Netracor J & J heart Drug May Raise Risk of Dying

Wed, 20 Apr 2005

A new research challenges the safety level linked with the drug ‘Natretor.’ Scios Inc., a subsidiary of Johnson & Johnson is the maker of “Natrecor.”

“Researchers say that the use of heart-failure drug Natrecor results in death within a month of treatment.”

Is this one more instance of an underpowered clinical trial permitting an unsafe drug or device to reach the market?

The argument is valid that smaller size trials minimize the harm that might accrue to research participants. BUT such trials increase the harm of undetected adverse events that will be done to those who take the drug or use the device after it reaches the marketplace. There is no avoiding the harm of adverse events that are associated with the beneficial effects of a drug or device. The only real issue is whether to let them accrue with sufficient frequency to be detected during the clinical trial or to permit them to go undetected into the marketplace to endanger hundreds, thousands, hundreds of thousands, or even millions of users.

It is commercially profitable to run less expensive and logistically simpler underpowered clinical trials in the name of minimizing adverse effects on research participants. The harm that may come later from sales of an unsafe drug or device goes undetected while big bucks are being made.

With the FDA bias against accepting evidence of the lack of safety for approved products, the drug or device manufacturer has better than even odds of continuing sales and making millions even after the lack of safety is detected, as in the present case.

The bias is revealed in Robert Temple’s assessment that there is “not a convincing case for increased mortality, but we will be looking at all available data.”

That presumption clearly is pro-industry and anti-consumer safety.

However, as a group, physicians apply the precautionary principle of medicine when they or a member of their family is the patient. Physicians do not prescribe a drug for their family members before it has been on the market for at least 2-3 years, by which time its safety will have been tested on the general population.

John H. Noble, Jr, PhD
Treasurer, AHRP
Endowed Professor, Catholic University

Contact: Vera Hassner Sharav
212-595-8974

THE WASHINGTON POST
Drug May Raise Risk of Dying, Research Says

CHICAGO, April 19 — A genetically engineered drug that was hailed as a breakthrough in the treatment of heart failure when it was approved in 2001 might actually raise patients’ risk of dying soon after treatment, researchers say.

Pooling results from three studies, the researchers found that hospitalized patients given nesiritide appeared much more likely to die in the first month after treatment than those given medication such as nitroglycerin or dummy pills.

The intravenous drug has been given to more than 600,000 patients nationwide.

Jonathan D. Sackner-Bernstein, a cardiologist at North Shore University Hospital in Manhasset, N.Y., and lead author of the study in Wednesday’s Journal of the American Medical Association, said a large study is needed.

Johnson & Johnson spokesman Mark Wolfe called the analysis inconclusive and said nesiritide is safe and highly effective. Nesiritide, sold as Natrecor, is made by Scios Inc., a subsidiary.

Robert Temple, director of the FDA’s drug evaluation office, said there is “not a convincing case for increased mortality, but we will be looking at all available data.”

C 2004 The Washington Post Company

http://www.businessweek.com/magazine/content/05_17/b3930071_mz011.htm
NEWSWEEK APRIL 25, 2005

NEWS: ANALYSIS & COMMENTARY “Off-Label” Drugs: J&J Is Pushing The Envelope

Regina Massaro, a nurse practitioner with South Bay Cardiovascular Associates in West Islip, N.Y., is something of an evangelist for Johnson & Johnson’s (JNJ ) drug Natrecor. Developed by J&J’s Scios unit, the drug was approved in 2001 by the Food & Drug Administration for the short-term treatment of heart-failure patients who are having serious problems breathing.

Massaro believes the drug may be helpful to a broader range of patients. Indeed, her boss, Dr. Larry M. Altschul, was one of the first to use Natrecor longer-term to treat patients with heart failure — an experimental therapy known as an “off-label” use of the drug because the FDA did not specifically approve it for such treatment. And Massaro says that Scios has paid to send her to meetings with doctors and nurses around the country six times in the past two years to talk about heart-failure management. Because FDA regulations ban the promotion of such off-label uses, she can’t bring up the subject of chronic Natrecor therapy herself. But Massaro says she frequently gets questions on that topic — and under the rules she is then free to discuss her experiences. “I do get asked about it a lot because we are the ones who pioneered it,” Massaro says.

By many accounts, longer-term use of Natrecor is growing. Despite questions about whether the drug could harm kidney function, and whether it could be linked to a higher mortality rate, Natrecor is expected to rack up nearly $700 million in sales this year. While no evidence has surfaced that Scios has broken the rules when it comes to marketing, the company has made moves, including the meetings by South Bays’ Massaro, that prompt discussion of the drug’s off-label uses.

In a statement, Scios says it is marketing Natrecor according to its approved label. The company is conducting trials looking at whether the drug might help people when given on a regular, weekly basis. Yet Scios says its people are not promoting that use — and the FDA has “communicated with them that they shouldn’t,” says a top agency official.

Certainly, using drugs in ways not spelled out on their label is widespread — and often proper. Frequently drugs are studied for one condition, then physicians discover other benefits. South Bay’s Altschul says he has treated 148 patients with chronic infusions of Natrecor over the past three years and has seen it cut down on hospitalizations and improve quality of life. But in the absence of full data from a large trial studying longer term infusions, the evidence so far is largely anecdotal.

In fact, others in the industry have gotten into hot water in recent years for overly aggressive marketing of off-label uses. In 2004, Pfizer (PFE ) agreed to pay more than $400 million to settle a case involving off-label promotion by a company it acquired. Yet despite such penalties, companies know that there is a lot of wiggle room in the current rules. For example, drugmakers are barred from pitching doctors directly on unapproved uses of their drugs. But if a doctor or nurse hears about an off-label use and asks a sales representative or someone like South Bay’s Massaro about it, those questions are permitted to be addressed.

There are other ways that companies can stimulate buzz about a drug. Drugmakers often sponsor continuing medical education (CME) sessions where off-label uses can be debated. A few CMEs funded by Scios in the past few years have included information on weekly infusions of the drug.

A J&J spokesman says the company knows the general topics of the CMEs it funds, and it may have some input on speakers for those sessions. But he says the company does not control the content. However, Dr. Steven Nissen, a cardiologist at the Cleveland Clinic who was also part of the FDA panel that recommended approval of Natrecor, contends the discussion of off-label uses in CMEs clearly encourages physicians to consider those treatments. In short, those messages may be fueling the growth of an increasingly controversial drug.

By Amy Barrett in Philadelphia, with John Carey in Washington

Copyright 2000-2004, by http://www.newz.in/large35.asp?catid=22&number=4391

Risk of death is linked with Natrecor
Published on : 4/20/2005 2:05:00 AM
Category : Health Care News

A new research challenges the safety level linked with the drug ‘Natretor.’ Scios Inc., a subsidiary of Johnson & Johnson is the maker of “Natrecor.”

Researchers say that the use of heart-failure drug Natrecor results in death within a month of treatment.

A report shows that 10% of people who are hospitalized for heart failure, the drug enlarge their blood vessels that reduce stress on the heart and results in shortness of breath.

The study is published in today’s Journal of the American Medical Association.

The conclusions of researchers are based on an analysis of three major studies of Natrecor that involves 485 patients and 377 controls.

Researcher Keith Aaronson of the University of Michigan says, “The individual studies were not powerful enough to look at mortality. Only by doing this analysis does real risk emerge.”

In the March Circulation, the same researchers reported a 40% to 50% increased risk of kidney problems with Natrecor.

Scios announces that it will arrange an outside board of heart experts for the evaluation of the drug’s safety.

A Food and Drug Administration review of Natrecor in 2001 says the company’s data could not “rule out a 50% increased risk” of death among patients given Natrecor.

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