Regulatory Decision Summary for Ondexxya
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
All other therapeutic products
Type of Submission:
New Drug Submission (New Active Substance)
Authorized; issued a Notice of Compliance in accordance with the Food and Drug Regulations, as per the Notice of Compliance with Conditions Guidance
What was the purpose of this submission?
The purpose of this New Drug Submission (NDS) was to seek a Notice of Compliance with Conditions (NOC/c) for Ondexxya for the treatment of adult patients treated with factor Xa (FXa) inhibitors (rivaroxaban or apixaban) when rapid reversal of anticoagulation is needed due to acute major bleeding, including life-threatening bleeds.
The authorized indication is:
Ondexxya (andexanet alfa) is indicated for:
adult patients treated with FXa inhibitors (rivaroxaban or apixaban) when rapid reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.
Ondexxya has not been shown to be effective for, and is not indicated for, the treatment of bleeding related to any FXa inhibitors other than apixaban or rivaroxaban.
Why was the decision issued?
Rivaroxaban and apixaban are direct oral anticoagulants (DOACs), marketed in Canada, for which there are no specific reversal agents available. Andexanet alfa, brand name Ondexxya, contains recombinant factor X modified to ensure that it has no pro-coagulant activity but binds with high affinity to rivaroxaban or apixaban, which effectively inhibits their pharmacological activity. Life-threatening bleeding among anticoagulated patients is a serious condition associated with a high rate of mortality. Quickly achieving hemostasis is expected to reduce overall mortality, and the availability of a rapid-acting DOAC reversal agent could facilitate this goal.
The benefit of Ondexxya is primarily based on pharmacodynamic data from healthy volunteer studies in which subjects received either rivaroxaban or apixaban until steady state, which was followed by Ondexxya dosing. The studies demonstrated that Ondexxya rapidly reduces anti-FXa activity to low levels while also reducing the free fraction of DOAC in circulation and increasing thrombin generation, which are reasonably likely to impact on the goal of achieving hemostasis.
A single-arm study of Ondexxya in bleeding patients evaluated anti-FXa activity and the outcome of hemostatic efficacy. Among patients who received DOACs, hemostatic efficacy ratings of good or excellent were achieved by the majority of patients (80%) while the anti-FXa activity time profile was similar to that observed in healthy volunteer studies.
The risks associated with Ondexxya treatment, as observed in randomized studies in healthy volunteers, were limited to infusion-related reactions. In bleeding patients, Ondexxya treatment in combination with the discontinuation of DOACs results in exposure to underlying risk factors for serious thromboembolic and ischemic events. These risks are mitigated via warnings and precautions included in the product monograph, which includes advisement to restart DOAC therapy as early as possible.
Overall, the benefits observed in healthy volunteers and patients are considered to outweigh the risks of Ondexxya treatment when used in the treatment of patients with life-threatening or uncontrolled bleeding, who require reversal of rivaroxaban or apixaban anticoagulation, according to the directions in the product monograph.
Ondexxya is administered by intravenous bolus followed by intravenous infusion. The recommended dose depends on the DOAC received prior to treatment, the dose of the DOAC and the timing since the last dose of DOAC. Based on these factors, patients could receive either 400 mg as an IV bolus followed by 480 mg as an IV infusion or 800 mg as an IV bolus followed by 960 mg as an IV infusion. See the product monograph for Dosage and Administration guidance.
Health Canada granted this application advanced consideration under the NOC/c policy.
For further details about Ondexxya, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.
Date of Decision:
Manufacturer / Sponsor:
Drug Identification Number(s) Issued:
Available by prescription only