Indications and Limitation of Use: ADYNOVATE is indicated for use in adult and pediatric patients with hemophilia A (congenital factor VIII deficiency) for on-demand treatment and control of bleeding episodes, perioperative management, and routine prophylaxis to reduce the frequency 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 478 previously treated patients (PTPs) and previously untreated patients (PUPs) with severe hemophilia A, who received at least one dose of ADYNOVATE in 7 completed clinical trials.1
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
In PTPs, immunogenicity was evaluated in 6 clinical trials (N=365).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
In PUPs, immunogenicity was evaluated in 1 clinical trial (N=120); 100 patients were evaluable for inhibitor development.1
- Eleven (11%) patients developed confirmed FVIII inhibitors to ADYNOVATE, 6 (55%) high-titer and 5 (45%) low-titer;* 89 patients (89%) did not develop FVIII inhibitors1
- Of the 120 patients, pre-existing binding antibodies were identified in 4 (3%) IgG to FVIII, 13 (11%) IgM to PEG, 11 (9%) IgG to PEG FVIII, 7 (6%) IgM to PEG FVIII, and 59 (49%) developed transient binding non-neutralizing antibodies to FVIII, PEG FVIII, and PEG after exposure to ADYNOVATE that had no clinical impact1
*Inhibitor development: high-titer (>5 BU/mL) and low-titer (≤5 BU/mL).
PEG=polyethylene glycol
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 6 clinical trials has shown1
zero Inhibitors Seen in Previously Treated Patients (N=237) in Clinical Studies1,2†- 1 PTP developed a transient low-titer FVIII inhibitor while receiving more frequent dosing of ADYNOVATE1‡
- 1 PTP from an ongoing study developed a transient low-titer FVIII inhibitor1‡
Data from 1 clinical trial in PUPs has shown
eleven Inhibitors Developed in Previously Untreated Patients (N=120; 100 Patients Were Evaluable for Inhibitor Development)1†- 6 (55%) were high titer¶
- 5 (45%) were low titer¶
†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
¶Inhibitor development: high-titer (>5 BU/mL) and low-titer (≤5 BU/mL)1
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
