the completed studies, no PTP developed neutralizing antibodies to Factor VIII. In an ongoing extension study, a 13 year old PTP had a titer of 0.6 BU after 550 EDs concurrent with an acute infection and positive IgG anticardiolipin antibodies. The Factor VIII recovery was 2.2 IU/dL per IU/kg, annualized bleeding rate (ABR) was zero, and no change in therapy was required.
In an actively enrolling clinical trial in PUPs, 6 of 14 treated subjects (42.9% with a 95% Confidence Interval of 17.7-71.1%) developed an inhibitor. Of these, 3 subjects (21.4%) had high titer inhibitors, and 3 subjects (21.4%) had transient low titer inhibitors for which no change in therapy was required.
The detection of antibody formation is 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. For these reasons, it may be misleading to compare the incidence of antibodies to KOVALTRY with the incidence of antibodies to other products.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
There are no data with KOVALTRY use in pregnant women to inform on drug-associated risk. Animal reproduction studies have not been conducted using KOVALTRY. It is not known whether KOVALTRY can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. KOVALTRY should be given to a pregnant woman only if clearly needed. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
8.2 Lactation
Risk Summary
There is no information regarding the presence of KOVALTRY in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for KOVALTRY and any potential adverse effects on the breastfed infant from KOVALTRY or from the underlying maternal condition.
8.4 Pediatric Use
Safety and efficacy studies with KOVALTRY have been performed in pediatric PTPs. Body weight adjusted clearance of Factor VIII in children ≤12 years of age is higher than in adults and adolescents. Consider higher or more frequent dosing in children to account for this difference in clearance [see Clinical Pharmacology (12.3)].
8.5 Geriatric Use
Clinical studies with KOVALTRY did not include patients aged 65 and over to determine whether or not they respond differently from younger patients. However, clinical experience with other Factor VIII products has not identified differences between the elderly and younger patients. As with any patient receiving recombinant Factor VIII, dose selection for an elderly patient should be individualized.
11 DESCRIPTION
KOVALTRY, Antihemophilic Factor (Recombinant), is a sterile, non-pyrogenic, white to slightly yellow powder for reconstitution contained in a single-use vial. The final product does not contain any preservative. The reconstituted product is indicated for intravenous administration. The product is available in 250 IU, 500 IU, 1000 IU, 2000 IU, or 3000 IU nominal potencies; however, for each dosage strength the actual, assayed Factor VIII potency is directly printed on each vial label. The cont |
