The FDA has announced that Eli Lilly has voluntarily withdrawn drotrecogin alfa (activated) (Xigris) after a recently completed trial (PROWESS-SHOCK) in patients with severe sepsis and septic shock failed to show an increase in survival in those treated with the drug.1 Drotrecogin alfa is a recombinant form of human activated protein C. Native activated protein C inhibits coagulation, increases fibrinolysis and has anti-inflammatory properties. FDA approval of Xigris (for patients with severe sepsis at high risk of death) was based on a single study (PROWESS).2 Post-marketing studies found a higher rate of bleeding than that reported in PROWESS.3,4

1. FDA Drug Safety Communication: voluntary market withdrawal of Xigris [drotrecogin alfa (activated)] due to failure to show a survival benefit. Available at http://www.fda.gov/Drugs/DrugSafety/ucm277114. htm. Accessed December 1, 2011.

2. Activated protein C (Xigris) for severe sepsis. Med Lett Drugs Ther 2002; 44:17.

3. E Abraham et al. Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. N Engl J Med 2005; 353:1332.

4. KM Rowan et al. Drotrecogin alfa (activated): real-life use and outcomes for the UK. Crit Care 2008; 12:R58.

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Drotrecogin alfa (activated) (Xigris - Lilly), recombinant human activated protein C, has been approved by the FDA for treatment, in combination with standard therapy, of critically ill adults with severe sepsis and a high risk of death.