The recent first global approval of andexanet alfa [coagulation factor Xa (recombinant), inactivated-zhzo] has been reviewed in detail in the First Global Approval report in Adis’ journal Drugs[1], based on the development milestones tracked in AdisInsight[2].

Andexanet alfa (Andexxa ®), developed by Portola Pharmaceuticals  received its first global approval in  May 2018 in the USA for use in adults treated with rivaroxaban and apixaban, when reversal of its anticoagulant effects is required because of life-threatening or uncontrolled bleeding. The drug is a first-in-class recombinant modified factor Xa protein. It is administered intravenously as a universal antidote that reverses the anticoagulant effects of factor Xa direct and indirect inhibitors.[3]

Drugs used to treat or prevent thromboembolism and stroke during atrial fibrillation include apixaban, edoxaban, rivaroxaban and betrixaban as direct factor Xa inhibitors, and fondaparinux and enoxaparin as indirect inhibitors, are effective medicines, but there is a risk of bleeding complications with their use. Therefore, the availability of a andexanet alfa, a specific reversing agent, is of clinical benefit. [1]

Andexanet alfa was approved via the FDA Accelerated Approval pathway, and has been granted Orphan Drug and Breakthrough Therapy designations.[4]

The approval was supported by data from the ANNEXA-R[5] and ANNEXA-A[6] studies that demonstrated efficacy and safety of the agent against bleeding induced by rivaroxaban or apixaban in volunteers.   An additional FDA-requested study, ANNEXA-4, is underway in the US and cetain European counties. This phase IIIb/IV trial will investigate the use of andexanet alfa in patients receiving a factor Xa inhibitor who are experiencing an acute major bleed. [7]

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, explained that the approval was “a significant step forward in patient care and one that the medical community has been eagerly anticipating.” This is because, “Andexxa’s rapid reversal of the anticoagulating effects of rivaroxaban and apixaban will help  clinicians treat life-threatening bleeds, where every minute counts, “ he said. [4]

Andexanet alfa is also under regulatory review in the EU and phase III clinical investigation is underway in Canada. [2]

The prescribing information carries a black box warning against thromboembolic and ischemic risks, cardiac Arrest and sudden death.[8]

For further information related to the first approval of andexanet alfa please visit Drugs[1],  or to learn more about the overall development of each of the drugs mentioned across all indications visit AdisInsight.

Image credit:  Aron – Unsplash

Leave a Reply