Natrecor: A History of Shady Practices

It's incredulous that a drug approved for very limited use could actually be given to a wide range of people. Yet this is what happened in the case of Natrecor (nesiritide), a drug approved by the FDA for emergency use only in hospitals.

Somehow, Natrecor managed to evolve from emergency-only to preventative-maintenance use, despite not receiving FDA approval to do so.

Eric J. Topol, MD, asked in the July 14, 2005 issue of the New England Journal of Medicine "How can a drug that is associated with higher rates of both renal dysfunction [kidney problems] and death than placebo - and that costs 50 times as much as standard therapies, and for which there are no meaningful data on relevant clinical end points - be given to more than 600,000 patients and be promoted throughout the United States for serial outpatient use, an indication not listed on the label?"

In order to answer this question, we must look at the history and marketing of Natrecor.

History of Natrecor
Natrecor was approved for use in August 2001 and introduced that fall. It was approved only in a select group of heart failure patients. Those patients had to have shortness of breath while at rest and they had to be in a hospital. However, the label on Natrecor did not indicate that it was meant for hospital use only. Scios, a division of Johnson and Johnson, then began focusing on the type of patient who would benefit from outpatient use of Natrecor. Following this, outpatient clinics offering "infusion treatments" opened up. Because many of the patients were age 65 or older, they were eligible for Medicare, which covered Natrecor in most states.

Concerns about Natrecor
In his letter to the New England Journal of Medicine, Dr. Topol expressed concern that Natrecor had not been properly studied to assess whether or not it was safe. He wrote, "In my view, nesiritide has not yet met the minimal criteria for safety and efficacy. Until a trial definitively proves that this drug reduces the risk of death or repeated hospitalization for heart failure, there will be questions about the appropriateness of the drug's use or even commercial availability."

One of the main concerns is that Natrecor has troubling safety issues but has not been shown to be effective compared to other, similar drugs. According to the New York Times article, "Many other doctors contend that much cheaper alternatives to Natrecor - like nitroglycerin, as well as Lasix and its generic variants - can work just as well as an emergency treatment for heart failure."

Although it may not be more effective than other drugs, it may be more deadly. A study by Sackner-Bernstein found an 81% increase in the death rate when Natrecor was taken as opposed to a placebo. Furthermore, follow-up on another study (cited by Dr. Topol) shows that Natrecor had an adverse effect on 30-day mortality rates. The mortality rate in the nesiritide group was 7.1 percent, compared with the placebo group's 4.8 percent.

Sackner-Bernstein also co-authored a paper that showed Natrecor might be linked with kidney problems.

Some groups have called for further research into the safety and effectiveness of Natrecor. A study published in the Journal of the American Medical Association concluded that "The possibility of an increased risk of death should be investigated in a large-scale, adequately powered, controlled trial before routine use of nesiritide for acutely decompensated heart failure."

Marketing of Natrecor
Scios Inc, the division of Johnson & Johnson responsible for Natrecor, has faced strong criticism over how the drug was marketed. In July 2005, the US attorney's office in Boston served a subpoena giving it access to documents that show how Natrecor was marketed. This came after criticisms that the drug was being regularly administered for outpatient heart treatment. The FDA has not yet approved Natrecor for this use.

Natrecor was approved to be used for hospitalized patients who had difficulty breathing even during periods of rest or minimal activity. However, some doctors claim that Scios sales representatives gave them brochures that detailed the opening of outpatient clinics at which the drug could be regularly given to patients. Although it is not illegal for doctors to prescribe drugs for off-label uses, it is illegal for companies to promote drugs for such use.

An article in the May 17, 2005 edition of the New York Times argued that patients at the outpatient clinics could receive doses of Natrecor weekly over a period of several months. Such treatments could cost over $600 a session, more if the doctor charged an examination fee.

For its part, Scios representatives deny that they have promoted Natrecor for such use. A letter posted on the FDA website states, "We understand that NATRECOR® is also being administered as intermittent and scheduled infusions to treat severely ill congestive heart failure patients, particularly in the outpatient setting. Although a clinical development program is currently underway in this setting (FUSION II trial), Scios does not recommend NATRECOR® for this use at this time."

The company also gave doctors access to a toll-free hotline that could be used to help doctors looking for Medicare reimbursement attain billing codes and forms.

In addition to improperly marketing Natrecor, The New York Times reported June 28, 2006 that Scios gave an organization known as the Midwest Heart Foundation more than $300,000 for 2003 and 2004. The article notes that some of the supporters of Natrecor included doctors from Midwest Heart. These doctors participated in studies of Natrecor and also used it in outpatient treatments.

Scios has plans to go ahead with new studies of Natrecor in order to get new information on the effectiveness of the drug. Some researchers believe that until those studies are completed, Natrecor should only be used when other treatments are not available.