FDA approves new factor VIII product for hemophilia A


The Food and Drug Administration (FDA) has approved Jivi (antihemophilic factor [recombinant] PEGylated-aucl) for the treatment of hemophilia A.

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Jivi (formerly BAY94-9027), a DNA-derived, factor VIII concentrate, is now approved for use in previously treated adults and adolescents – aged 12 years and older – with hemophilia A.

The product is also approved for on-demand treatment and control of bleeding episodes, for perioperative management of bleeding, and as routine prophylaxis to reduce the frequency of bleeding episodes.

The initial recommended prophylactic regimen is dosing twice weekly (30-40 IU/kg) with the ability to dose every 5 days (45-60 IU/kg) and to further individually adjust to less or more frequent dosing based on bleeding episodes.

The FDA’s approval of Jivi is based on results from the phase 2/3 PROTECT VIII trial. Some results from this trial were published in the Journal of Thrombosis and Haemostasis (2017 Mar;15[3]:411-419). Additional results are available in the prescribing information for Jivi. The product is marketed by Bayer.

PROTECT VIII enrolled previously treated adults and adolescents with severe hemophilia A. In part A, researchers evaluated different dosing regimens for Jivi used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A. In part B, researchers evaluated Jivi for perioperative management.

In part A, there were 132 patients in the intent‐to‐treat population – 112 in the prophylaxis group and 20 in the on-demand group.

Patients received Jivi for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.

Patients with more than one bleed during this time went on to receive 30-40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45-60 IU/kg) or every 7 days (60 IU/kg).

The median annualized bleeding rate (ABR) for the patients who were treated twice weekly and were not eligible for randomization (n = 13) improved after their dose increase. Their median ABR decreased from 17.4 to 4.1.

The median ABR for patients who were randomized to treatment every 5 days (n = 43) was 1.9. The median ABR was also 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n = 11). The median ABR for patients who completed prophylaxis with dosing every 7 days (32/43) was 0.96. The median ABR for patients treated on demand was 24.1.

There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group.

The safety data in the prescribing information includes 221 patients from three studies. The 17 patients who received Jivi for perioperative management were excluded from the pooled safety analysis but included in the analysis for inhibitor development.

In the 148 patients aged 12 years and older who were exposed to Jivi, adverse events included abdominal pain, nausea, vomiting, injection site reactions, pyrexia, hypersensitivity, dizziness, headache, insomnia, cough, erythema, pruritus, rash, and flushing.

A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.

One adult patient with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.

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