Takeda responds to FDA recommendation on Actos

ttp://www.tgrd.comJul 30 2007

Following a joint meeting today of the U.S. Food and Drug Administration (FDA) Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee, Takeda Global Research & Development (TGRD) underscores its position that ACTOS(R) (pioglitazone HCl) offers a proven safety profile regarding the risk of cardiovascular disease.

"The breadth and depth of ACTOS data - encompassing more than 16,000 patients over the past 10 years - is consistent: Short- and long-term studies, both prospective and observational, studies in both humans and animals, all have shown no evidence that ACTOS is associated with an increased risk of heart attack or stroke," said Mehmood Khan, M.D., TGRD president. "Critical in this body of data is the PROactive (PROspective PioglitAzone Clinical Trial In MacroVascular Events) study, since the only scientific way to determine a medication's safety is a prospective, long-term trial."

PROactive was a prospective, randomized, placebo-controlled outcomes trial. The PROactive study included 5,238 patients with type 2 diabetes and a history of macrovascular disease, who were force titrated up to 45 mg daily of either ACTOS or placebo. In this study, there was no difference in the number of macrovascular events between standard of care and ACTOS, and standard of care alone. Although there was no statistically significant difference between ACTOS and standard of care for the primary endpoint, there was no increase in mortality or total macrovascular events with ACTOS.

The ACTOS Prescribing Information was recently revised by the FDA to include this reassuring cardiovascular safety data. ACTOS is the only thiazolidinedione (TZD) with safety data from a cardiovascular outcomes trial in its label.

"Although drugs may be in the same class, they also can have different clinical effects due to differences in molecular structure," said Dr. Khan. "ACTOS is an effective and appropriate treatment option for people with type 2 diabetes. Since the introduction of ACTOS in August 1999, almost 70 million prescriptions have been written, covering more than 8 million patients and 4.5 million patient years."

Takeda has consistently emphasized the importance of physician education and patient safety in all communications involving ACTOS and has prioritized communicating the appropriate use of ACTOS in patients with type 2 diabetes.

Advisory Committee meetings are discussions of pending applications and other public health matters. The FDA frequently convenes its panel of outside experts to provide guidance and recommendations; however, the agency is not bound to follow the recommendations. This joint committee meeting reviewed the cardiovascular ischemic/thrombotic risks of the thiazolidinediones, with focus on rosiglitazone, as presented by FDA and GlaxoSmithKline.

ACTOS works by directly targeting insulin resistance, a condition in which the body does not efficiently use the insulin it produces to control blood glucose levels. ACTOS is taken once daily as an adjunct to diet and exercise, and is approved for use for type 2 diabetes as monotherapy to lower blood glucose and in combination therapy with insulin, sulfonylureas or metformin.

ACTOS is not for everyone. ACTOS can cause fluid retention that may lead to or worsen heart failure, so tell your doctor if you have a history of these conditions. Talk to your doctor immediately if you experience rapid weight gain, fluid retention, or shortness of breath while taking ACTOS. If you have moderate to severe heart failure, ACTOS is not recommended. Your doctor should perform a blood test to check for liver problems before you start ACTOS and periodically thereafter.

Do not take ACTOS if you have active liver disease. Talk to your doctor immediately if you experience nausea, vomiting, stomach pain, tiredness, loss of appetite, dark urine, or yellowing of the skin. If you are of childbearing age, talk to your doctor before taking ACTOS as it could increase your chance of becoming pregnant. Some people taking ACTOS may experience flu-like symptoms, mild to moderate swelling of legs and ankles, and anemia. When taking ACTOS with insulin or sulfonylureas, you may be at risk for low blood sugar. Patients with diabetes should have regular eye exams. If you experience vision problems, consult your doctor immediately. Very rarely, some patients have experienced visual changes while taking ACTOS.