GlaxoSmithKline presents Avandia data to FDA

Philadelphia, PA - The following summarizes GlaxoSmithKline’s [NYSE: GSK] presentation of data on Avandia® (rosiglitazone maleate) to an Advisory Committee of the Food and Drug Administration (FDA)

The GSK presentation demonstrates the weight of scientific evidence available to address a question of increased risk of cardiovascular ischemic events. This question was raised by different meta-analyses performed by GSK, the FDA and one published in the NEJM. Although a meta-analysis can help raise scientific questions for further investigation, such analyses can also have significant limitations. GSK believes a full and scientific evaluation of all the data does not confirm the safety questions originally raised.

Long-term clinical trials — particularly those designed to test a specific outcome in patients with the disease — are the most robust tools available to answer questions raised by meta-analyses. A 1997 published review of meta-analyses revealed 33% of the conclusions of meta-analyses are not confirmed by subsequent clinical trials.

Avandia is the most widely studied oral anti-diabetic medicine for the treatment of type 2 diabetes. The extensive data for Avandia includes:

* 116 clinical trials in over 52,000 patients. These include:
o Three, long-term clinical trials in more than 14,000 patients: ADOPT, DREAM, RECORD, with RECORD specifically studying cardiovascular effects
o A study in a high cardiovascular-risk population: PPAR

* Three epidemiological studies reflecting real life use of diabetes medicines in more than 1.3 million diabetic patients.

Additionally, four other ongoing long-term studies will increase available data on the cardiovascular safety of Avandia: BARI-2D, ACCORD, VADT, APPROACH.

Across the extensive dataset for Avandia, there is no consistent or systematic evidence that Avandia increases the risk of heart attack or cardiovascular death in comparison to other anti-diabetic medicines. Specifically:

* Myocardial ischemia: There was no statistically significant increase in myocardial ischemia in ADOPT, GSK’s long-term comparator study.

* Heart attack: The number of heart attacks across all sources of data is small, the data are inconsistent, and the totality of the evidence does not show a difference between Avandia and the most commonly prescribed anti-diabetic agents. In three epidemiological database studies, the risk of heart attack was similar for Avandia compared to other anti-diabetic agents, and in the one database study comparing Avandia to Actos, there was no difference.

* CV death: The long-term trials provide no evidence of increased CV death or all cause mortality with Avandia compared to the most commonly prescribed oral antidiabetics.

* Stroke: Across the data sources, fewer strokes are observed with Avandia than with other anti-diabetic medicines, although the differences in the long-term trials were not statistically significant.

Importantly, in the ADOPT study, Avandia has been shown to control blood sugar for longer than the commonly used oral anti-diabetic medicines. Avandia is an important treatment option for physicians since diabetes worsens over time, and half of the patients treated today are on combination therapy. Controlling blood sugar has been shown in the UKPDS studies to be important in reducing the risk of serious complications of diabetes, such as blindness, renal problems, amputations and heart attack.

GSK continues to support Avandia as safe and effective when used appropriately.