REG - AstraZeneca PLC - Ondexxya approved in Japan for FXai reversal

AstraZenecaAnnouncement

29/03/2022 07:00

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RNS Number : 3123G  AstraZeneca PLC  29 March 2022

29 March 2022 07:00 BST

Ondexxya approved in Japan for reversal of acute major bleeds in patients on
Factor Xa inhibitors

Ondexxya is the first approved reversal agent specifically for Factor Xa
inhibitors, providing a major advance in the treatment of
patients hospitalised with life-threatening bleeding

 

Ondexxya (andexanet alfa) has been approved in
Japan for patients treated with the Factor Xa
(FXa) inhibitors apixaban, rivaroxaban or edoxaban, when reversal of
anticoagulation is needed due to life-threatening or uncontrolled bleeding.

 

The approval by the Japanese Ministry of Health, Labour and Welfare was
based on positive results from the  ANNEXA-4  Phase III clinical
trial showing Ondexxya rapidly and markedly reversed anti-FXa activity in
patients with acute major bleeding.

 

Ondexxya is the first approved medicine in Japan to specifically
reverse the anticoagulant effect of FXa
inhibitors apixaban, rivaroxaban or edoxaban in patients experiencing a
life-threatening or uncontrolled bleed. Japan is also the first country to
provide full regulatory approval of Ondexxya for use with all three of the FXa
inhibitors currently available. FXa inhibitors are increasingly used for the
prevention and treatment of thrombotic events, including deep vein
thrombosis and pulmonary embolism, or in patients at high risk of a stroke due
to an irregular heart rate (atrial fibrillation). While they prevent
unwanted clots from forming, they can also increase the risk of major
bleeding, which can be life-threatening.(1,2)

 

Masahiro Yasaka, MD, PhD, National Hospital Organisation Kyushu Medical
Centre, Fukuoka, Japan, said: "FXa inhibitors are essential
medicines for people prone to developing blood clots, but they
can also present a risk of uncontrolled bleeding and related complications,
which can be fatal if left untreated. Ondexxya's rapid reversal of the
anticoagulating effects of apixaban, rivaroxaban and edoxaban effectively
reduces the bleeding and is a major advancement in patient care."

 

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D,
AstraZeneca, said: "With the approval of Ondexxya in Japan, we are working to
make this important medicine available as quickly as possible for the small
proportion of patients with life-threatening or uncontrolled bleeding who
are on FXa inhibitors and who have not previously had an approved reversal
agent treatment option."

 

Ondexxya received approval by the US Food and Drug Administration under the
accelerated approval pathway in May 2018 and conditional approval by the
European Commission in April 2019 for adults treated with FXa inhibitors
apixaban and rivaroxaban. In the US, Ondexxya is marketed under the trade name
Andexxa [coagulation factor Xa (recombinant), inactivated-zhzo].

 

Notes

 

Life-threatening bleeding

There is an urgent need for a specific reversal agent for patients treated
with FXa inhibitors hospitalised with a major bleed. Millions of patients
worldwide depend on FXa inhibitors every day to prevent harmful blood clots
from forming;(3) however, these agents increase the risk of major
bleeding.(1,2) Major bleeding can be very serious and life-threatening, and
can happen inside the body and may not be visible. As prescriptions for FXa
inhibitors increase, the potential for serious bleeding hospital admissions
grows.(4,5)

 

ANNEXA-4

The approval of Ondexxya is supported by data from the ANNEXA-4 Phase III
trial, which evaluated the haemostatic efficacy  and
safety of Ondexxya in patients receiving a FXa inhibitor who were
experiencing an acute major bleed.(6 )In the trial, Ondexxya markedly
reversed anti-FXa activity within minutes, with 80% of patients
having excellent or good haemostatic efficacy sustained at 12
hours following administration. During the trial, 10.4% of patients
experienced at least one thrombotic event, the majority of which occurred in
patients who delayed or did not restart anticoagulation during the follow-up
period.(6 )Consistent with previous trial results in patients who are at
increased risk of thrombosis, 15.7% of patients died during the trial.(6)

 

Ondexxya

Ondexxya (andexanet alfa) is a recombinant protein specifically designed to
bind to FXa inhibitors and rapidly reverse their anticoagulant
effect. Ondexxya is a modified form of the human FXa molecule, an enzyme
that helps blood clot. Ondexxya works by acting as a decoy for oral and
injectable FXa inhibitors, which target and bind to FXa, allowing them to
exert their anticoagulant effect. When Ondexxya is given through an
intravenous infusion to a patient with FXa inhibitor-related bleeding, it
binds with high affinity to the FXa inhibitor, prevents it from inhibiting
the activity of FXa and reverses the anticoagulant effects of the
inhibitor.

 

AstraZeneca in CVRM

Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms
one of AstraZeneca's three disease areas and is a key growth driver for the
Company. By following the science to understand more clearly the underlying
links between the heart, kidneys and pancreas, AstraZeneca is investing in a
portfolio of medicines for organ protection and improving outcomes by slowing
disease progression, reducing risks and tackling co-morbidities. The Company's
ambition is to modify or halt the natural course of CVRM diseases and
potentially regenerate organs and restore function, by continuing to deliver
transformative science that improves treatment practices and CV health for
millions of patients worldwide.

 

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical
company that focuses on the discovery, development, and commercialisation of
prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals,
including Cardiovascular, Renal & Metabolism, and Respiratory &
Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries
and its innovative medicines are used by millions of patients worldwide.
Please visit astrazeneca.com (http://www.astrazeneca.com/)  and follow the
Company on Twitter @AstraZeneca (https://twitter.com/AstraZeneca) .

 

Contacts
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(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
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.

 

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. Eur
Heart J 2014;35:1873-1880.

3.   Coleman CI, et al. Real-world management of oral factor Xa
inhibitor-related bleeds with reversal or replacement agents including
andexanet alfa and four-factor prothrombin complex concentrate: a multicenter
study. Future Cardiol. 2021;17:127-135.

4.   Budnitz DS, et al. US Emergency Department Visits Attributed to
Medication Harms, 2017-2019. JAMA. 2021;326:1299-1309.

5.   Geller AL, et al. Emergency Visits for Oral Anticoagulant Bleeding. J
Gen Intern Med. 2020;35(1):371-373.

6.   Presentation: Milling T, Middeldorp S, Xu L, et al. Final Study Report
of Andexanet Alfa for Bleeding with Factor XA Inhibitors. Poster presented at
2021 European Stroke Conference; September 2021; Virtual.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

 

 

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