General Information

Jivi (antihemophilic factor [recombinant] PEGylated-aucl) works by replacing the reduced or missing factor VIII (FVIII) in patients with hemophilia A.

Jivi is specifically indicated for use in previously treated adults and adolescents (12 years of age and older) with hemophilia A (congenital Factor VIII deficiency) for: • On-demand treatment and control of bleeding episodes • Perioperative management of bleeding • Routine prophylaxis to reduce the frequency of bleeding episodes.

Jivi is supplied as a solution for intravenous administration. The recommended dose is as follows:

Control of bleeding episodes and perioperative management: •Expected recovery: one unit per kilogram body weight of Jivi will increase the Factor VIII level by 2 international units per deciliter (IU/dL). Each vial of Jivi contains the labeled amount of recombinant Factor VIII in IU (3). • Required dose (IU) = body weight (kg) x desired Factor VIII rise (% of normal or IU/dL) x reciprocal of expected recovery (or observed recovery, if available). • Estimated Increment of Factor VIII (IU/dL or % of normal) = [Total Dose (IU)/body weight (kg)] x 2 (IU/dL per IU/kg).

Routine prophylaxis: The recommended initial regimen is 30–40 IU/kg twice weekly. • Based on the bleeding episodes: • The regimen may be adjusted to 45–60 IU/kg every 5 days. • A regimen may be further individually adjusted to less or more frequent dosing.

Clinical Results

FDA Approval

The FDA approval of Jivi was based on the PROTECT VIII study, a 36-week, Phase II/III, international, open-label trial conducted in previously treated adults and adolescents 12 years of age or older with severe hemophilia A. Part A evaluated pharmacokinetics, efficacy and safety of Jivi for on-demand treatment of bleeds and for prophylactic therapy at different dosing regimens. art B evaluated safety and efficacy of Jivi during major surgery. The study achieved its primary objective of protection from bleeding with fewer infusions. The site-specific PEGylated factor VIII demonstrated increased protection against bleeding when used prophylactically every seven days, every five days, and twice per week. Efficacy was also achieved in the treatment of acute and breakthrough bleeding, with 91% of bleed events resolved with only one or two infusions.

Mechanism of Action

Jivi is a site-specifically PEGylated recombinant antihemophilic factor which temporarily replaces the missing coagulation Factor VIII. The site-specific PEGylation in the A3 domain reduces binding to the physiological Factor VIII clearance receptors resulting in an extended half-life and increased AUC .