FDA Approves New, Once-A-Day COREG CR For The Treatment Of Three Key Cardiovascular Conditions

GlaxoSmithKline (NYSE: GSK) and Flamel Technologies (NASDAQ:FLML) today announced FDA approval of once-a-day Coreg CR (carvedilol phosphate) extended-release capsules, for the treatment of three cardiovascular conditions:

• -- High blood pressure, also known as hypertension.
• -- A heart attack that has reduced how well the heart pumps (known medically as post-myocardial infarction left ventricular dysfunction).
• -- Mild to severe heart failure.

COREG CR will utilize Flamel's proprietary Micropump technology, which controls the delivery of carvedilol helping to maintain appropriate amounts of medicine in the body over a 24-hour span. This technology allows COREG CR to be dosed once daily, in contrast to immediate-release COREG (carvedilol) tablets, which patients must take twice daily. GlaxoSmithKline plans to begin shipping COREG CR in the first quarter of 2007.

"Once-a-day COREG CR will simplify the treatment regimen and offer the potential for improved compliance for patients with heart disease," said Michael A. Weber, M.D., professor of medicine, at the SUNY Downstate Medical College of Medicine, Brooklyn, New York. "The combination of this benefit with the proven effectiveness of COREG offers a treatment advantage for the growing number of heart patients who take multiple medications every day."

COREG CR is a third generation "beta blocker," which is a class of medicines that work by slowing heart rate and lowering the force with which it pumps. Studies of COREG CR indicate it is generally well tolerated with a low incidence of adverse events. COREG CR, a once-a-day medicine, is approved to treat the same conditions as twice-a-day COREG, which has established a significant role in the treatment of heart disease.

Evidence of the treatment benefits of COREG has come from multiple clinical studies. These COREG studies include COMET, published in 2003. This trial of more than 3,000 heart failure patients demonstrated that patients receiving COREG lived 1.4 years longer compared to patients taking the beta blocker metoprolol tartrate.

Important insights into the effect of COREG following a heart attack came from the CAPRICORN trial, published in 2001. This study showed that when COREG was maintained long term in patients following a heart attack that reduced how well the heart pumps, the risk of dying was reduced by 23 percent. In addition, patients taking COREG had a significantly reduced risk of having another heart attack.

Another study, GEMINI, in 2004, evaluated patients with hypertension and underlying diabetes. Older beta blockers have generally been regarded as having a negative impact on key metabolic parameters. In contrast, the GEMINI study results showed that COREG effectively lowered blood pressure while having a neutral impact on blood-sugar levels, lipids and weight gain.

Heart Disease and the Role of Beta Blockers

Heart disease is the leading cause of death in the United States. The American Heart Association estimates that 71.3 million people in America have heart disease. Beta blockers are a critical component of the treatment regimen for many patients with high blood pressure, those who have had heart attacks and those with heart failure.

The use of newer beta-blockers like COREG is supported by current evidence-based guidelines, such as the AmericanCollegeof Cardiology and American Heart Association (ACC/AHA) Heart Failure Guidelines and the American Association of Clinical Endocrinologists (AACE) Hypertension Task Force's Medical Guidelines for Clinical Practice for the Diagnosis and Treatment of Hypertension.

COREG CR Dose Strengths

COREG CR will be available in four dosage strengths: 10 mg, 20 mg, 40 mg and 80 mg.

Important COREG CR Safety Information

It is important for patients to take their medicine every day as directed by their doctors or health care providers. Patients taking COREG CR should avoid stopping therapy abruptly. With certain beta-blocking agents, stopping therapy abruptly has led to chest pain and, in some cases, heart attack. If their doctor decides that they should stop taking COREG CR, their doctor or health care provider may slowly reduce their doses over a period of time before stopping it completely.

Some common side effects associated with COREG CR include shortness of breath, a slow heartbeat, weight gain, fatigue, hypotension, dizziness or faintness. People taking COREG CR who have any of these symptoms should call their doctor. Additionally, if patients experience fatigue or dizziness, they should sit or lie down and avoid driving or hazardous tasks. Beta-blockers may mask the symptoms of low blood sugar or alter blood sugar levels. People with diabetes should report any changes in blood sugar levels to their physician. Contact lens wearers may produce fewer tears or have dry eyes. As with any medicine, patients taking COREG CR should first tell their doctor what other medications they are taking.

As with any medicine, there are some people who should not take COREG CR. The people who should not take COREG CR include those with severe heart failure who are hospitalized in the intensive care unit. Also, people who require certain intravenous medications that help support their circulation (inotropic medications) should not receive COREG CR. Other people who should not take COREG CR are those who are prone to asthma or other breathing problems, those with a very slow heartbeat or heart that skips a beat (irregular heartbeat) and those with liver problems.

About Flamel Technologies

Flamel Technologies, S.A.is a biopharmaceutical company principally engaged in the development of two unique polymer-based delivery technologies for medical applications. Flamel's Medusa technology is designed to deliver controlled-release formulations of therapeutic proteins and peptides. Micropump is a controlled release and taste-masking technology for the oral administration of small molecule drugs.

About GlaxoSmithKline

GlaxoSmithKline, one of the world's leading research-based pharmaceutical and health care companies, is committed to improving the quality of human life by enabling people to do more, feel better and live longer.