The most frequently reported adverse reactions ( ≥ 0.5%) were injection site reactions, increased hepatic enzymes, and pyrexia.
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in clinical practice.
During the clinical development of Novoeight, 214 male previously treated patients (PTPs; exposed to a factor VIII-containing product for ≥ 150 days) with severe hemophilia A (factor VIII level ≤ 1%) received at least one dose of Novoeight as part of either routine prophylaxis, on-demand treatment of bleeding episodes, perioperative management of major and minor surgical, dental, or other invasive procedures, or pharmacokinetic evaluation of Novoeight. Thirty-one subjects (14%) were < 6 years of age, 32 (15%) were 6 to < 12 years of age, 16 (7%) were adolescents (12 to < 16 years of age), and 135 (63%) were adults (16 years of age and older). The subjects received a total of 33,272 injections with a median of 127 injections of Novoeight (range 1-442) per subject, and had a total of 32,929 exposure days during prevention and treatment of bleeds.
The most frequently reported adverse reactions in previously treated patients was injection site reactions (2.3%), increased hepatic enzymes (1.4%), and pyrexia (0.9%).
Subjects were monitored for neutralizing antibodies to factor VIII and binding antibodies to CHO and murine protein. No subjects developed confirmed neutralizing antibodies to factor VIII. One twenty-two month old child had a positive neutralizing antibody to factor VIII of 1.3 [BU] in the Bethesda assay after 15 exposure days that was not confirmed when checked after 20 exposure days. In vivo recovery was normal for this child and no clinical adverse findings were observed.
No patients developed de novo anti-murine antibodies. Nineteen subjects were positive for anti-Chinese hamster ovary (CHO) cell protein antibodies. Two of these subjects changed from anti-CHO negative to anti-CHO positive and 6 subjects changed from anti-CHO positive to anti-CHO negative. The remaining 11 subjects were either positive throughout the trials (n=6), negative at baseline and end-of trial but with transient positive samples (n=2), or positive at baseline and end-of trial but with negative samples in between (n=3). No clinical adverse findings were observed in any of these subjects.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.