The FINANCIAL — Takeda Pharmaceuticals U.S.A. Inc. and Takeda Pharmaceutical Company Limited (“Takeda”) on April 15 announced that members of the Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) of the United States (U.S.) Food and Drug Administration (FDA) convened to review one of the first cardiovascular (CV) outcomes trials (CVOT) in patients with Type 2 diabetes, EXAMINE (EXamination of CArdiovascular OutcoMes: AlogliptIN vs. Standard of CarE in Patients with Type 2 Diabetes Mellitus and Acute Coronary Syndrome).
The Committee voted that, based on the data presented, the results of EXAMINE demonstrate that the use of alogliptin in patients with Type 2 diabetes has an acceptable CV risk profile. All 16 voting members of the Committee supported this recommendation. In addition, 13 out of 16 Committee members voted that safety information from the EXAMINE study should be added to the alogliptin labeling and the other three members voted for no change to the labeling, according to Takeda.
“Patients with diabetes are at an increased risk of cardiac related comorbidities such as heart disease and stroke, as well as hospitalized heart failure and cardiac death,” said William B. White, MD, Professor, Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, Connecticut, U.S., on behalf of the EXAMINE Steering Committee and Investigators. “Today’s Advisory Committee recommendation provides important information about alogliptin that may be useful for prescribing physicians as they consider appropriate treatment options for patients with Type 2 diabetes.”
EXAMINE, a large, randomized, double-blind, placebo-controlled outcomes study, was completed as a result of the U.S. FDA 2008 Guidance, titled “Guidance for Industry: Diabetes Mellitus – Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes,” for all Type 2 diabetes treatments under development since the issuance of the guidance. The EXAMINE trial was designed to evaluate CV safety following treatment with alogliptin in addition to standard of care, versus placebo in addition to standard of care, in patients with Type 2 diabetes who were at high risk for major adverse cardiovascular events (MACE) due to recent acute coronary syndrome (ACS). The trial’s primary objective was to evaluate non-inferiority of CV risk based on a primary composite endpoint of CV death, nonfatal myocardial infarction (MI) and nonfatal stroke.
“Takeda is pleased with the recommendation of the Committee and we remain confident in alogliptin as an important treatment option for patients living with Type 2 diabetes,” said Robert Jackson, MD, MBA, Vice President, Global Medical Head, CVM-Respiratory Therapy, Takeda Pharmaceuticals International.
“Today’s outcome reinforces that the global EXAMINE trial met the FDA postmarketing guidance requirements. The trial is important as it assesses cardiovascular safety in patients known to be at a high risk for cardiovascular disease.”
Patient safety is a top priority for Takeda, and we remain committed to ongoing clinical research to understand and investigate potential safety concerns. Alogliptin has been studied as a monotherapy and in combination with metformin, a sulfonylurea (SU), a thiazolidinedione (TZD), and insulin in a comprehensive global clinical program comprising more than 50 clinical studies involving approximately 1,000 healthy adult patients and more than 17,000 adult patients with Type 2 diabetes.
The FDA also asked the Committee to discuss whether additional alogliptin studies are needed and to make any recommendations regarding the evaluation of the risk-benefit profile for alogliptin. In addition to discussing EXAMINE’s pre-specified primary CV outcome data, the Committee discussed other study analyses including heart failure, study data by geographic region, and other data including renal safety findings.
The outcome of the Advisory Committee meeting is non-binding and will be taken into consideration by the FDA.
Alogliptin is the first dipeptidyl peptidase-4 inhibitors (DPP-4i) to report out results on CV safety outcomes in Type 2 diabetes patients who are at high risk due to recent ACS. Heart disease, or cardiovascular disease (CVD), is a commonly occurring comorbid condition in patients living with Type 2 diabetes.
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