IQWiG Reports Negative Effects of Andexanet alfa in Treating Intracerebral Hemorrhages

Intracerebral hemorrhages pose a significant risk for patients on anticoagulant therapy, making timely intervention crucial to halt bleeding. The Institute for Quality and Efficiency in Health Care (IQWiG) recently assessed the therapeutic benefits of Andexanet alfa, an antidote introduced to counteract the effects of direct oral anticoagulants (DOACs) like apixaban and rivaroxaban.

Initially, DOACs were praised for their ease of use and lower risk of interactions compared to traditional vitamin K antagonists (VKAs) such as phenprocoumon. However, their adoption faced challenges, particularly due to the absence of a specific antidote, raising concerns among healthcare providers about managing potential bleeding emergencies.

In 2019, the approval of Andexanet alfa in Europe alleviated some of these concerns as it specifically targets the effects of factor Xa inhibitors. This modified human factor Xa molecule works by binding to these anticoagulants, rendering them ineffective and potentially mitigating life-threatening bleeding scenarios.

Despite the theoretical advantages of Andexanet alfa, IQWiG's latest evaluation indicates a lack of confirmed benefits in real-world clinical scenarios. Their findings suggest that the added therapeutic value of Andexanet alfa in cases of severe or uncontrolled bleeding is unsubstantiated.

IQWiG based its assessment on a comparative study submitted by the manufacturer, which primarily involved patients experiencing intracerebral bleeding while on apixaban or rivaroxaban. Participants were treated with either Andexanet alfa or an individualized therapy using alternative medications.

However, IQWiG criticized the primary endpoint of the study, which focused on effective hemostasis, deeming it not sufficiently relevant for practical benefit assessments. The criteria stipulated that hematomas must not expand by more than 35% within 12 hours post-randomization, raising questions about the clinical significance of this measure.

In contrast, the adverse effects associated with Andexanet alfa, including cardiovascular complications, thrombotic events, and ischemic strokes, raise significant concerns about its safety profile. According to Dr. Daniela Preukschat, head of the Drug Assessment department at IQWiG, the relevance of these side effects to patient well-being is undeniable.

Consequently, IQWiG has concluded that the overall benefit-risk ratio for Andexanet alfa in cases of intracerebral hemorrhage is negative, and it indicates a potentially lower therapeutic benefit compared to existing treatments. For bleeding incidents outside the brain, there remains no evidence of added benefit.

The IQWiG's evaluation will be forwarded to the Joint Federal Committee (G-BA), which will make the final determination regarding the additional therapeutic value of Andexanet alfa.