WEDNESDAY, July 13, 2005 (HealthDay News) -- A hard-hitting article in one of the nation's most prestigious medical journals claims the maker of the widely used heart failure drug Natrecor is circumventing concerns over patient safety while watching revenues soar.
One of the country's top cardiologists asserts that Scios Inc., a subsidiary of Johnson & Johnson, continues to aggressively market Natrecor even as the drug comes under increased scrutiny for links to kidney failure and death.
"It's a pattern. We saw it with Vioxx and some of the cox-2 inhibitor drugs, and we're seeing it now with Natrecor," said Dr. Eric Topol, author of the article, which appears in the July 14 issue of the New England Journal of Medicine. "The twist here is that the aggressive marketing is through the medical community. With other drugs, it's direct-to-consumer advertising."
"Other than that, we have the themes of manuscripts published in prestigious journals with key omissions of data, the FDA approving drugs without mandating key trials, and companies aggressively pursuing sales and marketing of their drugs," continued Topol, who is chairman of the department of cardiovascular medicine and chief academic officer at the Cleveland Clinic in Ohio.
Natrecor (nesiritide) was approved by the FDA in 2001 for the treatment of acute, decompensated congestive heart failure, a stage of heart failure characterized by increased severity and long hospital stays. According to the company, it is the first member of a new drug class, human B-type natriuretic, and is manufactured from E. coli bacterium using recombinant DNA technology.
Today, tens of thousands of patients in the United States are receiving "tune-ups" with the drug on an outpatient basis, an indication for which the drug is not approved, Topol said. In fact, the drug, which costs about $500 per dose, is now being used 10 times more often in outpatient clinics than in acute hospital settings.
Sales for Natrecor are projected to be $700 million for 2005, Topol wrote, nearly double what they were last year.
According to Topol, studies have shown that Natrecor contributes to kidney dysfunction, and may even cause death. One trial found kidney problems were occurring at a rate three times that found in patients taking a placebo. Another trial found a 50 percent increase in the risk of death at 30 days. And when data from three trials was pooled, researchers led by Dr. Jonathan Sackner-Bernstein, a New York cardiologist, found an 81 percent increase in the death rate vs. a placebo.
"It hardly does any better than placebo," said Sackner-Bernstein, associate chief of cardiology and the director of the Heart Failure Program at St. Lukes-Roosevelt Hospital Center, in New York City.
He added that he had great difficulty getting his data published in any medical journals, although two Natrecor studies conducted by his team did eventually appear in Circulation and the Journal of the American Medical Association earlier this year. He also took his data to the company.
Particularly troubling to Topol and others has been the aggressive marketing undertaken by the company even after safety issues had been raised.
According to the article, Scios is encouraging physicians to start their own "infusion centers," which would be billed to Medicare; it has also set up a toll-free telephone hotline for "Natrecor Reimbursement Support" and published a 46-page reimbursement and billing guide that provides doctors with specific Medicare billing codes.
"If a drug is off-label, the FDA basically takes a blind-eye approach," Topol said. "There's a very fuzzy line about promotion. The company would say we're not promoting the outpatient tune-up. Well, how come they have a hot line, and any doctor can call and set something up? Is that not promoting it? Come on, help me. Where do you draw the line?"
A spokeswoman for the FDA said, "The safety problems that were identified [with Natrecor] were fully considered by FDA and the advisory committee, the appropriate information was put into the labeling and FDA was also advised that labeling has been updated with information for all the trials on the mortality issue."
In June, an expert panel convened at Scios' request recommended additional trials to assess the safety and efficacy of Natrecor. The panel also stated that use of the drug should be restricted to patients coming to the hospital with acutely decompensated congestive heart failure (ADHF).
"Scios shares Dr. Topol's commitment to the appropriate use of medicine for acute decompensated heart failure," Scios spokesman Mark Wolfe said late Wednesday. "Scios does not recommend, nor do we promote, Natrecor for scheduled intermittent use in patients with ADHF." Wolfe noted that 95 percent of Natrecor sales since the drug's launch has been to hospitals.
"Dr. Topol's piece doesn't offer new data regarding Natrecor, and it also contains some inaccurate statements," Wolfe added.
An example of an inaccurate statement, Wolfe said, was regarding higher death rates. The label has also been updated, he said. And the reimbursement guide was developed to clear up confusion.
"The reimbursement guide was developed to provide hospitals and other medical staff with comprehensive information, not selective information, to accurately code a patient's condition under Medicare requirements. There was significant confusion in terms of how physicians should bill," Wolfe said. "These kinds of guides are not uncommon. They don't encourage inappropriate use of medicines."
Scios has also been working with the FDA to implement a physician education program to comply with the expert panel's recommendations, and Wolfe said that a letter they're in the process of disseminating has been posted on the Web site in the past day or two.
Last but not least, he said, "Scios will be conducting a large outcomes trial as part of a recommendation from the panel. We're in the process of designing and getting approval from the FDA. That doesn't happen overnight."
If Scios was committed to doing more research, Sackner-Bernstein said, "I would have expected to hear more from them by now... I would think Johnson & Johnson would like to prove to the world that they do care about patients, that they do have ethics, and it's pretty clear to me that it's not their motivation."
The ideal situation, as Sackner-Bernstein sees it, would have been for him and others to go to the company (which they did), and for the company and FDA to have worked things out.
"The fact that the FDA doesn't have much enforcement capability is a problem," Sackner-Bernstein said. "Then again, where are the ethics? The people involved at Scios and others who knew about this data should be hanging their heads. There's no other way to look at it. What is wrong with everybody that you've got a drug that increases renal dysfunction and death, and costs 50 times as much as a regular treatment, and yet it's given to hundreds of thousands of people?"
The American Heart Association provides a detailed explanation of heart failure.