Noted experts fear Vioxx-like scenario is about to be repeated with potentially deadly results for those who would take the drug that is about to be approved for sale.
An eagerly awaited diabetes drug, which is nearing final approval by the FDA, significantly increases the risk of heart attacks, strokes, or death, researchers reported in a study published in the Journal of the American Medical Association yesterday.
The study is yet another situation that raises serious questions concerning the reliability of the FDA’s drug approval process and whether it is unduly biased in favor of the pharmaceutical industry.
Muraglitazar, which would be marketed as Pargluva by Merck and Bristol-Myers Squib, was recommended for approval last month by an advisory committee from the Food and Drug Administration.
The drug was highly anticipated by diabetes experts because it tackles both high cholesterol and high blood sugar; two serious problems suffered by the 18 million people with diabetes who are at an elevated risk of developing heart disease.
The new study used the very same data the FDA panel and staff examined. While the FDA panel voted 8-1 for approval of the drug, the study researchers identified several serious health concerns about the drug based on that data.
Looking at 2,374 patients who took Pargluva, and 1,351 people who took either a placebo or a rival drug, Actos, researchers found that Pargluva-treated patients had almost a threefold greater risk of heart failure, heart attack, stroke, and death.
"Ten of 1,000 patients would die, have a heart attack or a stroke," said lead author Steven Nissen of the Cleveland Clinic. "Those are serious irrevocable events."
The new study comes from the highly respected researchers at the Cleveland Clinic, the same team that broke the story on the cardiovascular dangers of Merck’s anti-inflammatory drug Vioxx.
Dr. Nissen has often been an outspoken critic of the methods and motives of the pharmaceutical industry and the FDA with respect to the entire drug approval process and after-approval monitoring of drugs for dangerous side-effects.
"These findings are particularly concerning because the significant excess of adverse events was observed after only limited drug exposure ranging from 24 to 104 weeks," Nissen, and colleagues report. "Real-world exposure would likely substantially amplify the risk. Taken as a whole, these data demonstrate that [Pargluva], if approved by the FDA, would constitute an unacceptable patient hazard."
The FDA announced that Pargluva was ready for release on the market earlier this week.
And due to the severity and prevalence of diabetes, there is no doubt that the drug’s manufacturers and marketers are eager to capitalize on the demand for the dual-acting, potential powerhouse drug.
But at the same FDA advisory committee meeting where the drug was recommended for approval by a vote of 8-1, even the FDA’s own analysts identified evidence of cardiac risk.
In a scenario similar to the Vioxx narrative, however, the analysts did not highlight this cardiac risk to patients as significant, except in cases where the drug was used in conjunction with other therapies.
Experts from Bristol-Myers concluded that there was no significant increase in heart risk for patients. The analogy to the Vioxx debacle is inescapable. (As Yogi Berra would say; “This is like deja vu all over again.”)
The risks posed by Pargluva may not end with cardiovascular problems. A JAMA editorial by James M. Brophy, MD, PhD, of McGill University in Montreal, released along with the Cleveland Clinic’s report, says that patients who took Pargluva could be as much as three times more likely to get cancer than patients who took placebos, and that more widespread use could cause this link to grow significantly.
Brophy agrees with Nissen and the research team at the Cleveland Clinic’s recommendation of a wide-scale, pre-marketing safety trial to further examine Pargluva.
The potential for Pargluva and other drugs like it is vast and offers hope to the many millions of Americans who suffer the life-threatening diabetes. But a hasty or premature release of the drug to eager patients, without fully understanding or revealing the significant health risks, could have devastating consequences.
In the wake of the law suits and backlash against Merck and the FDA over the Vioxx scandal, the pharmaceutical industry as well as the FDA must recognize the simple fact that they each owe the public (and not investors or contributors) the highest duty to take every precaution before releasing a potentially harmful prescription drug.