Eli Lilly and Company announced that the European Committee for Proprietary Medicinal Products (CPMP) has issued a positive opinion for drotrecogin alfa (activated) [brand name Xigris] for the treatment of adult patients with severe sepsis with multiple organ failure when added to best standard care.
The CPMP has recommended to the European Commission that the approval should be granted under exceptional circumstances. For Xigris, this means Lilly and the CPMP must agree upon post-approval clinical trial commitments, including an obligation for Lilly to provide an annual update to the agency regarding its trials.
Sepsis is a syndrome characterized by an overwhelming systemic response to infection, which can rapidly lead to organ dysfunction and ultimately death. It can be triggered by a bacterial, viral, parasitic or fungal infection, often the result of events such as trauma, surgery, and burns or illnesses such as cancer and pneumonia. Sepsis may cause multiple organs in the body to fail and may trigger the onset of both abnormal clotting and bleeding. Every day 1,400 people worldwide die from severe sepsis, and it takes the lives of one in three of its victims within a month of diagnosis. In the European Union (EU), according to London-based Medtap International, severe sepsis and septic shock could be associated with the loss of up to 146,000 lives every year and as much as EUR 7.6 billion (U.S. $6.7 billion) in patient health care costs.
"We are pleased by the CPMP's positive opinion on drotrecogin alfa (activated) in Europe for patients with severe sepsis," said Richard Pilnik, president of European operations for Lilly. "In Europe, severe sepsis is associated with deaths on a similar scale to lung cancer, breast cancer or colon cancer every year, and there is currently no proven therapy to reduce mortality from this devastating syndrome."
Xigris was granted approval by the U.S. Food and Drug Administration on November 21, 2001. Since the U.S. approval, Xigris has been approved in Israel, Argentina, Mexico, Australia, Columbia, Romania and Peru. When approved in Europe, Xigris will be the first proven therapy to reduce mortality from severe sepsis, a devastating syndrome characterized by an overwhelming systemic response to infection, which can rapidly lead to organ dysfunction and ultimately death.
The CPMP, comprised of regulators from 15-member countries, based its positive opinion on the results of an international Phase III clinical trial (known as PROWESS, Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis), which were published March 8, 2001, in The New England Journal of Medicine. Drotrecogin alfa (activated) reduced the relative risk of death from severe sepsis by nearly 20 percent in the trial involving 1,690 patients who had sepsis with at least one associated organ dysfunction.
Bleeding events are common in patients with severe sepsis. In PROWESS, bleeding was the most common adverse reaction associated with drotrecogin alfa (activated) therapy. Serious bleeding events were observed during the 28-day study period in 3.5 percent of drotrecogin alfa (activated)-treated and 2.0 percent of placebo-treated patients. The difference in serious bleeding occurred primarily during the infusion period. Intracranial hemorrhage (ICH) may occur in patients with severe sepsis.
In PROWESS, the incidence of intracranial hemorrhage was 0.2 percent for drotrecogin alfa (activated)-treated patients and 0.1 percent for placebo-treated patients. The incidence of ICH in non-placebo-controlled trials has been reported as approximately 0.9 percent during the infusion period. The risk of ICH may be increased in patients with risk factors for bleeding such as severe coagulopathy and severe thrombocytopenia.