NEWS OF THE WEEK
DIABETES DRUG COMES UNDER FIRE The diabetes drug Avandia has been linked to increased risk of heart attacks.
PHARMACEUTICALS: Safety questions about GSK's Avandia may drive patients to alternative treatments
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PAPER in the New England Journal ofMedicine is questioning the safety of GlaxoSmithKline's multi-billion-dollar diabetes drug Avandia and could have a ripple effect on an entire range of type 2 diabetes treatments (DOI: io.i056/NEJMoao7276i). The report presents findings from Steven Nissen, the Cleveland Clinic cardiologist who first raised concerns about the safety of the Merck & Co. painkiller Vioxx. Nissen analyzed combined data from 42 previous clinical trials of Avandia, all of which were available on a GSK website, and found that patients taking Avandia were about 43% more likely to have a heart attack than those who weren't. He claims that the increased risk of dying from cardiovascular causes when taking the drug is "statistically significant."
CAR MAKERS VERSUS CALIFORNIA GLOBAL WARMING: Adversaries prepare for fight over limits on vehicle emissions
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ALIFORNIA and automakers are gearing up for a major court battle over the regulation of greenhouse gas emissions from vehicles. Both sides are waiting for EPA to decide whether it will allow California to place a limit on greenhouse gas emissions from new cars and trucks, beginning in model year 2009. Whatever it decides, the agency is likely to end up in court. EPA is considering California's request in the wake of a Supreme Court ruling in April that carbon dioxide is an air pollutant (C&EN, April 9, page 9). The agency is expected to announce its decision on California's request this summer. At an EPA public meeting and a Senate hearing, both held on May 22, California Attorney General Edmund G. (Jerry) Brown Jr. argued that the Golden State WWW.CEN-0NLINE.ORG
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GSK says it "strongly disagrees with the conclusions" of the NEJM article, citing conflicting safetyresults from different trials. Last year, the company notified FDA of cardiovascular incidents in one trial and added a related warning to the drug's label. With $3 billion in sales in 2006, Avandia is GSK's second-best selling drug and a critical component of its portfolio. The full impact of the NEJM study remains to be seen, but analysts believe doctors will start switching patients to other treatments, particularly those with a mechanism of action different from that of Avandia. Avandia works by acting on the peroxisome proliferator-activated receptor (PPAR), a drug target that has caused safety concerns in the past. In 2005, Merck and Bristol-Myers Squibb withdrew a New Drug Application for their PPAR agonist Pargluva after FDA asked for a five-year cardiovascular safety study. And Warner-Lambert pulled the drug Rezulin from the market in 2000 after it was shown to cause liver toxicity. FDA is now looking at the safety of Takeda Pharmaceutical's Actos, introduced in 1999, though large-scale studies suggest the drug doesn't have the same impact on heart health. Morgan Stanley drug analyst Jami Rubin believes the lion's share of diverted Avandia prescriptions will go to Merck's Januvia and Amylin's Byetta, both of which act on a pathway of glucagenlike peptide-i, a gastrointestinal hormone. Rubin sees Merck's Januvia franchise winning anywhere from 30 to 60% of lost Avandia sales by 2010.—LISA JARVIS
should get federal approval for regulating vehicles' greenhouse gas emissions. Global warming has reduced snow pack, raised sea levels, increased urban ozone pollution, and boosted the risk of wildfires in California, Brown said. Regulating greenhouse gas emissions from vehicles is an essential component of addressing climate change, he added. But the auto industry contends that EPA should reject the request because the state's emission control plan for vehicles won't, by itself, remedy the impacts of climate change. Steven Douglas, director of environmental affairs for the Alliance of Automobile Manufacturers, said at the EPA meeting that California has not demonstrated how the vehicle emission control plan will alleviate sea-level rise or other effects of global warming. The Clean Air Act allows California to set tighterthan-federal standards for vehicle emissions to address environmental problems only within the state, Jonathan H. Adler, a law professor at Case Western Reserve University, told the Senate Environment & Public Works Committee. Because climate change is a global problem, the agency's decision "could be subject to court challenge" if EPA grants the California request, Adler said. Meanwhile, Brown said California is ready to sue if EPA rejects the request or fails to make its decision by Oct. 24, a deadline established by Gov. Arnold Schwarzenegger.—CHERYL HOGUE
MAY 28, 2007
