Date: 2014-11-18
Type of
information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the American Heart Association\'s Scientific Sessions 2014
Company: Boehringer Ingelheim (Germany)
Product: idarucizumab
Action
mechanism:
- monoclonal antibody. Idarucizumab is a humanized antibody fragment, or Fb, being investigated as a specific antidote for the anticoagulant effect of dabigatran. Pre-clinical studies indicate idarucizumab binds specifically to and inhibits dabigatran. In June 2014, the FDA granted Breakthrough Therapy Designation to idarucizumab.
Disease: rapid reversal of dabigatran-induced anticoagulation
Therapeutic
area: Cardiovascular diseases - Hematological diseases
Country: Australia, Austria, Belgium, Canada, Czech Republic, Estonia, Finland, France, Germany, Hong Kong, Ireland, Italy, Latvia, Netherlands, New Zealand, Portugal, Russian Federation, Slovakia, South Africa, Spain, Sweden, UK
Trial
details:
- The trial aims to evaluate the reversal of the anticoagulant effects of dabigatran by IV administration of 5.0g idarucizumab in patients treated with dabigatran etexilate who have uncontrolled bleeding or require emergency surgery or procedures. (NCT02104947)
Latest
news:
- • On November 18, 2014, Boehringer Ingelheim announced phase I study sub-analyses showing that its investigational antidote idarucizumab reverses the effects of dabigatran, the active ingredient in Pradaxa® (dabigatran etexilate mesylate), on fibrin formation in healthy volunteers. The results showed idarucizumab, a humanized antibody fragment (Fab), restores wound-site formation of fibrin, the main component of a blood clot. The findings were presented during the American Heart Association's Scientific Sessions 2014. In this sub-study of 35 healthy volunteers, fibrin formation was assessed after a small scratch, similar to a paper cut, was made. Measurements were conducted at baseline, after administration of Pradaxa®, and after subsequent administration of idarucizumab or placebo.
- The results showed that dabigatran almost completely inhibited the production of fibrinopeptide A (FPA), the marker of fibrin formation at the wound site, and that idarucizumab restored FPA production: At baseline, before the volunteers took Pradaxa®, the average level of FPA was 3981 ng/mL. On day three, 2.5 hours after the volunteers took Pradaxa®, the average level of FPA was 208 ng/mL, an approximate 95 percent decrease compared to baseline. On day four, 2.5 hours after the volunteers took Pradaxa® and 30 minutes after they were infused with 1 g, 2 g or 4 g of idarucizumab, FPA levels were 24 percent, 45 percent and 95 percent, respectively, of the average baseline level. The restored fibrin production at the wound site after idarucizumab dosing with 2 g or 4 g also correlated with reversal of the dabigatran-anticoagulation activity in circulating blood.
- Boehringer Ingelheim is continuing to evaluate idarucizumab in RE-VERSE AD™, a phase III global study investigating idarucizumab in actual clinical settings where PRADAXA patients may require emergency intervention or experience an uncontrolled or life threatening bleeding event. This is the first-ever trial to investigate a specific antidote in patients actively being treated with a newer oral anticoagulant.
- • On May 22, 2014, Boehringer Ingelheim announced the next step in the clinical development of idarucizumab, the investigational antidote for rapid reversal of dabigatran-induced anticoagulation. The specific antidote has already demonstrated immediate, complete and sustained reversal of the anticoagulant effect of dabigatran in healthy volunteers. Now the potential antidote will be investigated in the clinical setting in patients taking Pradaxa® (dabigatran etexilate).This is the first time that an antidote under development for a novel oral anticoagulant is investigated in a study in patients. Emergency rooms in more than 35 countries worldwide will participate in this study. Physicians will be equipped with the investigational antidote idarucizumab as a ‘ready to use’ solution for infusion. The first study sites in Europe have been initiated, and more sites and countries will follow during the course of the year.
- Prior clinical research of the antidote in a healthy volunteer study with 145 participants has already demonstrated the potential of the antidote for immediate, complete and sustained reversal of the anticoagulant effect of dabigatran. In the placebo-controlled study, the antidote was well tolerated and did not cause any clinically relevant side effects. Importantly, no pro-thrombotic effect was observed after the administration of the antidote and also no return of anticoagulant activity of dabigatran over time at adequate doses. These two aspects are especially valuable in clinical situations where rapid reversal of dabigatran-induced anticoagulation may be beneficial for patients taking Pradaxa®.
Is
general: Yes
