Has Merck Learned Anything from Vioxx and Vytorin?
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Even as Merck seeks closure on its Vioxx nightmare by paying $4.85 billion to tens of thousands of plaintiffs who took the painkiller -- not that it did anything wrong -- the bad ink continues.
Articles about Vioxx -- withdrawn from the market in 2004 for doubling stroke and heart attack risk -- in the April 16, 2008, edition of JAMA charge that Merck disguised mortality data it submitted from Vioxx trials to the FDA and wrote the scientific papers itself that it claimed were penned by doctors.
Merck transposed its own clinical study results of 34 deaths in the Vioxx group and 12 in the placebo group to 29 deaths in the Vioxx group and 17 in the placebo group when it submitted data to the FDA, write Bruce Psaty, MD, PhD; and Richard Kronmal, PhD, professors at the University of Washington, in JAMA. Worse, Merck knew as early as 2001 that participants in Vioxx trials who had Alzheimer's disease were dying at three times the rate of those taking a placebo.
Articles extolling Vioxx as the â€œsuper aspirinâ€ were also a product of Merck machinations, says another JAMA article. They were actually ghostwritten from Merck's own research with doctors' "guest author" names attached as an afterthought, write Joseph S. Ross, MD, MHS; Kevin P. Hill, MD, MHS and two other authors on the basis of 250 court documents they examined.
In fact, this week Merck's ghostwriting was actually banned as part of a new, $58 million multistate settlement over deceptive Vioxx marketing -- in addition to the previous $4.85 billion -- that also requires Merck to submit future TV commercials to the FDA before airing.
Merck marketing, with Schering-Plough, of Vytorin, the cholesterol drug exposed in January as no more effective than generics, is also under investigation by the House Committee on Energy and Commerce.
In fact it was the investigation, begun in December 2007, that pried loose the results of the Enhance study that Merck and Schering-Plough had been sitting on since April 2006 -- despite clearance by consultant Michiel Bots -- while they tried to change end points, apparently to spin the data, and unloaded Schering-Plough stock, say published reports.
"I would like for the companies to explain why they didn't proceed with data analysis after Dr. Bots' independent consultation report indicated the data were 'fine,'" Rep. John Dingell, D-Mich., chairman of the committee, said to the Star-Ledger.
In May, an Energy and Commerce subcommittee hearing into deceptive drug industry marketing also looked at Merck's multimillion-dollar "cholesterol from two sources: food and family" Vytorin campaign in light of the suppressed Enhance study results.
"Many consumers may not have taken Vytorin had they been aware of the study results," said Rep. Bart Stupak, D-Mich., to Deepak Khanna, senior vice president of the Merck and Schering-Plough joint venture, according to the Star-Ledger.
Nor are other Merck drugs doing well.
Fosamax, Merck's osteoporosis drug, was already facing more than 100 suits for causing osteonecrosis of the jaw, or jawbone death -- added to its warning label in 2005 -- when a new wrinkle emerged. Women who took Fosamax were twice as likely to have atrial fibrillation, a chronically irregular heartbeat, as those who didn't, according to an article in the April 28, 2008, Archives of Internal Medicine , echoing a New England Journal of Medicine article last year.
And Singulair, Merck's allergy and asthma pill, is under FDA review for possible side effects including suicide risk.
But even as jokes appear about the number of Merck staffers required to change a light bulb -- 10 to call it a breakthrough, 10 to conference-call Wall Street, 10 to suppress evidence it's been done before and more safely, and one to change the bulb -- Merck is repeating its mistakes.
In April, it tried to launch a new cholesterol drug, Cordaptive, that combines niacin, a B vitamin that raises HDL but causes facial flushing, with laropiprant, an anti-flushing drug, without waiting for study results, like it did with Vytorin.
Not only did the company want to start making money before safety was established in a 20,000-patient study that ends in 2012, Merck admits there are "theoretical" safety concerns about laropiprant's effect on the liver, according to the Star-Ledger.
Plus, the science behind Cordaptive -- that raising HDL, or "good" cholesterol, will result in fewer heart attacks and strokes -- is no longer reliable, says the Star-Ledger's George E. Jordan.
"The utility of biomarkers was turned on its ear in a study of GlaxoSmithKlein's diabetes pill Avandia, which found it lowered blood sugar in patients but resulted in elevated heart risks," he writes. "Vytorin dramatically reduced LDL, but it worked no better at clearing clogged arteries than a generic drug five times less expensive."
No wonder the FDA rejected Cordaptive out of hand, causing Merck to cut 1,200 sales jobs and add to its anti-fan club.
Merck didn't even do simple market research. Vitamin and drug stores have been selling flush-free niacin for years. A bottle costs about $9.95.