Drotrecogin alfa

Activated human protein C

B01AD10

Antithrombotic

Template: Infobox chemical / molecular formula search available

Drotrecogin (trade name: Xigris ®, manufactured by Lilly) is a recombinant form of the naturally occurring in blood plasma activated protein C, from which it differs only by unique oligosaccharides in the carbohydrate portion of the molecule. Drotrecogin is one of the serine proteases. It was meant in intensive care in adults in the case of severe sepsis with multiple organ failure when added to best standard care. The drug was taken off the market in 2011 after the initial positive benefit -risk assessment could not be maintained.

Drotrecogin is produced by genetic engineering from an established human cell line. It differs from the naturally present in plasma-derived activated protein C by single to this protein -bound oligosaccharides.

Mechanism of Action

The properties of drotrecogin are comparable to those of endogenous human activated protein C. The body's protein has an antithrombotic effect by blocking factors Va and VIIIa. By inhibition of PAI -1 of the active ingredient promotes fibrinolysis. Activated protein C suppressed also the release of the proinflammatory cytokines interleukin -1 and TNF - α.

Withdrawal

Xigris in 2002 authorized under " exceptional circumstances ". One such method is applied when the applicant can demonstrate that it is not possible to present comprehensive data on the efficacy and safety of the drug, either due to the rarity of the disease, limited scientific knowledge in the field of use or ethical considerations involved. The present results at the time of the PROWESS (Protein C Worldwide Evaluation in Severe Sepsis ) showed a significant improvement in 28-day all-cause mortality. The study of 1,690 patients with severe sepsis was subsequently terminated prematurely, the authorization was granted on the condition for annual revaluation. 2007 was the EMA that subsequent studies, the efficacy found in the pivotal study, PROWESS could not reproduce and requested further clinical data.

A study published in April 2011 Cochrane analysis showed that no significant survival benefit for patients with sepsis was demonstrated by treatment with drotrecogin in another five randomized clinical trials.

After 2011, the results of a study on the treatment of septic shock ( PROWESS -SHOCK trial ) missed the endpoints, the positive benefit - risk ratio for drotrecogin was in jeopardy. The manufacturer Eli Lilly announced in October 2011, the global setting of the sale of the drug.