) controversial heart failure drug Natrecor shows no signs of abating. In a letter in the Oct. 6 issue of the New England Journal of Medicine, two physicians who had authored papers raising questions about the drug's safety are now calling for the Food & Drug Administration to withdraw Natrecor. "There is a new acting commissioner [Andrew C. von Eschenbach] at the FDA," says Dr. Jonathan Sackner-Bernstein, one of the authors. "This is a terrific litmus test to see whether he is really concerned about the safety of drugs that are on the market."
Dr. Robert J. Temple, associate director of medical policy at the FDA says the papers that have raised safety questions about Natrecor don't take into account all the trials conducted on it. And he says there hasn't been any new information on Natrecor since its approval in 2001 that would cause the FDA to revisit its decision to approve the drug.
In a statement, Scios, the J&J unit that markets Natrecor, said the drug is one of the few options doctors have for treating patients who are suffering episodes of severe breathing difficulty associated with heart failure. "The call for the withdrawal of Natrecor is based on a hypothesis rather than hard scientific facts," Scios said.
"LEADERSHIP STRIFE." Still, the clamor for the drug's withdrawal is likely to bring more unwanted attention to the controversy surrounding Natrecor. Earlier this year Sackner-Bernstein co-authored a paper that showed it might be linked to kidney problems. That was followed by a second paper that raised questions about whether Natrecor is associated with a higher death rate than standard treatments.
The drug is drawing other vocal critics as well. Among them: Dr. Eric J. Topol, chief of cardiovascular medicine at the Cleveland Clinic Foundation. Topol, who was an early critic of Merck's (MRK
) now-withdrawn painkiller Vioxx, also believes Natrecor should be pulled. But he says, "With all the leadership strife at FDA and the unwillingness of those people who were involved to admit the potential of being too lenient [in approving the drug], I'm not optimistic."
The FDA's Temple rejects any suggestion that the agency would resist pulling the drug simply to avoid looking bad. "The way you look most stupid is by failing to recognize a problem when it should be recognized," Temple insists.
UNAPPROVED USE. Certainly J&J has been in damage-control mode for months. In April it convened a panel of outside experts led by noted Harvard Medical School professor Dr. Eugene Braunwald to review Natrecor's safety and give guidance on what sort of additional clinical trials needed to be done. In June the panel made a series of recommendations, including urging Scios to move ahead on a planned large trial aimed at answering questions about the drug's impact on death rates. A Scios spokesman says the company is in the process of designing and seeking FDA guidance on such a study.
The panel also urged Scios to limit the ways in which Natrecor was being used. It was originally studied in hospitalized heart-failure patients who were suffering from labored breathing. But in recent years some physicians have given Natrecor on a regular basis to heart-failure patients who weren't suffering from serious breathing problems in the hope it would prevent them from landing in the hospital. Most of the data on that sort of use are anecdotal, and that use wasn't approved by the FDA.
Scios says it hasn't promoted that sort of use, but its marketing practices are under scrutiny. In July, Scios received a subpoena from the U.S. Attorney's office in Boston asking for documents related to Natrecor's sales and marketing. Scios says it's cooperating with the request.
Still, the J&J panel clearly wants Scios to steer doctors away from prescribing Natrecor for those regularly scheduled treatments. In August, it rolled out a program to retrain its sales force, and it began running ads in medical journals aimed at ensuring the drug is being used appropriately. But as more voices call for Natrecor's withdrawal, it looks like these efforts won't be enough to keep calm the critics.
Barrett is BusinessWeek's Philadelphia bureau chief