Date: 2015-11-20
Type of information: Granting of a Market Authorisation in the EU
Product name: Praxbind®
Compound: idarucizumab
Therapeutic area: Cardiovascular diseases - Hematologic diseases
Action mechanism: monoclonal antibody. Idarucizumab is a fully humanized antibody fragment, or Fab, being investigated as a specific antidote for Pradaxa®. Pre-clinical studies indicate idarucizumab binds specifically to and inhibits dabigatran with no other expected interactions.
Company: Boehringer Ingelheim (Germany)
Disease: specific antidote for Pradaxa® - reversion of the anticoagulant effect of dabigatran due to uncontrolled life-threatening bleeding requiring urgent intervention or a need to undergo an emergency surgery/urgent invasive procedure.
Latest news: * On October 16, 2015, the FDA granted accelerated approval to Praxbind® (idarucizumab) for use in patients who are taking the anticoagulant Pradaxa® (dabigatran) during emergency situations when there is a need to reverse Pradaxa’s blood-thinning effects. The FDA approved Pradaxa® in 2010 to prevent stroke and systemic blood clots in patients with atrial fibrillation, as well as for the treatment and prevention of deep venous thrombosis and pulmonary embolism. Praxbind® is the first reversal agent approved specifically for Pradaxa® and works by binding to the drug compound to neutralize its effect. Praxbind® solution is for intravenous injection. The safety and effectiveness of Praxbind® were studied in three trials involving a total of 283 healthy volunteers taking Pradaxa (i.e., people who did not require an anticoagulant). In the healthy volunteers who were given Praxbind®, there was an immediate reduction in the amount of Pradaxa® in participants’ blood (measured as unbound dabigatran plasma concentration) that lasted for a period of at least 24 hours. In this study, the most common side effect from use of Praxbind® was headache. Another trial included 123 patients taking Pradaxa® who received Praxbind® due to uncontrolled bleeding or because they required emergency surgery. In this ongoing trial, based on laboratory testing, the anticoagulant effect of Pradaxa® was fully reversed in 89 percent of patients within four hours of receiving Praxbind®. In this patient trial, the most common side effects were low potassium (hypokalemia), confusion, constipation, fever and pneumonia. Reversing the effect of Pradaxa® exposes patients to the risk of blood clots and stroke from their underlying disease (such as atrial fibrillation). The Praxbind® labeling recommends patients resume their anticoagulant therapy as soon as medically appropriate, as determined by their health care provider. * On September 24, 2015, the Committee for Medicinal Products for Human Use (CHMP) has recommended granting a marketing authorisation, under accelerated assessment, for Praxbind® (idarucizumab) as a specific antidote to the anticoagulant medicine Pradaxa (dabigatran etexilate), when rapid reversal of its effect is required. Praxbind® is to be used when a patient taking Pradaxa needs to undergo an emergency surgery or when life-threatening or uncontrolled bleeding occurs. Praxbind® will be available as 2.5g/50 mL solution for injection/infusion. It is used when rapid reversal of dabigatran effect is required. * On May 28,2015, the FDA has granted orphan drug designation for idarucizumab to reverse the anticoagulant effect of dabigatran due to uncontrolled life-threatening bleeding requiring urgent intervention or a need to undergo an emergency surgery/urgent invasive procedure. * On April 23, 2015, Boehringer Ingelheim announced that the FDA has granted Priority Review to the Biologics License Application (BLA) for idarucizumab, which is being investigated to specifically reverse the anticoagulant effect of dabigatran, the active ingredient in Pradaxa® (dabigatran etexilate mesylate) in patients needing emergency intervention or experiencing an uncontrolled or life-threatening bleeding event. The idarucizumab BLA will be reviewed under Accelerated Approval and is the first review for a reversal agent in the novel oral anticoagulant (NOAC) class. Currently, no NOACs have an approved reversal agent. The application includes phase I data showing the potential for idarucizumab to provide immediate reversal of the anticoagulant effect of dabigatran. In these studies, no clinically relevant adverse events related to idarucizumab were observed. Additionally, no procoagulant effect was observed after the administration of idarucizumab when measured by coagulation assay. Interim data from the ongoing RE-VERSE AD™ trial, a phase III global study investigating idarucizumab in actual clinical settings, was also included in the application. * On March 2, 2015, Boehringer Ingelheim announced it has submitted a biologics license application (BLA) to the FDA, requesting an Accelerated Approval pathway, for the use of idarucizumab to reverse the anticoagulant effect of dabigatran, the active ingredient in Pradaxa® (dabigatran etexilate mesylate). The new application includes phase I data in volunteers showing that idarucizumab provided immediate, complete and sustained reversal of the anticoagulant effect of dabigatran. Phase I data in healthy volunteers demonstrated the potential of idarucizumab to achieve immediate, complete and sustained reversal of dabigatran-induced anticoagulation. In these placebo-controlled studies, idarucizumab did not cause any clinically relevant side effects. No pro-thrombotic effect was observed after the administration of idarucizumab and no return of anticoagulant activity of dabigatran was seen over time at adequate doses. Other phase I data in healthy volunteers show that idarucizumab restores wound-site formation of fibrin, the main component of a blood clot. Boehringer Ingelheim is continuing to evaluate idarucizumab in RE-VERSE AD™, a phase III global study investigating idarucizumab in actual clinical settings. This is the only trial to examine patients being treated with PRADAXA who are in need of emergency intervention or experience an uncontrolled or life-threatening bleeding event. * On June 26, 2014, Boehringer Ingelheim announced that the FDA has granted Breakthrough Therapy Designation to idarucizumab, an investigational fully humanized antibody fragment, or Fab, being studied as a specific antidote for Pradaxa® (dabigatran etexilate mesylate). Boehringer Ingelheim is planning to pursue an Accelerated Approval pathway for idarucizumab. Data from a phase I study presented at the American Heart Association Scientific Sessions in 2013 showed that idarucizumab was able to achieve immediate, complete and sustained reversal of dabigatran-induced anticoagulation in healthy humans. A global phase III study, RE-VERSE AD™, is underway in patients taking Pradaxa® who have uncontrolled bleeding or require emergency surgery or procedures. Currently, no U.S. sites have been initiated; however, European sites are actively enrolling.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2015-10-16
UE authorization: 2015-11-20
Favourable opinion UE: 2015-09-24
Favourable opinion USA:
Orphan status USA: 2015-05-28
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: OTC status: Other news:
