Xigris (drotrecogin alfa): withdrawal & recall

Prescription medicine used in hospital intensive care units for the treatment of adult patients with severe sepsis

26 October 2011

The Therapeutic Goods Administration (TGA) advises that Xigris (drotrecogin alfa) is currently being withdrawn from the worldwide market and consequently the units supplied in Australia are being recalled.

This voluntary action is being undertaken by Eli Lilly Australia Pty Ltd, the Australian sponsor of Xigris, following consultation with the Therapeutic Goods Administration (TGA) based on new evidence that the drug does not improve survival rates in patients treated for severe sepsis and is not based on safety concerns.

The products being withdrawn from the Australian market are:

  • XIGRIS drotrecogin alfa (activated) rhu 5mg powder for injection vial, Australian Register of Therapeutic Goods (ARTG) 78116
  • XIGRIS drotrecogin alfa (activated) rhu 20mg powder for injection vial, ARTG 78117 (Eli Lilly have informed that the 20 mg presentation is not marketed in Australia)

Information for health professionals

  • The sponsor is advising health professionals that patients currently receiving treatment with Xigris should have the treatment discontinued and Xigris treatment should not be initiated for new patients.
  • The mainstay of medical management in these patients is antibiotics and supportive therapy in an intensive care unit (ICU).
  • Eli Lilly is taking action due to the lack of efficacy seen in a recent clinical trial known as the PROWESS-SHOCK study, which showed no 28-day survival benefit of Xigris in septic shock patients. This means there is no advantage to patients from this medication over and above the high standard of medical care provided to patients with this condition in ICUs in Australia.
  • The TGA is working on this withdrawal/recall with Eli Lilly Australia, who is in the process of notifying wholesalers, hospital pharmacists and ICU physicians.

Additional information

  • Xigris (drotrecogin alfa) is a recombinant form of human Activated Protein C which is administered by intravenous infusion.
  • Severe sepsis can develop as a complication of common illnesses such as pneumonia and bacterial infections. It is characterised by an overwhelming systemic response to infection which can rapidly lead to organ failure and ultimately death.
  • Xigris was approved in Australia in 2002 for treatment of adult patients with severe sepsis (sepsis associated with acute organ dysfunction) who have high risk of death, based on results of the PROWESS study in which Xigris showed significant improvement in 28-day all-cause mortality.
  • Several subsequent studies have failed to confirm efficacy in related populations. These inconsistent efficacy outcomes may relate to differences in supportive therapy and ICU care across geographical areas.
  • The mortality rate in placebo-treated patients in the PROWESS-SHOCK study was considerably lower than predicted. This finding supports the suggestion that improvements in the standard of care over the past 10 years may explain the differences in outcomes between the PROWESS and the PROWESS-SHOCK studies.