Astrazeneca Shares Climb 0.64% Amid 24.2% Volume Drop Ranking 239th as FDA Forces Andexxa Exit Over Safety Concerns

Market Snapshot

On December 23, 2025, Astrazeneca (AZN) shares rose 0.64%, closing with a modest gain despite a 24.2% decline in trading volume to $0.32 billion, ranking 239th in market activity. This divergence between volume contraction and price appreciation highlights mixed investor sentiment, with the stock outperforming broader market trends. The volume drop suggests reduced short-term trading interest, while the positive price movement indicates potential optimism about the company’s strategic adjustments or broader sector dynamics.

Key Drivers

The U.S. Food and Drug Administration (FDA)’s decision to flag safety concerns with Astrazeneca’s anticoagulant therapy Andexxa triggered a major strategic shift for the company. The agency concluded that the drug’s risk profile, particularly its association with thromboembolic events—including fatal cases—no longer justified its benefits. This led to Astrazeneca voluntarily withdrawing the drug’s biologics license and exiting the U.S. market by December 22, 2025. The FDA’s review of post-marketing safety data revealed a significant increase in thrombosis incidents among Andexxa-treated patients compared to usual care, culminating in six thrombosis-related deaths within 30 days in the treatment group. These findings forced the company to reassess its commercial strategy, despite Andexxa’s 2018 accelerated approval for reversing bleeding caused by anticoagulants like Eliquis and Xarelto.

The ANNEXA-I Phase III trial, submitted in January 2024, provided critical data that undermined Andexxa’s long-term viability. The trial showed a 14.6% incidence of thrombosis in the Andexxa arm versus 6.9% in the control group, with over half of the thrombotic events occurring earlier in the treatment group. While the drug initially demonstrated efficacy in reversing anticoagulation, the heightened risk of severe complications rendered it commercially unsustainable in the U.S. Astrazeneca’s decision to exit the market reflects the financial and reputational costs of maintaining a product with an unfavorable risk-benefit profile, especially given the $81 million in U.S. sales the drug generated in 2024.

Regulatory scrutiny extended beyond the U.S., with the European Medicines Agency (EMA) and the UK’s Medicines and Healthcare Regulatory Agency (MHRA) maintaining conditional approvals for Andexxa. However, the unfavorable post-marketing data raises questions about the drug’s future in other markets, where regulators may follow the FDA’s lead. Astrazeneca’s acquisition of Andexxa through its $39 billion purchase of Alexion in 2021, and Alexion’s prior $1.4 billion acquisition of Portola Pharmaceuticals, underscores the high stakes involved. The company’s swift exit from the U.S. market signals a strategic pivot to mitigate losses and focus on other high-potential assets, despite the drug’s initial promise in addressing unmet medical needs.

Analyst sentiment remains divided, with recent price targets ranging from a “Sell” at $105 to a “Buy” at $155. The mixed guidance reflects uncertainty about Astrazeneca’s ability to offset Andexxa’s exit with other products. While the stock closed with a 0.64% gain, the broader market reaction to the FDA’s decision appears muted, suggesting investors may be factoring in the company’s strong pipeline and diversified portfolio. The withdrawal of Andexxa, however, serves as a cautionary tale about the long-term risks of relying on accelerated approvals without robust confirmatory data—a challenge facing the entire pharmaceutical sector.

The financial implications of Andexxa’s exit are significant, with global sales dropping from $219 million in 2024. Astrazeneca’s decision to halt U.S. manufacturing and sales by year-end 2025 will require careful resource reallocation, particularly as it navigates regulatory hurdles in other regions. The company’s proactive approach to addressing safety concerns may help preserve its reputation, but the loss of a high-margin product in a competitive anticoagulant market could weigh on short-term earnings. This case highlights the delicate balance pharmaceutical firms must strike between innovation and patient safety in an increasingly risk-averse regulatory environment.