AHA 2021: Bentracimab rapid and safe to reverse Ticagrelor's effects, REVERSE IT study.

Bentracimab, an intravenous reversal agent for ticagrelor, has shown immediate and sustained reversal of the Tiacgrelor's antiplatelet effects in both patients undergoing surgery and those with major bleeding, according to a prespecified interim analysis of the REVERSE-IT study presented this week at AHA, 2021.

The drug is a recombinant IgG1 monoclonal antibody fragment that binds to both ticagrelor and its major active circulating metabolite, reversing the antiplatelet effects within 5 minutes. Previous phase I data in healthy participants, published in 2019, sparked excitement as a potential answer to the challenges faced not just by surgeons, but also by physicians when patients on ticagrelor present with an intracranial hemorrhage, for example, and can't wait the recommended 5 days for the drug's effects to wear off.

The goal of the REVERSE IT trial was to assess the safety and efficacy of bentracimab in reversing the antiplatelet effect of ticagrelor among patients needing urgent surgery or a procedure, or with major bleeding.

The inclusion criteria were as follows:

• Last ticagrelor dose within 3 days

• Age ≥18 years

• Patients needing urgent surgery or a procedure (when it is not medically advisable either to proceed urgently with impaired hemostasis or to delay the urgent procedure for 3 or more days as directed by ticagrelor labeling due to the high risk of bleeding) or with major bleeding

On day 1, patients received an intravenous (IV) infusion of an initial IV bolus of 6 g infused over 10 minutes for rapid reversal, followed immediately by a 6 g IV loading infusion over 4 hours and then a 6 g IV maintenance infusion over 12 hours (total 18 g). A higher dose of 36 g could be used in patients with potential drug interaction from recent concomitant use of moderate or strong CYP3A inhibitors with ticagrelor.

The primary reversal endpoint, minimum % inhibition of VerifyNow PRU(Platelet reactivity units) within 4 hours of bentracimab initiation, was successfully met.

PRUs increased from a baseline of <100 to greater than 200 within 5-10 minutes with a steady increase by 4 hours, and appeared to be sustained for 24 hours. Platelet inhibition results were consistent for patients needing urgent surgery/procedure or with major bleeding.

There was no evidence of platelet rebound activity, as measured by P-selectin and mean platelet volumes. The results of this phase III trial indicate that bentracimab is safe and effective in reversing the antiplatelet effect of ticagrelor. Reversal was noted within 5 minutes, and the duration of reversal was infusion-time dependent. Effective hemostasis was achieved in most cases and no rebound increase in platelet activity was noted.

Source: AHA 2021: https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2021/11/12/21/17/REVERSE-IT