Amid Avandia doubts, diabetics consider alternatives

Posted: June 13, 2007

Like many diabetics, pharmacist Ben Briggs was eager to see his blood sugar drop when he began taking his new medicine.

But within two weeks, his ankles started swelling. His weight surged eight pounds, and he felt short of breath. "I was feeling awful," said Briggs, who runs the Lionville Natural Pharmacy & Health Food Store in Chester County. The symptoms stopped after he went off the drug, he said.

Briggs wasn't taking Avandia, the GlaxoSmithKline drug caught in a media firestorm in recent weeks because of its alleged links to higher heart-attack risk. The 59-year-old diabetic was trying Januvia, a competing pill from Merck & Co. Inc. that has benefited mightily from Avandia's problems. Many doctors are switching patients to other drugs, including Januvia, after a prominent researcher challenged Avandia's safety in the May 21 issue of the New England Journal of Medicine.

Yet, as Briggs' experience shows, patients and investors may need to tread carefully. Even newer than Avandia, Januvia has been on the market for only eight months, and prominent critics are already questioning why patients should take it when more proven choices, such as metformin and insulin, are available.

Experts say the questions swirling around diabetes drugs underscore a greater weakness in the drug-approval system. Many diabetes drugs are approved for improving a dimension of care, such as lowering blood sugar. But no one knows whether many of those new drugs can go further and help prevent the bad outcomes that really matter: heart attack, stroke, blindness, and amputation. Proving that can take years and add hundreds of millions of dollars to a drug's development.

Merck, based in Whitehouse Station, N.J., is pressing ahead to broaden the testing of Januvia and to monitor any side effects. The firm has seen no evidence of more heart or ankle-swelling problems in patients taking Januvia than in those not taking the pill, said John Amatruda, Merck's vice president of clinical research for metabolic disorders.

Merck has seen an uptick in nasal inflammation, he said, "but these events are, for the most part, transient." He noted that other diabetes drugs had many side effects and called Januvia "a major advance."

With Avandia under fire, at least some doctors are being cautious, noting that a drug's safety profile can take years to emerge. About 8 percent of new drugs got slapped with major "black box" warnings, and nearly 3 percent were withdrawn, according to a 2002 study in the Journal of the American Medical Association.

That's why Arthur Chernoff, medical director of Albert Einstein Medical Center's Gutman Diabetes Institute, advocates a cautious strategy for new drugs. "I usually hang back and wait for the side effects to occur," he said, "unless there's a compelling need."

Chernoff, who hasn't used Januvia as a first-line drug, said he had seen ankle-swelling in two patients put on Januvia by other doctors. But he said he lacked enough information to know whether the problem was serious or widespread.

James A. Underberg, an assistant professor at the New York University School of Medicine, helped test Januvia and greeted it with enthusiasm when it was approved in October. Now he's more skeptical, noting that the testing focused on blood sugar.

"Does Januvia have an effect on cardiovascular? I have no idea," he said this week. "Doctors have to be concerned about the safety of any new drug."

Patients with Type 2 diabetes, the most common form, don't produce enough of a hormone called insulin, or cannot use what they make. The condition afflicts about 21 million people in the United States - 7 percent of the population - and could strike one in three Americans born in 2000, according to the American Diabetes Association.

For now, Januvia and Merck are riding high. Januvia could gain $300 million a year in sales from Avandia's problems, Deutsche Bank analyst Barbara Ryan said, citing an analysis of doctors' prescribing habits by Mount Laurel-based ImpactRx. Ryan's firm put out a buy recommendation June 5 on Merck stock, citing its cost-cutting and likely sales increases.

Actos, a chemical cousin of Avandia, could benefit even more than Januvia, Ryan said, though it remains unclear whether the problems that appear to bedevil Avandia will apply to Actos, made by Takeda Pharmaceutical Co. Ltd.

David M. Nathan, an endocrinologist at the Harvard Medical School, isn't prescribing Januvia much. He pointed out that Januvia represents the ninth class of diabetes drugs and is the first of its type, called DPP-4 inhibitors, to be approved. The drug raises levels of a natural protein, GLP-1, which induces the pancreas to make insulin and encourages the liver to pump out less glucose.

Januvia is relatively weak at lowering blood sugar and is expensive, Nathan said. Independence Blue Cross will not pay for a Januvia prescription without a pre-authorization review, because it's a new drug, a spokeswoman said. Members who get turned down have to pay about $170 a month at one suburban pharmacy.

Januvia was marketed for its safety, but "really, how safe is it?" asked Daniel Hoffman, president of Pharmaceutical Business Research Associates, a consulting firm in Glenmoore, Chester County. "I would really like to see some well-designed studies to see who would benefit the most from this drug."


 

Q&A today: Arthur Chernoff of the Albert Einstein Medical Center will answer questions online on the problems surrounding Avandia and other diabetes drugs, starting at 10 a.m. at


Contact staff writer Karl Stark

at 215-854-5363 or kstark@phillynews.com.

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