Doubting Its Safety, Dr. Eric Topol and Others Want Natrecor Recalled
In the October 6, 2005 issue of The New England Journal of Medicine ("NEJM") appears a letter to the editor by Jonathan Sackner-Bernstein, M.D. and Keith D. Aaronson, M.D., two doctors who have previously expressed concerns about the safety of the controversial heart failure drug Natrecor (nesiritide). Dr. Sackner-Bersnstein and Dr. Aaronson's NEJM letter comments on an article by Cleveland Clinic cardiologist Eric J. Topol, M.D. that discussed the current clinical practice with respect to Natrecor, entitled "Nesiritide -- not verified", which was published in the July 14, 2005 issue of the NEJM.
Earlier in 2005, Dr. Sackner-Bernstein had co-authored an article which showed that Natrecor might be linked to kidney problems. This article was followed by a second one which raised questions about whether Natrecor is associated with a higher death rate than standard heart failure treatments.
In their October 2005 NEJM letter, Dr. Sackner-Bersnstein and Dr. Aaronson call for the FDA to withdraw Natrecor:
Although controlled trials demonstrate that [Natrecor] reduces symptoms of dyspnea and lowers pulmonary-capillary wedge pressure, no clinical trial has demonstrated that [Natrecor] is safe in patients with acute decompensated heart failure who have dyspnea at rest or on minimal exertion. To be consistent with federal regulations addressing the basis for drug withdrawal [footnote omitted], the FDA can and should withdraw approval for the marketing of [Natrecor]. At a minimum, an advisory panel to the FDA should address these issues in a public forum.
In a prepared statement, Scios, the Johnson & Johnson ("J&J") unit that markets Natrecor, said: "The call for the withdrawal of Natrecor is based on a hypothesis rather than hard scientific facts." This position was elaborated upon by George Schreiner, M.D., of Scios, in a separate letter to the editor appearing in the October 6, 2005 NEJM issue. In his letter, Dr. Schreiner explains why he disagrees with Dr. Topol's July 2005 NEJM article, which set forth serious questions about Natrecor safety. In relevant part, Dr. Schreiner asserts:
[Natrecor]is the only treatment for acute decompensated heart failure that has been proved in controlled clinical trials to provide a clinical benefit — improvement of dyspnea.... Safe and effective when used as labeled, [Natrecor] continues to be an important therapy for acute decompensated heart failure.
In this same issue, the NEJM allows Dr. Topol to comment on these two letters about his earlier article. In doing so, Dr. Topol joins Dr. Sackner-Bersnstein and Dr. Aaronson in calling for a Natrecor recall:
Beyond the serious questions about [Natrecor] safety, there have been no trials to demonstrate clinically meaningful efficacy. This would require a reduction of death or repeated hospitalization for heart failure at 30 days, and such a trial has not been initiated, despite the drug having been approved more than 4 years ago. Clearly, the minimal criteria for safety and efficacy have not been fulfilled, and I agree that drug withdrawal, until such time validation is assured, is a reasonable proposition.
When the FDA was asked for comment about the growing Natecor safety controversy, Dr. Robert J. Temple, the agency's associate director of medical policy, said that there has not been any new information on Natrecor since its approval in 2001 that would cause the FDA to revisit its decision to approve Natrecor.
Dr. Topol, who is the chief of cardiovascular medicine at the Cleveland Clinic Foundation, doubts that the FDA will order a Natrecor recall:
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.
In turn, the FDA's Temple rejected any suggestion that the FDA would resist ordering J&J and Scios to withdraw Natrecor simply to avoid having the agency look bad. "The way you look most stupid is by failing to recognize a problem when it should be recognized," Temple said.
No doubt, we will be reading more about the controversy over Natrecor's safety -- not to mention the "off-label" prescribing issue.
(Posted by: Tom Lamb)