol normally binds to exert its effects — blocking cortisol’s access to them and ultimately preventing blood sugar levels from rising. It is approved to control high blood sugar levels in adults with Cushing’s syndrome who have glucose intolerance or type 2 diabetes, and for whom surgery was ineffective or not an option.
CATALYST is a two-part trial that enrolled patients at more than 30 sites in the U.S. In the first part, 1,057 participants with difficult-to-treat type 2 diabetes, defined as hemoglobin A1c greater than 7.5% despite optimal treatment, were screened for hypercortisolism. Results indicated that 23.8% of the participants had hypercortisolism.
“CATALYST’s first part showed that hypercortisolism is much more common than previously assumed,” said Ralph DeFronzo, MD, professor of medicine at UT Health San Antonio and a CATALYST study investigator.
From this group of patients, 136 were randomly assigned to receive Korlym or a placebo for about six months in the study’s second part.
The trial met its main goal of significantly reducing hemoglobin A1c, with Korlym-treated patients having a decrease of 1.47% from the trial’s start, compared with a 0.15% reduction in the placebo group.
“Reductions in hemoglobin A1c of this magnitude are of great clinical benefit,” said DeFronzo. “They are particularly compelling, given that the patients in CATALYST had been receiving our best therapies — but continued to experience serious disease. These findings should prompt expanded screening for hypercortisolism, more effective treatment and better health outcomes for patients who are struggling today.”
Korlym’s safety profile was consistent with the medication’s label, with no new adverse events identified, the company said.
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