Drotrecogin alfa (activated)...a sad final fizzle to a roller-coaster party

Crit Care. 2012 Feb 6;16(1):107. doi: 10.1186/cc11152.


Following the failure of PROWESS-SHOCK to demonstrate efficacy, Eli Lilly and Company withdrew drotrecogin alfa (activated) from the worldwide market. Drotrecogin was initially approved after the original trial, PROWESS, was stopped early for overwhelming efficacy. These events prompt consideration of both the initial approval decision and the later decision to withdraw. It is regrettable that the initial decision was made largely on a single trial that was stopped early. However, the decision to approve was within the bounds of normal regulatory practice and was made by many approval bodies around the world. Furthermore, the overall withdrawal rate of approved drugs remains very low. The decision to withdraw was a voluntary decision by Eli Lilly and Company and likely reflected key business considerations. Drotrecogin does have important biologic effects, and it is probable that we do not know how best to select patients who would benefit. Overall, there may still be a small advantage to drotrecogin alfa, even used non-selectively, but the costs of determining such an effect with adequate certainty are likely prohibitive, and the point is now moot. In the future, we should consider ways to make clinical trials easier and quicker so that more information can be available in a timely manner when considering regulatory approval. At the same time, more sophisticated selection of patients seems key if we are to most wisely test agents designed to manipulate the septic host response.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Infective Agents / adverse effects
  • Anti-Infective Agents / economics
  • Anti-Infective Agents / therapeutic use
  • Drug Approval / economics
  • Drug Approval / methods
  • Drug Industry / economics
  • Drug Industry / methods*
  • Drug Industry / standards
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / economics
  • Fibrinolytic Agents / therapeutic use
  • Humans
  • Protein C / adverse effects
  • Protein C / economics
  • Protein C / therapeutic use*
  • Randomized Controlled Trials as Topic / economics
  • Randomized Controlled Trials as Topic / standards
  • Randomized Controlled Trials as Topic / trends
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / economics
  • Recombinant Proteins / therapeutic use
  • Risk Assessment / economics
  • Risk Assessment / methods
  • Risk Assessment / standards
  • Safety-Based Drug Withdrawals / economics
  • Safety-Based Drug Withdrawals / methods*
  • Sepsis / drug therapy
  • Sepsis / economics


  • Anti-Infective Agents
  • Fibrinolytic Agents
  • Protein C
  • Recombinant Proteins
  • drotrecogin alfa activated