Portola Pharmaceuticals issued the following announcement on May 3.
Portola Pharmaceuticals, Inc.® (Nasdaq:PTLA) today announced that the U.S. Food and Drug Administration (FDA) has approved Andexxa® [coagulation factor Xa (recombinant), inactivated-zhzo], the first and only antidote indicated for patients treated with rivaroxaban and apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.
Andexxa received both U.S. Orphan Drug and FDA Breakthrough Therapy designations and was approved under the FDA's Accelerated Approval pathway based on the change from baseline in anti-Factor Xa activity in healthy volunteers. Continued approval for this indication may be contingent upon post-marketing study results to demonstrate an improvement in hemostasis in patients.
"Today's approval represents a significant step forward in patient care and one that the medical community has been eagerly anticipating," said Stuart J. Connolly, M.D., ANNEXA-4 Executive Committee chairman and professor in the Department of Medicine of the Faculty of Health Sciences at McMaster University in Hamilton, Ontario. "Andexxa's rapid reversal of the anticoagulating effects of rivaroxaban and apixaban will help clinicians treat life-threatening bleeds, where every minute counts."
The use of Factor Xa inhibitors is rapidly growing because of their efficacy and safety profile compared to enoxaparin and warfarin in preventing and treating thromboembolic conditions such as stroke, pulmonary embolism and venous thromboembolism (VTE). This growth has come with a related increase in the incidence of hospital admissions and deaths related to bleeding, the major complication of anticoagulation. In the U.S. alone in 2016, there were approximately 117,000 hospital admissions attributable to Factor Xa inhibitor-related bleeding and nearly 2,000 bleeding-related deaths per month.
"We are grateful to the patients who participated in our trials, our clinical trial collaborators, our employees and the FDA for their help in bringing this new drug to market for the benefit of patients with Factor Xa inhibitor-related bleeding," said Bill Lis, chief executive officer of Portola. "We are proud that Andexxa is a first-in-class medicine discovered in our labs. In addition to Bevyxxa, the first and only anticoagulant approved for extended VTE prevention in acute hospitalized medical patients, Andexxa is our second FDA-approved product with the potential to save lives and have a major impact on global public health. We remain committed to our scientific leadership in the fields of thrombosis and hematologic cancers."
The approval of Andexxa is supported by data from two Phase 3 ANNEXA studies (ANNEXA-R and ANNEXA-A) published in The New England Journal of Medicine, which evaluated the safety and efficacy of Andexxa in reversing the anticoagulant activity of the Factor Xa inhibitors rivaroxaban and apixaban in healthy volunteers (Figure 1 and Figure 2, respectively). As described in the label, results demonstrated that Andexxa rapidly and significantly reversed anti-Factor Xa activity (the anticoagulant mechanism of these medicines). The median decrease in anti-Factor Xa activity from baseline was 97 percent for rivaroxaban and 92 percent for apixaban.
Interim data from the ongoing ANNEXA-4 single-arm, open-label study in patients with major bleeding also were assessed by the FDA as part of its review and approval. Data from 185 evaluable patients showed that Andexxa rapidly and significantly reversed anti-Factor Xa activity when administered as a bolus and sustained this reversal when followed by a 120-minute infusion. The median decrease from baseline was 90 percent for rivaroxaban and 93 percent for apixaban.
For additional Important Safety Information and Andexxa's full Prescribing Information, please visit http://www.Andexxa.com.
The post-marketing requirement is a clinical trial that randomizes patients to receive either Andexxa or usual care (the type of care the enrolling institution would provide in the absence of Andexxa). This study is scheduled to be initiated in 2019 and be reported in 2023.
"The expansion of available reversal agents for people prescribed newer oral anticoagulant therapies is crucial," said Randy Fenninger, chief executive officer of the National Blood Clot Alliance, a patient-led, voluntary health advocacy organization. "The availability now of a reversal agent specific to rivaroxaban and apixaban expands choice and enables patients and providers to consider these treatment options with greater confidence."
Consistent with the Company's prior plan, Portola expects to launch Andexxa under an Early Supply Program with Generation 1 product in early June. Broader commercial launch is anticipated in early 2019 upon FDA approval of its Generation 2 manufacturing process.
The Marketing Authorization Application (MAA) for andexanet alfa is also under review by the European Medicines Agency. The Committee for Medicinal Products for Human Use (CHMP) communicated a positive trend vote on the MAA in February 2018. A formal opinion from the CHMP is expected by the end of 2018, and the European Commission is expected to issue a decision in early 2019.
Original source can be found here.