The government should halt sales of the congestive heart failure drug Natrecor until a large study proves it significantly benefits fragile patients, a leading cardiologist said.
Aggressive marketing has put sales of the drug on track to double this year to $700 million, even though it costs 50 times more than standard therapy and increases patients’ risk of death and kidney damage, Dr. Eric J. Topol wrote in a commentary published today in the New England Journal of Medicine.
Natrecor ”has not yet met the minimal criteria for safety and efficacy,” wrote Topol, chair of the Cleveland Clinic’s department of cardiovascular medicine.
Topol, who submitted the article at the request of the journal’s editors, earlier raised concerns about such new-generation painkillers as Vioxx, which Merck & Co. stopped selling last fall due to safety concerns.
In today’s article, Topol criticized Scios Inc., a subsidiary of Johnson & Johnson, for promotion that included advising doctors how to bill Medicare for Natrecor uses not approved by the Food and Drug Administration. He faulted the agency for setting a ”low threshold” for approval, not warning patients of increased risks and not pressuring Scios to conduct definitive safety trials.
The FDA approved the drug in 2001 for intravenous use in hospitalized patients whose condition is so grave they gasp for breath while at rest or during minimal activity. Approval was based on a trial of 489 patients that compared Natrecor, whose generic name is nesiritide, to placebo and intravenous nitroglycerin. It showed that within three hours the drug reduced breathing problems caused by fluid buildup in the lungs and improved a measure of cardiac function thought to be significant at the time.
But Topol’s commentary said the same study also showed people receiving Natrecor had lengthier hospital stays and higher death rates 30 days after using the drug.
FDA’s rapid approval process for Natrecor contrasts with the strategy of European drug regulators who are waiting for the results of a 1,900-patient trial before deciding whether to allow the drug’s sale. A similar study also should be conducted in the United States to prove Natrecor reduces death rates or has other durable clinical value, Topol said.
”The question is why should it be given at all right now when we don’t even know its safety,” he said in an interview.
The FDA said a halt in sales is unlikely, and an agency official said delaying approval until Scios could prove the drug’s impact on mortality would not have been reasonable.
”A short-term treatment with nesiritide is expected to improve the increased symptoms of decompensated heart failure,” said Dr. Robert Temple, FDA’s associate director of medical policy. ”A long-term effect on survival would be nice, but symptomatic improvement is of value by itself.”
Temple said the FDA knew before approving the drug that some trials raised questions about Natrecor’s impact on kidneys and mortality, but ”it did not appear to represent a real risk,” he said. ”Had we thought it did, we would have asked for additional data.”
The criticism from Topol comes as Medicare managers worry about ballooning reimbursements for Natrecor in outpatient clinics where people can receive dozens of treatments costing taxpayers at least $500 per session. Hospitalized patients typically receive the drug a few times as stopgap therapy to relieve their symptoms and to give doctors time to consider long-term treatments.
Scios’s reimbursement guide suggests doctors use Medicare codes that treat the heart drug like chemotherapy. That permits them to bill for larger Medicare reimbursements. They can include a professional fee that amounts to an additional $172 for the first hour the drug is given to a patient, and they are allowed to bill $408 for eight hours of observation, Topol noted in the article.
He said that through its marketing Scios has placed Natrecor in a drug class of its own.
”Cardiologists have never made revenue by giving a drug to a patient,” he said in an interview. ”This is a new, new thing.”
Johnson & Johnson spokesman Mark Wolfe said the company ”absolutely takes issue” with the assertion that it promoted regular, scheduled outpatient use of Natrecor. He also said such use does not significantly benefit the company.
Halting Natrecor sales would hold it to a higher standard than other drugs, like nitroglycerin, that without clinical proof are used to treat the same gravely ill patients, Wolfe said.
Boston University’s Dr. Wilson S. Colucci said he has used Natrecor in a clinical trial, as well as for select University Medical Center patients. He reviewed the drug’s safety data in June as a member of a panel that met at the urging of Scios.
”I very much want to be sure that we get it right,” said Colucci, chief of cardiovascular medicine. He said there has been ”excessive abuse” of Natrecor by some doctors, but fears there may be an overreaction to the problem.
”When used in the right patients, in the right way, it’s an important” treatment option, Colucci said.
Dr. Clyde W. Yancy, a University of Texas Southwest Medical Center professor of medicine, called Topol ”a strong voice in cardiology,” but he defended Natrecor’s effectiveness.
Yancy is now leading a clinical trial involving 900 patients to test Natrecor’s safety and efficacy as an outpatient treatment.
Medical journal articles critical of Natrecor published this spring slowed patient recruitment rates for the trial during May, Yancy said.