FDA Grants Approval to Andexanet Alfa for Rapid NOAC Reversal

The U.S. Food and Drug Administration (FDA) has granted approval to andexanet alfa (Andexxa) as the first antidote indicated for the patients treated with rivaroxaban (Xarelto) and apixaban (Eliquis), the inhibitors of Factor Xa, announced by Andexxa's manufacturer Portola Pharmaceuticals.

Andexanet alfa is indicated for reversing the anticoagulant effects of the Factor Xa inhibitors. ANNEXA-4 investigators had reported massive reductions in anti-Factor Xa activity among rivaroxaban and apixaban recipients within hours of andexanet administration. This will help clinicians to treat life-threatening bleeds.

The use of Factor Xa inhibitors is rapidly growing because of their efficacy and safety profile compared to enoxaparin and warfarin in preventing and treating thromboembolic conditions such as stroke, pulmonary embolism and venous thromboembolism (VTE). This growth has come with a related increase in the incidence of hospital admissions and deaths related to bleeding, the major complication of anticoagulation. In the U.S. alone in 2016, there were approximately 117,000 hospital admissions attributable to Factor Xa inhibitor-related bleeding and nearly 2,000 bleeding-related deaths per month.

Its approval is supported by data from two Phase 3 ANNEXA studies published in The New England Journal of Medicine, which evaluated the safety and efficacy of Andexxa in reversing the anticoagulant activity of the Factor Xa inhibitors rivaroxaban and apixaban in healthy volunteers. As described in the label, results demonstrated that Andexxa rapidly and significantly reversed anti-Factor Xa activity.

SELECT IMPORTANT SAFETY INFORMATION

• Thromboembolic Risk- Arterial and venous thromboembolic events, ischemic events, sudden deaths, or events where a thrombotic event could not be ruled out were observed within 30 days post- Andexxa administration in 33 of the 185 patients (17.8%) evaluable for safety in the ongoing ANNEXA-4 study.


• Re-elevation or Incomplete Reversal of Anti-FXa Activity- There was a rapid and substantial decrease in anti-FXa activity corresponding to the Andexxa bolus.


• Adverse Reactions- The most common adverse reactions (≥ 5%) in patients receiving Andexxa were urinary tract infections and pneumonia.


• Immunogenicity- As with all therapeutic proteins, there is potential for immunogenicity. Low titers of anti-Andexxa antibodies were observed in 26/145 healthy subjects.

Treatment with Andexxa has been associated with serious and life‑threatening adverse events, including:

• Arterial and venous thromboembolic events


• Ischemic events, including myocardial infarction and ischemic stroke


• Cardiac arrest


• Sudden deaths

Portola plans a limited launch in early June, with a broader commercial launch coming in early 2019 when the FDA is expected to approve an updated manufacturing process. The agency didn't clear the reversal agent in its first try in 2016, asking for additional information related to manufacturing instead.

For further information click on the link: 10.1056/NEJMoa160788