FDA Determines Andexxa Risks Outweigh Benefits, AstraZeneca to Withdraw Anticoagulant Reversal Agent
核心洞察
The FDA concluded that Andexxa's serious thromboembolic risks outweigh its benefits, prompting AstraZeneca to voluntarily withdraw the drug and end U.S. sales by December 22, 2025.
The ANNEXA-I trial revealed a doubling of thrombosis (搜索) rates (14.6% vs 6.9%) and thrombosis-related deaths (2.5% vs 0.9%) at 30 days compared to usual care.
Andexxa, approved in 2018 for reversing rivaroxaban or apixaban anticoagulation during life-threatening bleeding, will no longer be manufactured or sold in the U.S.
The U.S. Food and Drug Administration has determined that the risks of Andexxa (coagulation factor Xa (搜索) (recombinant), inactivated-zhzo) outweigh its benefits, leading AstraZeneca to voluntarily withdraw the anticoagulant reversal agent from the American market. The company will cease U.S. commercial sales by December 22, 2025, and will no longer manufacture the drug for the U.S. market.
Critical Safety Findings Drive Withdrawal Decision
The FDA's decision stems from postmarketing safety data revealing serious thromboembolic events, including fatal outcomes, in patients treated with Andexxa. The agency communicated its position to AstraZeneca, which subsequently submitted a request to voluntarily withdraw the Biologic License Application for commercial reasons.
The pivotal ANNEXA-I trial (NCT03661528), designed to verify clinical benefit among patients with intracerebral hemorrhage (搜索) following rivaroxaban or apixaban treatment, demonstrated alarming safety signals. Results presented to the FDA's Cellular, Tissue, and Gene Therapies Advisory Committee on November 21, 2024, showed a doubling of thrombosis (搜索) rates and thrombosis-related deaths at 30 days in the Andexxa arm compared with usual care.
ANNEXA-I Trial Results Reveal Significant Safety Concerns
The randomized controlled trial revealed several concerning safety findings:
- Increased thrombosis risk: The Andexxa group experienced thrombosis at a rate of 14.6% versus 6.9% in the usual care group
- Higher mortality: Thrombosis-related deaths occurred in 2.5% of Andexxa patients compared to 0.9% in the usual care arm at 30 days
- Earlier onset of events: Among 35 Andexxa patients who experienced thrombotic events, 18 (53%) had events occur earlier than the single patient (6.3%) in the usual care group who experienced such events
- Fatal outcomes: Six patients (2.5%) in the Andexxa arm died from thrombosis-related events within 30 days, compared to two patients (0.9%) in the usual care control arm
Background and Regulatory History
Andexxa received FDA accelerated approval in 2018 as a recombinant modified human factor Xa (搜索) protein indicated for patients treated with rivaroxaban or apixaban when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding. The initial approval included a Boxed Warning for thromboembolic risks.
The accelerated approval was granted based on changes from baseline in anti-activated FXa activity in healthy volunteers, serving as a surrogate endpoint reasonably likely to predict clinical benefit. As a condition of approval, AstraZeneca was required to conduct the ANNEXA-I trial to verify clinical benefit.
Global Impact and Hong Kong Response
In Hong Kong, Andexxa Powder For Solution For Infusion 200mg is registered by AstraZeneca Hong Kong Limited as a prescription-only medicine. The Hong Kong Department of Health confirmed that the product has been distributed to only two public hospitals and three private hospitals since its registration in February 2024.
Following the FDA announcement, Hong Kong health authorities contacted AstraZeneca, which confirmed it will send notification letters to the affected hospitals. These communications will advise physicians on the safety update and recommend using Andexxa only after careful benefit-risk assessment. The Department of Health has not received any adverse drug reaction reports regarding Andexxa in Hong Kong.
The FDA emphasized its commitment to continuous monitoring and assessment of all biological products' safety, stating it remains dedicated to informing the public when new safety information becomes available. The agency will continue working with AstraZeneca to keep healthcare providers and the public informed as the company prepares to end Andexxa sales.