Key Points to Consider When Evaluating Andexxa for Formulary Addition

Abstract

, Andexxa (coagulation factor Xa [recombinant], inactivated-zhzo or formerly andexanet alfa) received accelerated approval from the Food and Drug Administration (FDA) as a specific reversal for rivaroxaban-and apixaban-treated patients with life-threatening or uncontrolled bleeding despite not establishing improvement in hemostasis [1]. The recent publication of ANEXXA-4 and the wider availability for Andexxa in 2019 has led many hospital Pharmacy and Therapeutics (P&T) committees to discuss whether Andexxa should be added to formulary [2]. Currently, there are no studies comparing the safety and efficacy of Andexxa to the current standard of care. The ANNEXA-4 study and clinical trials with prothrombin complex concentrate (PCC) also have their limitations. Furthermore, the off-label use and FDA concerns, conflicting society recommendations, and financial impact add another challenging layer to this evaluation. In this article, we discuss key aspects to consider when evaluating Andexxa for formulary addition.

Evaluation of andexanet alfa and four‐factor prothrombin complex concentrate (4F‐PCC) for reversal of rivaroxaban‐ and apixaban‐associated intracranial hemorrhages

“…8 However, despite a reported 92% reduction in anti-FXa activity at the end of the andexanet alfa bolus administration, clinician concerns regarding its efficacy and superiority were raised given its short duration of action and noted limitations in the open-label single arm clinical trial. 18,[30][31][32] In 171 patients with ICH evaluated in the efficacy population, excellent or good hemostatic efficacy was achieved in 80% of patients and 30-day thrombosis event rate was 10%. 32 Furthermore, the high drug acquisition costs for andexanet alfa brought forth concerns on the sustainability of widespread use of an andexanet alfa after United States Food and Drug Administration (FDA) approval without clear superiority in achievement of good outcomes or safety.…”

“…Comparatively, andexanet alfa is a recombinant human FXa decoy protein that binds directly to rivaroxaban and apixaban to reverse their anticoagulant effect 8 . However, despite a reported 92% reduction in anti‐FXa activity at the end of the andexanet alfa bolus administration, clinician concerns regarding its efficacy and superiority were raised given its short duration of action and noted limitations in the open‐label single arm clinical trial 18,30‐32 . In 171 patients with ICH evaluated in the efficacy population, excellent or good hemostatic efficacy was achieved in 80% of patients and 30‐day thrombosis event rate was 10% 32 .…”

Treatments in Ischemic Stroke: Current and Future

“…The ANNEXA-4 sub-study results, evaluating the hemostatic efficacy of andexanet alfa in ICH secondary to anti-FXa, reported a reduced anti-FXa activity in FXa inhibitor-treated patients with ICH, with a high rate of hemostatic efficacy [102]. Andexanet alfa has been recently approved by the US Food and Drug Administration, but some issues slow down its widespread use, such as its brief half-life, poor correlation between in vitro activity and clinical efficacy, and finally, regarding its safety profile, given the in vitro effects and clinical thrombosis rates of up to 18% in early studies [103]. Other promising reversal agents, with an extended indication on anticoagulants, are aripazine and ciraparantag.…”

Ciraparantag reverses the anticoagulant activity of apixaban and rivaroxaban in healthy elderly subjects

“… 6 A second agent recently approved, andexanet alfa (Andexxa ® , Alexion Pharmaceuticals, Inc.), is a modified, enzymatically inactive recombinant FXa functioning as a decoy Xa targeted to bind to and reverse the oral FXa inhibitors as well as enoxaparin, 7 but it has some challenges to its widespread use. 8 Hence, there remains an unmet need for agents that can rapidly reverse the effects of DOACs in emergency settings.…”