WEDNESDAY, June 25, 2002 (HealthDayNews) -- Controversy is still boiling around a drug derived from human protein nearly a year after the U.S. Food and Drug Administration (FDA) approved it to treat severe and often fatal blood infections.
The drug, a bioengineered version of a molecule called activated protein C or drotrecogin, now is approved only for the most severe cases of sepsis, a blood infection that affects perhaps 750,000 Americans a year and kills 225,000 of them. It has been a center of intense discussion since the FDA gave its approval last November, after a 20-member advisory committee divided evenly on the question.
At the moment, activated protein C is used only in the most severely affected patients. The international study that led to its approval showed it reduced the death rate in those patients to 24.7 percent, compared to 30.8 percent for patients who got a placebo.
Eli Lilly and Co., which markets the drug, has agreed to conduct three trials including 13,000 patients to get answers to some outstanding questions, says Dr. Jay P. Siegel, director of the Office of Therapeutic Research and Review at the FDA's Center for Biologics Evaluation and Research.
One of those studies will enlist 11,000 patients to see whether the protein can help lower-risk patients, Siegel writes in an overview article in tomorrow's issue of The New England Journal of Medicine that includes at least six contributions centering on the drug. Another study will evaluate its effect in children with sepsis, and the third will combine the protein with low-dose heparin, used to reduce the blood clotting that contributes to the deadly effects of sepsis.
It's hard to say when results of those trials will be available, Siegel says. "It takes time to recruit, time to treat, time to report," he says. Meanwhile, he says, the recommendation that it be used only in high-risk patients remains in effect.
Even that use is questionable, says Dr. Richard P. Wenzel, chairman of the department of medicine at Virginia Commonwealth University and author of a commentary in the journal.
"My feeling is that the drug has some effect, but I think it is modest," Wenzel says. One objection, shared by others in the field, centers on the fact that Lilly changed the rules in the middle of the study that led to approval, using a different criterion for patient eligibility. At the same time, Lilly began to use a different human cell line to produce the protein, which raised questions about whether that change altered the drug itself.
When the initial results were released, the drug was referred to as a "landmark" in critical-care treatment. It was only after the study was completed, however, that the FDA did an analysis concluding that the beneficial effect was concentrated in high-risk patients.
"The FDA is on thin ice to have performed a post-analysis and used data from that analysis to approve the drug," Wenzel says. "Also, subsequently to use such a physiological score as an indication for drug use is risky. We clearly need more data in the midst of this controversy to show that we have an efficacious drug."
The drug is efficacious, Siegel says -- not as effective as might be hoped, but nevertheless valuable. "We all hoped for something like a miracle cure," he says. "But the fact is that many of the drugs we use today have only a modest effect."
The ultimate consideration, Siegel says, is that "there is not a lot out there for these septic patients. It is a benefit that we have something to use."
What To Do
You can learn more about sepsis from KidsHealth or the Lilly site Sepsis.com.
