Xigris has received FDA approval for increasing survival in high-risk adult patients with severe sepsis.

Xigris ( Drotrecogin alfa, activated ) is a recombinant version of human Activated Protein C, which modulates microvascular function by decreasing inflammation and coagulation and increasing fibrinolysis.

Eli Lilly and FDA notified healthcare professionals about revisions to the WARNINGS section of labeling for Xigris.

The warning is based upon exploratory analyses of the ADDRESS clinical trial database and subsequent reanalysis of the PROWESS ( Phase 3 registration ) clinical trial database.

This new warning applies only to patients with single organ dysfunction and recent surgery. These patients may not be at high risk of death and therefore may not be indicated for Xigris.
Among the small number of patients enrolled in PROWESS with single organ dysfunction and recent surgery ( surgery within 30 days prior to study treatment ) all-cause mortality was numerically higher in the Xigris group ( 28-day: 10/49; in-hospital: 14/48 ) compared to the placebo group ( 28-day: 8/49; in-hospital: 8/47 ).

In a preliminary analysis of the subset of patients with single organ dysfunction and recent surgery from a separate, randomized, placebo-controlled study ( ADDRESS ) of septic patients at lower risk of death ( APACHE II score <25 or single sepsis-induced organ failure at any APACHE II score ) all-cause mortality was also higher in the Xigris group ( 28-day: 67/323; in-hospital: 76/325 ) compared to the placebo group ( 28-day: 44/313; in-hospital: 62/314 ).

Patients with single organ dysfunction and recent surgery may not be at high risk of death irrespective of APACHE II score and therefore may not be among the indicated population. Xigris should be used in these patients only after careful consideration of the risks and benefits.

Source : FDA, 2005


XagenaMedicine2005