For anyone reading pharmaceutical news, this week was All Vytorin, all the time.
For many, the plot is twisted but familiar. Vytorin is a combination drug of Merck’s Zocor (a cholesterol drug in the simvastatin family) and Schering-Plough’s Zetia, an ezetimibe, which was said to clear arterial plaque in a different way than traditional cholesterol-lowering statins. In October 2007, some reporters noticed that the ENHANCE trials wasn’t registered on ClinicalTrials.gov, even though all trials for FDA-approved drugs are required to be registered there before they enroll participants. In November, calls for the ENHANCE results, which had been completed two years earlier, grew louder. Merck and Schering-Plough, which were splitting the spoils, made the unorthodox announcement that they were changing the primary endpoint (what the trial is measuring), and would have results in time for the 2008 annual meeting of the American College of Cardiologists.
And at that ACC meeting this past weekend, an expert panel of five cardiologists finally disrobed the emperor. Even with the changed primary endpoint, Vytorin showed no significant plaque-dissolving benefit over plain ol’ simvistatin. Now it looks as though the drug companies backdated the start date of another Zetia trial, IMPROVE-IT. Emails about suppressed data, vexed researchers, and calls for prescribers to return to older, proven drugs are daily in the news.
Maybe it’s just the times, but we can’t help noticing some similarities between what Forbes.com calls the ‘Vytorin Saga’ and the Bear Stearns bail-out and its myriad financial aftershocks.
Both the Bear and Vytorin nosedives come out of the same economic zeitgeist: in recent years, pharmaceuticals and investment banks have grown profits largely with risky delay tactics – in the case of pharmaceuticals, a cocktail of combo and me-too drugs that magically create new patent exclusivity with the same molecules, and legal battles to keep generics out of the market. In the case of investment banks, those delay tactics included trading on products made up of no-look mortgages given to people without the means to pay. There was time to be bought, and to be sold again at a premium.
As a product, Vytorin is much like a sub-prime mortgage – an unproven way to capture share in a market that had been largely tapped (all the viable mortgage candidates already owned, and were taking out multiple home equity loans to redo their kitchen). With Zocor going off patent, Merck needed a way to keep share in a market that seemed to be expanding infinitely, or at least as far as the shareholders eyes could see. Like homeowners and housing prices, the number of Americans with high cholesterol just kept going up. And up and up. Why not tap into that? Share the profits? The proof – that could come later, once market share was secured. A trial was started, and finished. There was time, certainly time to massage the data – and the start dates, and the end dates, and the primary endpoint. Two years passed, and over $5 billion of Vytorin was sold.
But like Bear’s last few days, Vytorin was brought down when someone finally looked at what was there. “I’m not saying this drug should go away, but it should definitely go to the end of the line,” Dr. Harlan Krumholz told MedPage Today. Dr. Krumholz, a Yale cardiologist, was a member of the panel that spoke on the ENHANCE trial last week. Other prominent cardiologists have called the drug ‘a last resort.’
It’s important to remember that the proof on Vytorin had always been there – or, more accurately, never been there. The key for the subprimes was to buy and sell, but not to ask. The key to Vytorin’s success was, well, not to ask. At least not yet.
But now we are all asking – not just regulators and cardiologists, but homeowners, patients, grocery-shoppers, and members of a public daily medicated but rarely squared with.
Policymakers have begun investigations and hearings. Patients are asking their doctors, and their doctors are retracting their prescribing pens and going back to the basics – in this case, tried-and-true statins. In the contracting financial markets, lending has tightened, and investors are going back to other basics – bonds, banks with demonstrated liquidity. It seems the moment for evidence-based lending and medicine is at hand.