Type of information: Negative opinion for the granting of a Market Authorisation in the EU
- anticoagulant agent/oral direct Factor Xa inhibitor . Betrixaban is an oral, once-daily Factor Xa inhibitor anticoagulant. It is an FDA-designated Fast Track therapy for extended-duration VTE prophylaxis in acute medically ill patients.
Company: Portola Pharmaceuticals (USA - CA)
Disease: prevention of venous thromboembolism (VTE) in adult patients hospitalized for an acute medical illness with risk factors for VTE
- • On February 20, 2018, Portola Pharmaceuticals announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has communicated a negative trend vote for betrixaban, an oral, once-daily Factor Xa inhibitor, for the prevention of venous thromboembolism (VTE) in adult patients hospitalized for an acute medical illness with risk factors for VTE. A negative trend vote means it is unlikely that the CHMP will adopt a positive opinion on the Company's MAA at the formal CHMP decision vote scheduled for March 2018 , and that additional steps would be needed to gain marketing approval in Europe .
- The CHMP's position is that betrixaban efficacy is acknowledged in the APEX trial, but uncertainties remain regarding a positive benefit risk, which is not supported by a second confirmatory study, biological plausibility for betrixaban in another approved indication or external support within the class from other Factor Xa inhibitors, which are not approved for the acute medically ill population.
- • On December 12, 2017, Portola Pharmaceuticals announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has requested additional information related to the Marketing Authorization Application (MAA) for betrixaban. The MAA for betrixaban includes data from Portola's pivotal Phase 3 APEX Study, which enrolled 7,513 patients at more than 450 clinical sites worldwide. The APEX study evaluated oral betrixaban for 35 to 42 days compared with injectable enoxaparin for 6 to 14 days followed by placebo in assessing the prevention of venous thromboembolism (VTE) in high-risk acutely ill medical patients.
- Results from the APEX Study have been peer-reviewed and published in The New England Journal of Medicine, Circulation and the American Heart Journal.
- • On November 21, 2017, Portola Pharmaceuticals announced that the FDA has extended the review period for the Company's Prior Approval Supplement (PAS) for Bevyxxa® (betrixaban) to allow the agency time to review the entire submission. The FDA informed the company that it will respond to the PAS request to change the current manufacturing release specification within the standard 60-day extension period. No additional information was requested at this time. The new action date is January 30, 2018 .
- • On June 23, 2017, Portola Pharmaceuticals announced the FDA has approved Bevyxxa® (betrixaban), the first and only anticoagulant for hospital and extended duration prophylaxis (35 to 42 days) of venous thromboembolism (VTE) in adult patients hospitalized for an acute medical illness who are at risk for thromboembolic complications due to moderate or severe restricted mobility and other risk factors for VTE.
- Bevyxxa® was granted a Fast Track designation and approved by the FDA under Priority Review, which is a status given to drugs that may offer significant improvements in treatment or provide a treatment where no adequate therapy exists. Bevyxxa® has been approved based on data from Portola's pivotal Phase 3 APEX Study, which enrolled 7,513 patients at more than 450 clinical sites worldwide.
- The APEX study evaluated oral betrixaban for 35 to 42 days compared with injectable enoxaparin for 6 to 14 days followed by placebo in assessing the prevention of VTE in high-risk acutely ill medical patients. As detailed in the prescribing information, Bevyxxa efficacy was measured in the modified Intent-to-Treat (mITT) analysis, which includes 7,441 patients assessed by a composite outcome score comprising either the occurrence of asymptomatic proximal DVT or symptomatic DVT, non-fatal PE or VTE-related death. Bevyxxa reduced the incidence of DVT and PE blood clots compared with those taking enoxaparin plus placebo (4.4 percent vs. 6.0 percent; relative risk 0.75, 95 percent CI: 0.61, 0.91) with no significant increase in major bleeding (0.67 percent vs. 0.57 percent). The most frequent reason for treatment discontinuation was bleeding, with an incidence rate for all bleeding episodes of 2.4 percent and 1.2 percent for betrixaban and enoxaparin, respectively.
- In the EU, the European Medicines Agency’s Committee for Human Medicinal Products (CHMP) is reviewing the Marketing Authorization Application for betrixaban under its standard review period.
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: 2017-06-23
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: