The failure of Xigris to show an effect on mortality in a clinical trial of patients with septic shock has prompted the manufacturer to withdraw the drug from the United States and other countries where it is approved, Eli Lilly & Co. announced on Oct. 25.
Xigris (drotrecogin alfa [activated]), a recombinant form of human activated protein C, was approved in the United States in 2001 for the reduction in mortality in adults with severe sepsis who have a high risk of death. It was approved in 2002 in the European Union for the treatment of adults with severe sepsis and multiple organ failure "when added to best standard care."
The PROWESS-SHOCK study, conducted as a condition for continued approval in Europe, showed that treatment with Xigris did not meet the primary end point, a significant reduction in 28 day all-cause mortality in patients with septic shock, Lilly announced in a statement.
"While there were no new safety findings, the study failed to demonstrate that Xigris improved patient survival and thus calls into question the benefit-risk profile of Xigris and its continued use," Dr. Timothy Garnett, senior vice president and chief medical officer at Lilly, said in the statement. Xigris should be stopped in patients currently being treated with it, and the drug should not be started in new patients, he added.
More details of the study were provided in a statement released by the Food and Drug Administration on the withdrawal, which said that the preliminary analyses of the data found that the 28-day all-cause mortality rate was 26.4% (223/846) among Xigris-treated patients, compared with 24.2% (202/834) among those on placebo, which was not a statistically significant difference.
In 2009, the FDA issued a statement about an ongoing safety review of Xigris, regarding the increased risk of serious bleeding events and deaths in a study of patients treated with Xigris who also had risk factors for bleeding at baseline. The increased risk of bleeding associated with Xigris treatment was a significant safety issue associated with the drug, which was contraindicated in patients with active internal bleeding and other situations in which bleeding could result in significant morbidity or death.
For questions about Xigris, the company can be contacted at 800-LillyRx or www.Lilly.com.