Higher FVIII Blood Levels Seen and Better Maintained with Jivi Than Eloctate, Phase 1 Study in Severe Hemophilia A Finds

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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AMT-061, Phase 3 trial data

Bayer’s Jivi, an FVIII replacement therapy for hemophilia A, has a longer half-life and a slower clearance from blood circulation than Eloctate, and may protect against bleeding for longer periods, results of a Phase 1 trial in people with severe disease suggests.

The study “Direct comparison of two extended-half-life recombinant FVIII products: a randomized, crossover pharmacokinetic study in patients with severe hemophilia A” was published in the journal Annals of Hematology.

Preventive (prophylactic) treatment with FVIII is used by both adults and children with severe hemophilia A. Treatment benefits include less bleeding and better joint function. However, FVIII replacement medicines have low stability, meaning the therapy must be taken often to be effective, with the likelihood of three or more infusions every week.

Jivi (BAY94-9027), a lab-made version of the blood clotting factor VIII (FVIII), was designed to overcome this limitation through the addition of PEG, or PEGylation, a substance that, once bound to FVIII, improves its stability and significantly prolongs its half-life in the blood. Half-life refers to the time the body takes to metabolize and eliminate half the amount of a compound.

The PEG molecule is not toxic and also helps to lessen an immune response against therapeutic FVIII. In this way, Jivi is able to stay for longer periods in blood circulation, reducing the number of necessary treatments.

Jivi is approved in the U.S., in Canada, Europe and in Japan for the prophylactic and on-demand treatment of adults and adolescents (age 12 and older) with hemophilia A, although in some countries patients may need to have tried other therapies.

Bioverativ’s (a Sanofi company) Eloctate — marketed as Elocta in Europe and the Middle East — is also a lab-made clotting factor with an extended half-life and approved for people with hemophilia A. In clinical studies, Eloctate was shown to have a longer half-life than conventionally engineered FVIII therapies.

In the open-label and cross-over, recently concluded Phase 1 trial (NCT03364998), researchers compared how a patient’s body processes (a measure called pharmacokinetics) Jivi head-to-head with Eloctate.

The trial randomized 18 adults, mean age of 36, with severe hemophilia A (levels of FVIII < 1 IU/dL) who had previously been treated with an FVIII (for more than 150 days) to single doses of Jivi or Eloctate (both administered at 60 IU/kg). After a seven-day wash-out period following either treatment, patients then switched groups — meaning they move to a single dose of the other therapy.

Results showed that after a single infusion, FVIII blood levels stayed above 1 IU/dL for 13 hours longer in those given Jivi compared to those given Eloctate. The concentration of FVIII in the blood was also 25% higher in the Jivi group, and clearance from circulation was 20% lower with Jivi compared to Eloctate.

FVIII staying in circulation with Jivi suggests this therapy can protect for longer periods against bleeding, requiring less frequent dosing.

“Real-world data” the researchers concluded, “may provide an insight into whether these PK [pharmacokinetic] advantages provide additional bleeding protection.”