Scios Announces Study To Address Safety Issues But Results Not Expected For Several Years
In the October 1, 2006 issue of the medical journal Pharmacotherapy is an article which emphasizes the need to resolve the safety issues surrounding the heart failure drug Natrecor (nesiritide). The Medline abstract for "Nesiritide: harmful or harmless?", by MP Dorsch and JE Rodgers, succinctly sets forth the current situation:
Recently, two meta-analyses raised the question of safety with [Natrecor] therapy, specifically an increased risk of renal dysfunction and mortality. Although several studies generated information regarding the potential role of [Natrecor] in various settings, the questions raised by the meta-analyses are concerning. Our hope is that future clinical trials will address the concerns raised and provide a better understanding of the role of [Natrecor] in the management of acute decompensated heart failure. Until these data are available, [Natrecor] use should be limited.
As for those two recent studies, Dr. Keith Aaronson, of the University of Michigan, and Dr. Jonathan Sackner-Bernstein, of the New York research firm Clinilabs, re-examined data from two previous clinical trials involving heart drug Natrecor. Their analysis, set forth in the September 26, 2006 edition of the Journal of the American Medical Association, led Aaronson and Sackner-Bernstein to conclude that Natrecor is associated with a significant increased risk of death. According to a September 29 report in the Contra Costa Times, Dr. Sackner-Bernstein reached this conclusion: "There appears to be a very strong association between the use of nesiritide and the risk of death within 30 days".
In the same newspaper article, a spokesperson for Scios -- a unit of the drug company Johnson & Johnson (J&J), which is responsible for Natrecor -- took issue with the assertion by Aaronson and Sackner-Bernstein that there is an increased risk of early mortality in patients who used Natrecor at recommended starting doses.
Coincidentally, earlier in September 2006 Johnson & Johnson had announced the favorable results of a Scios-sponsored study which looked at Natrecor use in 279 heart failure patients who underwent heart bypass surgery. But according to a September 11, 2006 Reuters article, one of the investigators for the Scios study, cardiac surgeon Dr. John Luber, said these results had to be viewed in context. Reuters quoted Dr. Luber as stating "I do not think it is absolute vindication, but I do think it is a light a the end of the tunnel." The Reuters article continued:
[Dr. Luber] said a larger study will be needed to test what patients might best benefit from [Natrecor]....
An independent expert panel had recommended a wider study to evaluate the safety of the drug more than a year ago.
Last week, Scios said it named Duke Clinical Research Institute as the independent research organization that will lead the trial, which the company said will start in the second half of 2007.
In more detail, Robert M. Califf, director of the Duke Clinical Research Institute at Duke University in North Carolina, will lead a Scios-sponsored clinical trial intended to test the safety and efficacy of Natrecor. This announcement came more than 15 months after the call for a study to investigate the issue of whether Natrecor increases the risk of death or kidney failure within 30 days of treatment among patients hospitalized with acute heart failure. According to a September 8, 2006 article in The Wall Street Journal:
The study, whose precise design has yet to be finalized, is expected to first evaluate safety and efficacy at 30 days after treatment. Enrollment of patients -- about half from North America and the rest from elsewhere around the world -- is expected to begin in the first half of next year. Dr. Califf said the first results should be ready in two to three years.
Until the safety issues are resolved, as advised by Dorsch and Rodgers in their article "Nesiritide: harmful or harmless?", it seems that the use of Natrecor should be limited.
(Posted by: Tom Lamb)