Other safety alerts
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| The United States: Update on the Safety of Andexxa: FDA Safety Communication |
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Summary of the Issue
Since approval, the United States Food and Drug Administration (FDA) has received postmarketing safety data on thromboembolic events, including serious and fatal outcomes, in patients treated with Andexxa (coagulation factor Xa (recombinant), inactivated-zhzo). Based on available data, the serious risks including the increase in thromboembolic events are such that the FDA considers the risks of the product to outweigh its benefits. The FDA has communicated this position to AstraZeneca, and the company has submitted a request to voluntarily withdraw the Biologic License Application (BLA) for the product for commercial reasons. Additionally, the company has confirmed that it will end U.S. commercial sales by December 22, 2025. Andexxa will no longer be manufactured for or sold in the U.S. by AstraZeneca after December 22, 2025.
Continuous monitoring and assessment of the safety of all biological products, including Andexxa, is an FDA priority, and we remain committed to informing the public when we learn new information about these products.
Background:
The FDA initially granted accelerated approval (AA) of Andexxa, a recombinant modified human factor Xa (FXa) protein, in 2018, indicated for patients treated with rivaroxaban or apixaban when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding. Initial approval included a Boxed Warning for thromboembolic risks. AA was granted based on the change from baseline in anti-activated FXa (anti-FXa) activity in healthy volunteers, as a surrogate endpoint reasonably likely to predict clinical benefit.
At the time of AA of Andexxa, AstraZeneca (Applicant) was subject to a requirement to conduct a randomized controlled trial (NCT03661528) to verify the clinical benefit of Andexxa among patients with intracerebral hemorrhage following treatment with rivaroxaban or apixaban. On January 31, 2024, the Applicant submitted a supplemental Biologics Licensing Application (sBLA) for Andexxa with the results of the ANNEXA-I trial to fulfill this requirement. The FDA convened a meeting of the Cellular, Tissue, and Gene Therapies Advisory Committee (AC) on November 21, 2024, to discuss the results of the ANNEXA-I trial. The major safety findings discussed at the AC meeting included a doubling of the rate of thromboses and thrombosis-related deaths at Day 30 in the Andexxa arm compared with usual care (UC):
• Increased risk of thrombosis: ANNEXA-I demonstrated an increased incidence of thrombosis (14.6% versus 6.9%) and thrombosis-related deaths at Day 30 (2.5% versus 0.9%) in the Andexxa arm compared with the UC arm, respectively.
• Of the 35 Andexxa patients who experienced a thrombotic event, 18 (53%) had their event earlier than those 1 of 16 patients (6.3%) in the usual care group.
• Death related to thrombotic events through 30 days occurred in 6 patients (2.5%) in the Andexxa arm compared with 2 patients (0.9%) in the usual care control arm.
The FDA will continue working with AstraZeneca to keep providers and the public informed as AstraZeneca prepares to end sale of Andexxa.
Please refer to the following website in FDA for details:
http://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/update-safety-andexxa
In Hong Kong, Andexxa Powder For Solution For Infusion 200mg (HK-68130) is a pharmaceutical product registered by Astrazeneca Hong Kong Limited (Astrazeneca) and is a prescription-only medicine. So far, the Department of Health (DH) has not received any adverse drug reaction report with regard to Andexxa. Arising from the FDA announcement, DH contacted Astrazeneca and the company confirmed that the product with expiry date in December 2025 has been distributed to only 1 public hospital and 4 private hospitals since its registration in February 2024. Besides, Astrazeneca will send notification letters to the aforesaid hospitals to advise their physicians on the safety update in the FDA announcement and to use Andexxa in line with assessed benefit–risk considerations. DH will continue to maintain contact with the company for any updated information and remain vigilant on safety update of the drug issued by other overseas drug regulatory authorities for consideration of any action deemed necessary and appropriate.
Ends/Friday, Dec 19, 2025
Issued at HKT 17:15
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