Corcept Therapeutics announced positive results from the treatment phase of the CATALYST trial, a Phase 4 study evaluating mifepristone (Korlym) in patients with hypercortisolism (Cushing’s syndrome) and difficult-to-control type 2 diabetes (T2D). The trial met its primary endpoint, demonstrating a clinically meaningful and statistically significant improvement in hemoglobin A1c (HbA1c) levels.
The CATALYST trial enrolled 1057 patients across 36 sites in the US. The first part of the trial assessed the prevalence of hypercortisolism in patients with difficult-to-control T2D, defined as HbA1c ≥7.5% despite optimal therapies, including GLP-1 agonists. The treatment phase involved 136 patients randomized 2:1 to receive mifepristone or placebo for 24 weeks.
Key Findings from the CATALYST Trial
The primary endpoint of the treatment phase was the reduction in HbA1c levels. Patients treated with mifepristone experienced a significant decrease from baseline of 1.47%, compared to a 0.15% decrease in the placebo group (placebo-adjusted reduction, 1.32%; P < .0001). The safety profile of mifepristone remained consistent with its established label, with no new safety signals or adverse events observed.
"CATALYST’s first part showed that hypercortisolism is much more common than previously assumed," said investigator Ralph DeFronzo, MD, chief of the Diabetes Division and professor of medicine at UT Health San Antonio. "The results announced today show that [mifepristone] is a safe and effective treatment option. Reductions in HbA1c of this magnitude are of great clinical benefit."
Hypercortisolism and Type 2 Diabetes
Hypercortisolism, caused by excessive cortisol activity, can lead to hypertension, central obesity, elevated blood sugar, and difficult-to-control T2D. It can affect multiple organ systems and can be lethal if untreated. Mifepristone, a cortisol receptor blocker, is indicated for controlling hyperglycemia secondary to hypercortisolism in adults with endogenous hypercortisolism who have T2D or glucose intolerance and have failed surgery or are not surgical candidates.
The first part of the CATALYST trial revealed that approximately 1 in 4 patients with difficult-to-control T2D exhibit endogenous hypercortisolism. Specifically, 23.8% of patients screened were eligible for the treatment phase, highlighting the prevalence of undiagnosed hypercortisolism in this population.
Implications for Clinical Practice
The results of the CATALYST trial suggest that screening for hypercortisolism should be expanded in patients with difficult-to-control T2D. The significant reduction in HbA1c with mifepristone indicates a potential for improved glycemic control and better health outcomes in this patient population. Complete results from CATALYST will be presented at a medical conference next year.
"They are particularly compelling, given that the patients in CATALYST have been receiving our best therapy – but continued to experience serious disease," DeFronzo added. "These findings should prompt expanded screening for hypercortisolism, more effective treatment, and better health outcomes for patients who are struggling today."
