The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for damoctocog alfa pegol, a recombinant human factor VIII therapy.
Bayer is seeking European marketing authorization for damoctocog alfa pegol (formerly BAY94-9027) for the treatment and prophylaxis of bleeding in previously treated patients age 12 and older with hemophilia A.
The CHMP’s recommendation for damoctocog alfa pegol, which is approved in the U.S. under the name Jivi, will be reviewed by the European Commission (EC).
The EC typically makes a decision about marketing authorization within 67 days of the CHMP’s opinion. The EC’s decision will apply to the European Union, Norway, Iceland, and Liechtenstein.
The CHMP’s recommendation for damoctocog alfa pegol is supported by the phase 2/3 PROTECT VIII trial. Some results from this trial were published in the Journal of Thrombosis and Haemostasis in 2016. Additional results are available in the U.S. prescribing information for Jivi.
PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.
In part A, researchers evaluated different dosing regimens for damoctocog alfa pegol used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A.
In part B, researchers evaluated damoctocog alfa pegol 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 damoctocog alfa pegol 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) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).
The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).
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. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were considered “moderate,” and 3.3% were considered “poor.”
There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A. Damoctocog alfa pegol provided “good” or “excellent” hemostatic control during all surgeries.
Safety data are available for 148 patients age 12 and older.
Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).
A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.
One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.