Glaxo's HIV Drug Ziagen Tied to Heart Ills in Review (Update1)

Aug. 7 (Bloomberg) -- GlaxoSmithKline Plc's HIV drug Ziagen was linked in a second study to an increased risk of heart attacks, especially for older patients, scientists said today.

Patients taking combinations of HIV drugs who were treated with abacavir, an active ingredient in Glaxo's Ziagen and Epzicom, were almost twice as likely to have heart attacks as those getting alternative treatments, said Jens Lundgren, a researcher at the University of Copenhagen. His team had found the same risk in a previous study released in February.

The drugs were most likely to raise the danger of heart attacks in older patients who began the study with signs of blood vessel damage or other characteristics that might make them vulnerable to heart disease, Lundgren said. As more HIV patients live to advanced ages, doctors may want to consider the effect on heart disease in choosing drugs, he said.

``In older patients with several risk factors for heart disease, this is something, at least from our data, that we have to pay attention to,'' Lundgren said in an interview at the International AIDS conference in Mexico City, where the results were presented. ``In younger populations without cardiovascular risk this is not a public health concern.''

Ziagen's sales were $218 million worldwide in 2007, with $89 million in the U.S., according to Glaxo. Epzicom's sales were $648 million, with $284 million in the U.S.

American depositary receipts of London-based Glaxo fell 92 cents, or 1.9 percent, to $48.11 at 4:02 p.m. in New York Stock Exchange composite trading. One receipt equals two ordinary shares.

Earlier Study

Earlier, Lundgren and his colleagues in the Data Collection on Adverse Events of Anti-HIV Drugs Study Group, or DAD, analyzed studies that involved 33,000 patients. That analysis published in February found a link between abacavir and heart attacks.

``We wanted to see if the findings from DAD were something consistent and can be observed in other databases,'' Lundgren said.

So the group analyzed results from the Strategies for Management of Antiretroviral Therapy, or SMART trial, a study in 2006 that followed 5,472 HIV patients for an average of 16 months, looking for signs of heart, kidney or liver disease.

The results were almost identical to the earlier study, Lundgren said.

Glaxo didn't see the same effect in an analysis of 54 earlier company studies of about 14,600 people taking either abacavir or alternatives, said John Pottage, Glaxo's vice president for global clinical development. Those trials weren't designed to look for effects in the heart, he said in an interview at the Mexico City conference.

Caution Added

Glaxo added a caution to Ziagen's prescribing information last month, citing results from the DAD study, which the company called ``inconclusive.'' Patients taking the drug should be counseled to lower blood pressure and cholesterol, quit smoking, and manage diabetes if they have it, according to the revised label.

``We want to pay attention to reversible risk factors and get people to modify those,'' Pottage said. ``That's the first task.''

At least 90 percent of HIV patients aren't at high risk of heart disease, and might not be affected by any theoretical risk from the drug, Pottage said.

A study of thousands of patients lasting a few years would be needed to prove the heart disease link to the drug, according to Pottage and Lundgren. Such as study might cost as much as $50 million, Lundgren said.

`Patients Are Aging'

``The problem is that patients are aging,'' he said. ``You could wait 10 years until more patients are 55 and at risk of heart disease, or do more studies of this while the events are relatively rare and find out what's going on.''

Abacavir can also cause rare, strong allergic reactions in some patients, and Glaxo cautions that patients should be tested for a gene marker linked to the reactions before taking Ziagen or Epzicom.

The extra risk of heart disease that Lundgren found in his studies disappeared almost as soon as people stopped taking Ziagen and Epzicom. The drug may contribute to rare events, such as the breakup of clots on blood vessel walls, which can lead to heart attacks, he said.

The SMART trial analysis is ``compelling,'' said Anton Pozniak, an HIV consultant physician at Chelsea and Westminster Hospital, London.

``When our patients who are on it have high cardiovascular risk, we have a discussion with them about it,'' he said in an interview at the AIDS conference. ``If there are no alternatives available to them, they may have to stay on it.''

To contact the reporter on this story: John Lauerman in Boston at jlauerman@bloomberg.net.

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net.