– Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced that the Scottish Medicines Consortium (SMC) has accepted ONDEXXYA®▼ (andexanet alfa) for use within NHS Scotland in adults treated with the direct Factor Xa (FXa) inhibitors apixaban or rivaroxaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding, on an interim basis subject to ongoing evaluation and future reassessment.
“As the number of patients on direct Fxa inhibitors continues to increase, so does the need to ensure
we can protect patients who may experience life-threatening or uncontrolled bleeds,” said Professor
Henry Watson, Consultant Haematologist, University of Aberdeen. “Andexanet alfa will give clinicians
an approved therapy option and clinical strategy for the reversal of major bleeding in patients being
treated with rivaroxaban and apixaban. This is a positive step forward for the safety of patients being
treated with these important and widely used drugs.”
Direct FXas inhibitors are increasingly used for the prevention and treatment of thrombotic events,
such as deep vein thrombosis and pulmonary embolism, or if a patient is at high risk of a stroke due
to an irregular heart rate (atrial fibrillation). These direct FXa inhibitors stop the blood from clotting
normally in order to prevent unwanted clots from forming, but in doing so, can also increase the risk of
major bleeding which can be life-threatening.
1,2 Until now, there has been no licensed therapy to reverse direct-FXa-activity in the patients who experience these life-threatening bleeds. Andexanet alfa can neutralise the anticoagulant effect of apixaban and rivaroxaban, thus stopping the life-threatening bleed.
“Andexanet alfa is now available to patients in Scotland to reverse life-threatening and uncontrolled
bleeds as a result of treatment with the direct FXas inhibitors apixaban or rivaroxaban,” said Sean
Richardson, Vice President and General Manager for Alexion UK & Ireland. “We are pleased to serve
all patients in Scotland who could benefit from andexanet alfa in this area of critical need.”
Data was provided from two Phase 3 ANNEXA studies (ANNEXA-R and ANNEXA-A) that evaluated the
safety and efficacy of andexanet alfa in reversing the anticoagulant activity of rivaroxaban or apixaban
in older subjects, and data from the Phase 3b/4 ANNEXA-4 study that evaluated efficacy and safety in
approximately 350 patients with life-threatening or uncontrolled major bleeding associated with the
use of a direct Fxa inhibitors. In these patients, treatment with andexanet alfa markedly reduced the
anti-factor Xa activity of apixaban and rivaroxaban, reversing the anticoagulant effect. 82 percent of
efficacy evaluable bleeding patients had good hemostatic efficacy (stopping of bleeding) at 12 hours
when compared to baseline when adjudicated according to pre-specified criteria.3
The most frequently reported adverse reactions in subjects administered andexanet alfa were mild or
moderate infusion-related reactions. Very common infusion related reactions included flushing and
feeling hot. Commonly observed infusion related- reactions include cough, dysgeusia and dyspnoea.
Transient elevations of pro-coagulant markers D-dimer and F1+2 fragments were also very commonly
observed in subjects. Amongst bleeding patients administered andexanet alfa, commonly reported
side effects were ischaemic stroke and pyrexia, with uncommonly reported side effects of cerebral
infarction, cerebrovascular accident, transient ischaemic attack, acute myocardial infarction, cardiac
arrest, myocardial infarction, deep vein thrombosis, iliac artery occlusion and pulmonary embolism.
4
The European Commission (EC) granted conditional Marketing Authorisation for andexanet alfa in
Europe in April 2019.4 Marketed in the US as ANDEXXA® [coagulation factor Xa (recombinant),
inactivated-zhzo], it was approved by the U.S. Food and Drug Administration (FDA) in May 2018 under
the FDA’s Accelerated Approval pathway.5
Andexanet alfa was developed and launched by Portola Pharmaceuticals. In July 2020, Portola
Pharmaceutical was acquired by Alexion. Andexanet alfa is now owned and marketed by Alexion.6
References:
1. Held C, Hylek EM, Alexander JH, et al. Clinical outcomes and management associated with major bleeding in patients
with atrial fibrillation treated with apixaban or warfarin: insights from the ARISTOTLE trial. Eur Heart J 2015;36:1264-
1272.
2. Piccini JP et al. Management of major bleeding events in patients treated with rivaroxaban vs. warfarin: results from
the ROCKET AF trial. European Heart Journal 2014;35:1873–1880.
3. Connolly S.J et al. Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors. N Engl J Med.
2019. 380. 10.1056/NEJMoa1814051. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa1814051
4. European Medicines Agency – Ondexxya. Date accessed: August 2020. Available here:
https://www.ema.europa.eu/en/medicines/human/EPAR/ondexxya
5. Food and Drug Administration – ANDEXXA (coagulation factor Xa (recombinant), inactivated-zhzo). Date accessed
August 2020. Available here: https://www.fda.gov/media/113285/download
6. Alexion Complete Acquisition of Portola. August 2020. Date accessed: August 2020. Available here:
https://www.businesswire.com/news/home/20200702005276/en/Alexion-Completes-Acquisition-Portola