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XARELTO®

(rivaroxaban)

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XARELTO® (rivaroxaban)

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SPECIFIC RESPONSE

XARELTO - Reversal Agents in Human Studies - Andexanet alfaa (PRT064445) - ANNEXA-R

Last updated : 05/16/2024

ANNEXA-R1 was a phase 3, randomized, double‑blind, placebo-controlled study in older healthy subjects to evaluate the safety and efficacy of andexanet to reverse the anticoagulant effects of XARELTO.

Study Design1

Baseline Characteristics1

  • The treatment groups were balanced with respect to baseline characteristics.

Baseline Characteristics1

Part 1

  • A bolus of andexanet rapidly (within 2-5 minutes) reduced anti–factor Xa activity to a greater extent than placebo in subjects receiving XARELTO.1
  • Reversal of anti–factor Xa activity persisted for 2 hours after completion of the andexanet bolus.1

Part 2

  • When administered as a bolus plus a 2-hour infusion, andexanet reduced anti–factor Xa activity to a greater extent than placebo.1
    • In the placebo group, anti–factor Xa activity decreased over time at the expected rate for clearance of the anticoagulant.
  • Reversal of anti–factor Xa activity with andexanet persisted for 1-2 hours after completion of the infusion.1
  • All andexanet-treated subjects had at least 80% reversal of anti–factor Xa activity, with the exception of 1 subject who did not receive the full dose of andexanet due to a malfunction with the IV administration, compared with none of the placebo-treated subjects (P<0.001).1

Safety Results

Adverse events: There were no serious or severe adverse events, and no thrombotic events were reported.1

  • The most common side effects were urticaria and administration site conditions.
  • No subjects developed antibodies to factor X or Xa (measured through day 43).

The publication does not present data on the efficacy and safety of andexanet in patients requiring urgent reversal of factor Xa inhibitor activity for bleeding or emergency surgery. For additional information on this study, please consult the full publication (http://www.nejm.org/doi/pdf/10.1056/NEJMoa1510991).

aAndexxa® (coagulation factor Xa [recombinant], inactivated-zhzo) is a product of AstraZeneca. Please refer to the Andexxa Prescribing Information for complete product information or call AstraZeneca at 1-800-236-9933.
bAnti–factor Xa activity was measured using a validated chromogenic assay of factor Xa enzymatic activity, from baseline (before andexanet/placebo) to nadir (after andexanet/placebo). Nadir was defined as the smaller value for anti–factor Xa activity at 2 and 5 minutes following the end of the bolus for part 1, and the smallest value between 10 minutes before and 5 minutes after the end of the continuous infusion for part 2.

Cmax, maximum plasma concentration; IV, intravenous.

Reference

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1. Siegal DM, Curnutte JT, Connolly SJ, et al. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med. 2015;373(25):2413-2424.