Indications and Limitation of Use: ADYNOVATE® [Antihemophilic factor (Recombinant), PEGylated] is a human antihemophilic factor indicated for use in children and adults with hemophilia A for the control and prevention of bleeding episodes. ADYNOVATE is not indicated for the treatment of von Willebrand disease.1
An established and consistent safety profile across clinical studies1
study design
Pooled safety data evaluation
The safety of ADYNOVATE was evaluated in patients (children and adults) (N=365) with severe hemophilia A who received at least 1 dose of ADYNOVATE in 6 completed multicenter, prospective, open-label clinical studies and 1 ongoing clinical study.
Additional immunogenicity evaluations
Immunogenicity also evaluated the development of binding IgG and IgM antibodies against factor VIII, PEGylated
(PEG)-factor VIII, and PEG and Chinese hamster ovary (CHO) protein.1
- Persistent treatment-emergent binding antibodies against FVIII, PEG-FVIII, or PEG were not detected.
- Out of 365 patients, 36 patients in total showed pre-existing antibodies to factor VIII (n=5), PEG-factor VIII (n=31), and/or PEG (n=6) prior to the first exposure to ADYNOVATE
- 24 patients who tested negative at screening developed transient antibodies against factor VIII (n=10) or PEG-FVIII (n=16) and/or PEG (n=3) at 1 or 2 consecutive study visits1
- Antibodies were transient and not detectable at subsequent visits1
SELECTED IMPORTANT RISK INFORMATION
WARNINGS & PRECAUTIONS
Neutralizing Antibodies: Formation of neutralizing antibodies (inhibitors) to factor VIII can occur following administration of ADYNOVATE. Monitor patients regularly for the development of factor VIII inhibitors by appropriate clinical observations and laboratory tests. Perform an assay that measures factor VIII inhibitor concentration if the plasma factor VIII level fails to increase as expected, or if bleeding is not controlled with expected dose.
See Detailed Important Risk Information below.
study results
Data from 7 clinical trials has shown1
zero Inhibitors Seen in Previously Treated Patients at Completion of 6 Clinical Studies†1,2- 1 PTP developed a transient low-titer FVIII inhibitor at 0.6 BU while receiving more frequent dosing on ADYNOVATE in a randomized controlled trial comparing different dosing regimens‡
- 1 PTP from an extension study developed a transient low titer (0.6 BU) FVIII inhibitor‡
- Persistent treatment emergent binding antibodies against FVIII and PEG-FVIII were not detected‡
†Inhibitors defined as ≥0.6 BU using the Nijmegen modification of the Bethesda assay
‡Repeat testing did not confirm the presence of inhibitor. Both of these patients continued treatment without change in the dose of ADYNOVATE
EDs=exposure days; IgG=immunoglobulin G; IgM=immunoglobulin M;
BU=Bethesda Unit; PTP=previously treated patient
SELECTED IMPORTANT RISK INFORMATION
WARNINGS & PRECAUTIONS
Neutralizing Antibodies: Formation of neutralizing antibodies (inhibitors) to factor VIII can occur following administration of ADYNOVATE. Monitor patients regularly for the development of factor VIII inhibitors by appropriate clinical observations and laboratory tests. Perform an assay that measures factor VIII inhibitor concentration if the plasma factor VIII level fails to increase as expected, or if bleeding is not controlled with expected dose.
See Detailed Important Risk Information below.
IMPORTANT RISK INFORMATION
