itors) to Factor VIII has occurred following administration of ESPEROCT.
Monitor patients for the development of Factor VIII inhibitors by appropriate clinical observations and laboratory tests. Ifexpected Factor VIII activity plasma levels are not attained, or if bleeding is not controlled after ESPEROCT administration,suspect the presence of an inhibitor (neutralizing antibody) [see Warnings and Precautions (5.3)].
5.3 Monitoring Laboratory Tests
If monitoring of Factor VIII is performed, use a chromogenic or one-stage clotting assay appropriate for use withESPEROCT [see Dosage and Administration (2)].
Factor VIII activity levels can be affected by the type of activated partial thromboplastin time (aPTT) reagent used in theassay. Some silica-based aPTT reagents can underestimate the activity of ESPEROCT by up to 60%; other reagents mayoverestimate the activity by 20%. If an appropriate one-stage clotting or chromogenic assay is not available locally, then usea reference laboratory.
If bleeding is not controlled with the recommended dose of ESPEROCT or if the expected Factor VIII activity levels inplasma are not attained, then perform a Bethesda assay to determine if Factor VIII inhibitors are present.
6 ADVERSE REACTIONS
The most frequently reported adverse reactions (incidence ≥1%) in clinical trials were rash, redness, itching (pruritus), andinjection site reactions.
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials ofa drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in clinicalpractice.
The safety of ESPEROCT has been eva luated in 270 subjects (202 adolescents/adults and 68 children) in five prospective,multi-center clinical studies in previously treated patients (PTPs) with severe hemophilia A (<1% endogenous Factor VIIIactivity) and no history of inhibitors. All subjects received at least one dose of ESPEROCT. A previously treated patient wasdefined as a subject with a history of at least 150 exposure days to other Factor VIII products (adolescent/adult subjects) or50 exposure days to other Factor VIII products (pediatric subjects). Total exposure to ESPEROCT was 80,425 exposure dayscorresponding to 889 patient years of treatment.
During the clinical trials in PTPs, adverse reactions occurred at a rate of 0.10 events per patient year of exposure. The mostfrequently reported adverse reactions were rash (5.2%), injection site reaction (2.6%), redness (1.9%), and itching (pruritus)(1.5%).
6.2 Immunogenicity
Subjects were monitored for neutralizing and non-neutralizing antibodies to Factor VIII, polyethylene glycol (PEG), andCHO host cell protein. One previously treated subject developed confirmed neutralizing antibodies to Factor VIII (13.5Bethesda Units). In addition, two subjects had transient low titer FVIII antibody (<5 Bethesda Units) test results at a singleoccasion. Anti-PEG antibodies of no clinical consequence were detected in 45 subjects, 32 of whom had pre-existing antiPEG
antibodies. Nine subjects developed anti-CHO host cell protein antibodies of no clinical consequence.
The detection of antibodies is highly dependent on the sensitivity and specificity of the assay. Additionally, the observedincidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by severa |
