You know that a drug study has gone very, very bad when you can't find out its results without a congressional inquiry.
Last month the House Committee on Energy and Commerce demanded information about the Enhance clinical trial. Some data was released on Jan. 14, and it's been a popular topic on television news since then.
Simvastatin is a well-studied medication, and like other statins, such as Pfizer's (NYSE: PFE) Lipitor and AstraZeneca's (NYSE: AZN) Crestor, works on receptors in the liver to lower cholesterol levels.
Because Vytorin lowers cholesterol levels more effectively than other cholesterol drugs, and because heart patients with lower cholesterol levels tend to do better in clinical trials, many cardiologists felt that Vytorin was an excellent medication to prescribe to patients with heart disease.
It is certainly well marketed. Surely you've heard the commercial: "There are two sources of cholesterol: food and family. Vytorin treats both." Sales of Zetia, approved in 2002, and Vytorin, approved in 2004, are around $5 billion annually, making it one of the world's best-selling drugs.
Although multiple studies prove that Zocor not only lowered cholesterol levels but also lowered the risk of heart attacks, there are no similar studies for Zetia or Vytorin that demonstrate clinical benefits. If adding Zetia to Zocor (to make Vytorin) does not improve patients' clinical outcomes more than just Zocor, then why take the more expensive medication?
The Enhance study was designed to show a benefit among patients taking Vytorin, primarily by documenting less buildup of plaque in the carotid arteries, a surrogate for the progression of coronary artery disease.
In the trial, 720 patients with a genetic abnormality that caused extremely high levels of LDL cholesterol were randomized into two groups. One received Vytorin (Zocor plus Zetia), and the other group received Zocor. The Vytorin group had a statistically lower level of LDL cholesterol, as expected; the incidence of serious side effects was low and similar in both groups. So far, so good.
While not statistically significant, there was evidence of more thickening of carotid arteries in patients in the Vytorin group than in the Zocor group. The Vytorin group also had a minuscule, statistically non-significant, higher number of deaths, heart attacks, and angioplasty or bypass surgeries. Although the number of patients studied is small, and the type of patients studied is different from those usually prescribed the medication, the outcome trends went in the wrong direction.
The American College of Cardiology released a statement recommending that major clinical decisions not be made on the Enhance study results alone. Leading cardiologists had differing opinions.
Dr. Robert Califf, noted Duke University cardiologist, stated that he plans to continue to take Zetia. "I don't see any signal of toxicity from this trial, so that is reassuring. There's no indication that it's working, either, but that was also the case before Enhance came out. For me, the fact it lowers LDL and does not appear to have side effects is enough until definitive outcome data become available."
Dr. Steven Nissen, Cleveland Clinic cardiologist -- of anti-GlaxoSmithKline's
Adding salt to the wound, the biggest headache might come from Congress as it begins to investigate why it took so long for the Enhance results to be made public. Congress is also investigating those ubiquitous Vytorin ads.
In an election year, hearings about who knew what details of the study, and when, can only be bad news for prescription sales.
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