July 12 (Bloomberg) -- Takeda Pharmaceutical Co.'s Actos diabetes pill may not have the heart-attack risk linked to GlaxoSmithKline Plc's similar drug, Avandia.

An analysis of Takeda studies, scheduled for completion this month, may show Actos is free of the cardiac side effect and could catapult the Takeda drug past Avandia as the world's best- selling oral diabetes medicine, analysts say. A report by the Cleveland Clinic in May said Avandia may increase the chances of heart attacks by 43 percent.

The U.S. Food and Drug Administration will hold a hearing July 30 to review the Avandia heart attack connection. The FDA hasn't required Takeda to testify, suggesting the agency's concern is limited to Avandia, said Robert Spanheimer, a Takeda executive. He cited a study called Proactive that found Actos protects against blood clots that cause heart attacks. A pending review of past studies, a process known as meta analysis, may confirm the finding, he said.

``I think Proactive is an accurate signal'' of the difference between Actos and Avandia, said Spanheimer, Takeda's senior medical director for diabetes, in an interview. ``We are actually in the process of putting that meta analysis together and hope to have it submitted to the FDA before the advisory meeting.''

Proactive, a study of 5,000 diabetics released in 2005, found Actos reduced the risk of heart attacks, strokes and death by 16 percent. The researchers followed patients from 19 European countries for at least 2.5 years.

Drugs Differ

There are differences between the drugs as Actos lowers bad cholesterol while Avandia raises it, said Howard Weintraub, director of the center for prevention of cardiovascular disease at New York University Medical Center, in an interview.

``From the data I have available, I believe there is no risk for Actos to cause heart attacks and if anything I believe it's beneficial for preventing them,'' Weintraub said. ``In the studies of Actos, every one I've seen, there is no signal at all of an increased risk for heart attacks. With Avandia, we have the exact opposite.''

Actos generated $2.77 billion last year, making it the No. 2 oral diabetes drug behind Avandia, with $3.3 billion in 2006 sales. An FDA finding that heart attack risks are confined to Avandia may help Takeda cement Actos as the world's best-selling diabetes pill.

Best-Selling Drug

``It's an opportunity to go from being No. 2 to No. 1,'' said Ira Loss, an analyst with Washington Analysis that has closely monitored the FDA for more than two decades.

Glaxo considers the best way to identify cardiovascular risk is with long-term clinical trials, not with meta analyses, said Mary Anne Rhyne, a spokeswoman for the London-based drugmaker.

``It would be especially difficult to make meaningful, scientifically valid comparisons between two meta analyses that look at different products and very different collections of data,'' she said.

FDA spokeswoman Susan Cruzan declined to comment on the July 30 hearing.

Actos use accelerated after the Avandia warnings, climbing 14 percent to 251,000 U.S. prescriptions for the week of July 6, according to Verispan LLC in Yardley, Pennsylvania, which tracks pharmaceutical data. Actos is capturing more than 70 percent of all new prescriptions for insulin-sensitizing drugs, up from about half before the Avandia study was published.

Shares Decline

Takeda shares rose 40 yen, or a half percent, to 7,990 yen on the Tokyo Stock Exchange, paring their decline this year to 2.2 percent. Glaxo shares rose 17 pence, or 1.3 percent, to 1282 pence at 2:44 p.m. in London, and have fallen 5.9 percent this year before today.

Avandia and Actos belong to a family of medicines known as thiazolidinediones, or TZDs. They work by making diabetics more sensitive to the hormone insulin and have been taken by more than 15 million patients since they became available in 1999.

The introduction of competing treatments, including Merck & Co.'s Januvia and Byetta, an injected drug from Amylin Pharmaceuticals Inc. and Eli Lilly & Co., may slow their growth. Confining the heart attack link to Avandia may fuel a surge in sales of Actos, which accounted for one-quarter of Osaka-based Takeda's revenue last year.

``We think gains in Actos' market share are likely'' after the FDA review, said Hidemaru Yamaguchi, an analyst at Nikko Citigroup in Tokyo. He raised his rating on Takeda to ``buy'' from ``hold'' after Avandia's heart risks were publicized.

An interim analysis of Glaxo's largest study, known as Record, found patients taking Avandia weren't more likely to be hospitalized or die from cardiovascular causes. The research is still under way and doctors said the results aren't definitive.

Heart Attacks

At the FDA's request, Takeda is compiling findings from its past studies on Actos in a meta analysis to look for any signs that the drug poses heart attack risks. Spanheimer said he hasn't seen the results of the review, though he expects it will confirm the Proactive findings.

The May 21 Avandia study published in the New England Journal of Medicine was also a meta analysis. It was done by Steven Nissen, the head of cardiology at the Cleveland Clinic in Ohio, and Kathy Wolski, a statistician there. They analyzed data from 42 trials and found a 43 percent increased risk of heart attacks. A similar review conducted by Glaxo and submitted in preliminary form to regulators in 2005 suggested a 30 percent increased risk of cardiovascular complications.

Other Complications

Actos and Avandia both cause other complications, most notably heart failure that can develop twice as often in diabetics taking either pill. If caught early, doctors can treat the condition, Spanheimer said, making quick detection critical.

Heart failure develops when a weakened and enlarged heart doesn't pump oxygen-rich blood efficiently. Patients with milder cases may experience fatigue and need to limit their physical activity. In the most severe cases, heart failure can cause fluid to build up in the lungs and eventually kill.

While that information about heart failure is already included in the labels for both medications, the FDA has asked Takeda and Glaxo to strengthen their warnings. Some doctors and patients are confusing heart failure and heart attacks, a condition that permanently kills cardiac muscle, Spanheimer said.

To contact the reporters on this story: Michelle Fay Cortez at mcortez@bloomberg.net; Lisa Rapaport in New York at Lrapaport1@bloomberg.net

Last Updated: July 12, 2007 09:47 EDT