SELECTED IMPORTANT SAFETY INFORMATION: KOVALTRY®
is contraindicated in patients who have a history of hypersensitivity reactions to the active substance, to any of the excipients, or to mouse or hamster proteins.
KOVALTRY Efficacy & Safety: Children
Study design for LEOPOLD Kids
| LEOPOLD Kids Trial—Part A1 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Study description | Multinational, open-label, prospective trial evaluating the pharmacokinetics, efficacy, safety, and perioperative management of bleeding with KOVALTRY® Previously treated male patients (PTPs) aged 0–<6 years (n=25) and aged 6–12 years (n=26) with severe hemophilia A (<1% FVIII) (n=51) studied for 6 months | |||||||||
| Dosing | Dosing regimens were determined by the investigators to meet individual patients' needs 2x/week prophylaxis: 25–50 IU/kg 3x/week or every-other-day (EOD) prophylaxis: 25–50 IU/kg
| |||||||||
| Primary efficacy endpoint | Annualized number of total bleeds measured during routine prophylaxis, within 48 hours of previous prophylaxis treatment | |||||||||
The Long-Term Efficacy Open-Label Program in Severe Hemophilia A Disease (LEOPOLD) is a 3-part clinical trial program designed to evaluate the pharmacokinetics, efficacy, and safety of KOVALTRY® in patients with severe hemophilia A.
Pharmacokinetic activity in children
Half-life measured via chromogenic assay1
Pharmacokinetic activity was tested after a single 50 IU/kg dose of KOVALTRY® in previously treated children.
| Half-life (arithmetic mean ± SD) | |||
|---|---|---|---|
| 0 to <2 years (n=4) | 2 to <6 years (n=5) | 6 to <12 years (n=10) | |
| Chromogenic assay | 9.6 ± 3.1 hours | 12.2 ± 3.1 hours | 12.0 ± 2.1 hours |
Proven efficacy and safety in previously treated children with KOVALTRY®1
ABR for total bleeds
†During the LEOPOLD Kids study, 1 patient was moved from a 2x/week prophylaxis regimen to a 3x/week prophylaxis regimen.2
People with hemophilia A may develop inhibitors to rFVIII. People with a history of inhibitors and previously untreated children were excluded from LEOPOLD Kids—Part A1
ƚOne case of transient low titer inhibitor (0.6 BU/mL (peak titer: 1.0 BU/mL)) occurred in a 13 year old PTP after 549 EDs concurrent with an acute infection and positive IgG anticardiolipin antibodies. The Factor VIII recovery was normal (2.7 IU/dL per IU/kg), annualized bleeding rate (ABR) was zero, and no change in therapy was required.1
BU=Bethesda units.
EDs=exposure days.
IgG=immunoglobulin G.
PTP=previously treated patient.
On-demand bleed treatment in previously treated children with KOVALTRY®1
During the 6-month study period
of bleeding episodes were resolved with ≤2 infusions of KOVALTRY®.1
Treatment with KOVALTRY® during surgery in children
One previously treated child aged under 12 years with severe hemophilia A underwent major surgery and received KOVALTRY® as bolus infusions1
For the one major surgery in LEOPOLD Kids—Part A, KOVALTRY® dose was 1000 IU before surgery and 1500 IU after surgery, for a total dose of 2500 IU (108.7 IU/kg) on the day of surgery3
Treatment with KOVALTRY® was assessed as good or excellent in all documented surgeries in the LEOPOLD Trials1
Recommended dosing in children1
| KOVALTRY® dosing for routine prophylaxis | Recommended prophylaxis dose | Regimen |
|---|---|---|
| Individualize the patient's dose based on clinical response | ||
| Previously treated children aged ≤12 years | 25–50 IU/kg | 2x/week, 3x/week, or every other day |
INDICATION FOR KOVALTRY®
KOVALTRY® Antihemophilic Factor (Recombinant) is a recombinant human DNA sequence derived, full length Factor VIII concentrate indicated for use in adults and children with hemophilia A for:
On-demand treatment and control of bleeding episodes
Perioperative management of bleeding
Routine prophylaxis to reduce the frequency of bleeding episodes
KOVALTRY is not indicated for the treatment of von Willebrand disease.
IMPORTANT SAFETY INFORMATION
KOVALTRY is contraindicated in patients who have a history of hypersensitivity reactions to the active substance, to any of the excipients, or to mouse or hamster proteins.
Hypersensitivity reactions, including anaphylaxis, are possible with KOVALTRY. Early signs of hypersensitivity reactions, which can progress to anaphylaxis, may include chest or throat tightness, dizziness, mild hypotension and nausea. Discontinue KOVALTRY if symptoms occur and seek immediate emergency treatment.
KOVALTRY may contain trace amounts of mouse and hamster proteins. Patients treated with this product may develop hypersensitivity to these non-human mammalian proteins.
Neutralizing antibody (inhibitor) formation has occurred following administration of KOVALTRY. Previously untreated patients (PUPs) are at greatest risk for inhibitor development with all Factor VIII products. Carefully monitor patients for the development of Factor VIII inhibitors, using appropriate clinical observations and laboratory tests. If expected plasma Factor VIII activity levels are not attained or if bleeding is not controlled as expected with administered dose, suspect the presence of an inhibitor.
Hemophilic patients with cardiovascular risk factors or diseases may be at the same risk to develop cardiovascular events as non-hemophilic patients when clotting has been normalized by treatment with Factor VIII.
Catheter-related infections may occur when KOVALTRY is administered via central venous access devices (CVADs). These infections have not been associated with the product itself.
The most frequently reported adverse reactions in clinical trials (≥5%) were inhibitors in previously untreated patients (PUPs)/minimally treated patients (MTPs), and pyrexia, headache, and rash.
For additional important risk and use information, please see full Prescribing Information.
References: 1. KOVALTRY® [prescribing information]. Whippany, NJ: Bayer HealthCare LLC; 2021. 2. Ljung R, Kenet G, Mancuso ME, et al. BAY 81-8973 safety and efficacy for prophylaxis and treatment of bleeds in previously treated children with severe hemophilia A: results of the LEOPOLD Kids Trial [published online December 9, 2015]. Haemophilia. doi:10.1111/hae.12866. 3. Oldenburg J, Windyga J, Hampton K, et al. Safety and efficacy of BAY 81-8973 for surgery in previously treated patients with haemophilia A: results of the LEOPOLD clinical trial programme. Haemophilia. 2016;22(3):349–353.
You are encouraged to report negative side effects or quality complaints of prescription drugs to the FDA. Visit
www.fda.gov/medwatch or call 1-800-FDA-1088.
©2024 Bayer. All rights reserved.
Bayer, the Bayer Cross, and KOVALTRY are registered trademarks of Bayer.
Access Services by Bayer is a trademark of Bayer.
ADVATE is a registered trademark of Baxalta Incorporated, a Takeda company.
Site Last Modified 06/2024
