お知らせ • Jun 09
Corcept Therapeutics Incorporated Presents New Data from Catalyst and Momentum Trials At American Diabetes Association’s 86Th Scientific Sessions
Corcept Therapeutics Incorporated announced the presentation of new data from its CATALYST and MOMENTUM trials at the American Diabetes Association’s 86th Scientific Sessions. In the CATALYST trial, patients with hypercortisolism treated with Korlym exhibited clinically and statistically significant improvements in hemoglobin A1c (HbA1c) and clinically meaningful reductions in body weight, body mass index and waist circumference, with numerically greater benefit in those taking GLP-1 receptor agonists or tirzepatide. The CATALYST trial screened 1,057 patients with difficult-to-control type 2 diabetes (HbA1c of 7.5 – 11.5% despite receiving multiple glucose-lowering medications) and found that 24% had hypercortisolism (cortisol levels of greater than 1.8 µg/dL in the 1 mg dexamethasone suppression test (DST)). In CATALYST’s treatment phase, 136 of the patients who had been found to have hypercortisolism were randomized 2:1 to receive either Korlym or placebo for 24 weeks. Patients who received Korlym exhibited a clinically meaningful and statistically significant reduction in HbA1c (1.3%), and clinically meaningful reductions in body weight, body mass index and waist circumference. The most common adverse events (greater than 10%) were hypokalemia, fatigue, nausea, vomiting, headache, peripheral edema, diarrhea and dizziness. The data presented at ADA described treatment outcomes in the 71 patients in CATALYST who were taking GLP-1 receptor agonists or the GLP-1/GIP agonist tirzepatide. In this group, patients who received Korlym exhibited numerically greater benefit than the overall study population with reductions in HbA1c (1.7%), body weight (6.1 kg), body mass index (2.0 kg/m2) and waist circumference (6.5 cm), compared to patients who received placebo (all nominal p-values less than 0.04). Late-breaking data from the MOMENTUM trial confirm high prevalence of endogenous hypercortisolism in patients with type 2 diabetes and resistant hypertension. At ADA, Corcept also presented late-breaking data from its MOMENTUM trial, which screened 1,086 patients with resistant hypertension (as defined by the American Heart Association’s criteria) and found that 27.3% of them had hypercortisolism. The prevalence of hypercortisolism was even higher in patients who had hemoglobin A1c (HbA1c) of 7.5% or higher and were taking 3 or more blood pressure medicines: 36.6% in CATALYST and 32.6% in MOMENTUM. CATALYST is the largest and most rigorous trial ever conducted to determine the prevalence of hypercortisolism in patients with difficult-to-control type 2 diabetes and assess the effect of treating patients found to have hypercortisolism with a cortisol modulator. The initial prevalence phase of the trial screened 1,057 patients with difficult-to-control type 2 diabetes (i.e., patients with HbA1c greater than 7.5% despite receiving multiple glucose-lowering medications, including best-in-class therapies such as GLP-1 and GLP-1/GIP agonists) at 36 sites in the United States. Based on results from a standard 1-mg dexamethasone suppression test, 24% of the patients screened were found to have hypercortisolism and were eligible to enter the trial’s treatment phase, where they were randomized, 2:1, to receive either Korlym or placebo for 24 weeks. One hundred thirty-six patients enrolled in the treatment phase. MOMENTUM was the largest trial ever conducted to assess the prevalence of hypercortisolism in patients with resistant hypertension. A total of 1,086 patients were screened at 50 sites in the United States. All patients had resistant hypertension as defined by the American Heart Association’s criteria (systolic blood pressure greater or equal to 130 mmHg despite taking 3 or more blood-pressure lowering medications, including a diuretic, or taking 4 or more blood-pressure lowering medications). Using a simple, standardized 1-mg dexamethasone suppression test (DST), 27% of these patients were found to have hypercortisolism. Hypercortisolism, also known as Cushing’s syndrome, is caused by excessive activity of the hormone cortisol. Symptoms vary, but most patients experience one or more of the following manifestations: hypertension, central obesity, elevated blood sugar and difficult-to-control type 2 diabetes, severe fatigue and weak muscles. Irritability, anxiety, depression and cognitive disturbances are common. Hypercortisolism can affect every organ system and can be fatal if not treated effectively. Cardiovascular events are the most common cause of death among patients with hypercortisolism. Recent research shows that endogenous hypercortisolism is more prevalent than previously believed. KORLYM (mifepristone) is a cortisol receptor blocker indicated to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery. Limitations of use: KORLYM should not be used in the treatment of patients with type 2 diabetes unless it is secondary to Cushing’s syndrome. Mifepristone is a potent antagonist of progesterone and cortisol via the progesterone and glucocorticoid (GR-II) receptors, respectively. The antiprogestational effects will result in the termination of pregnancy. Pregnancy must therefore be excluded before the initiation of treatment with Korlym and prevented during treatment and for one month after stopping treatment by the use of a nonhormonal medically acceptable method of contraception unless the patient has had a surgical sterilization, in which case no additional contraception is needed. Pregnancy must also be excluded if treatment is interrupted for more than 14 days in females of reproductive potential. Contraindications include pregnancy; patients taking simvastatin or lovastatin and CYP3A substrates with narrow therapeutic ranges; patients receiving systemic corticosteroids for lifesaving purposes; women with a history of unexplained vaginal bleeding or endometrial hyperplasia with atypia or endometrial carcinoma; patients with known hypersensitivity to mifepristone or to any of the product components. Adrenal insufficiency: Patients should be closely monitored for signs and symptoms of adrenal insufficiency. Hypokalemia should be corrected prior to treatment and monitored for during treatment. Measure serum potassium 1-2 weeks after starting or increasing the Korlym dose, and periodically thereafter. Mifepristone-induced hypokalemia should be treated with potassium supplementation based on severity. If hypokalemia persists despite potassium supplementation, consider adding mineralocorticoid antagonists. Vaginal bleeding and endometrial changes: Women may experience endometrial thickening or unexpected vaginal bleeding. Use with caution if the patient also has a hemorrhagic disorder or is on anticoagulant therapy.