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: Adolescents and Adults
Study design for LEOPOLD I
| LEOPOLD I Trial: Adolescents and Adults1,2 | |
|---|---|
| Study description | Multinational, open-label, prospective trial evaluating pharmacokinetics, efficacy, safety, and perioperative management of bleeding with KOVALTRY® Previously treated male patients (PTPs) aged 12–65 years with severe hemophilia A (<1% FVIII) (N=73) studied for 1 year |
| Dosing | Dosing regimens were determined by the investigators to meet individual patients' needs 2x/week prophylaxis: 20–50 IU/kg (n=18)3x/week prophylaxis: 20–50 IU/kg (n=44) |
| Primary efficacy endpoint | Annualized bleed rate (ABR) at 12 months (n=62 for efficacy analysis) |
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.
Dosing and regimen determined by investigators for LEOPOLD I patients2
Baseline characteristics of LEOPOLD I patients2
| 2x/week dosing (n=18) Median (range) | 3x/week dosing (n=44) Median (range) | |
|---|---|---|
| Age, years | 40 (12–61) | 29 (12–60) |
| Number of target joints | 1 (0–3) | 1 (0–5) |
| Number of bleeds in last 12 months (previous on-demand patients) | 18 (0–36) | 41.5 (6–55) |
| Number of bleeds in last 12 months (previous prophylaxis patients) | 3.5 (0–37) | 4.5 (0–40) |
| Number of joint bleeds in last 12 months | 2 (0–35) | 4 (0–55) |
| n (%) | n (%) | |
|---|---|---|
| Target joint present | 10 (55.6) | 34 (77.3) |
| Previous treatment | ||
| On demand | 2 (11.1) | 10 (22.7) |
| Prophylaxis | 16 (88.9) | 34 (77.3) |
| Median dose per regimen in LEOPOLD I1 | 2x/week dosing (n=18) | 3x/week dosing (n=44) |
|---|---|---|
| Median (range) | 35.0 IU/kg (21–42 IU/kg) | 31.1 IU/kg (24–43 IU/kg) |
| KOVALTRY® dosing for routine prophylaxis1 | 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 |
| Adolescents and adults | 20–40 IU/kg | 2x/week or 3x/week |
Pharmacokinetic activity
Half-life measured via chromogenic and one-stage assays1
Pharmacokinetic activity was tested after a single 50 IU/kg dose of KOVALTRY® in previously treated adolescent and adult patients who have severe hemophilia A.
| Half-life (arithmetic mean ± SD) | ||
|---|---|---|
| 12–17 years (n=5) | ≥18 years (n=21) | |
| One-stage assay | 11.7 ± 1.1 hours | 14.3 ± 3.7 hours |
| Chromogenic assay | 14.4 ± 5.5 hours | 14.2 ± 3.5 hours |
Learn about additional PK parameters for KOVALTRY®, including PK data vs Advate® >
Proven efficacy and safety in adolescents and adults with KOVALTRY®1
ABR by dosing regimen
Dosing was investigator determined to meet individual patients' needs.
IQR=interquartile range.
rFVIII=recombinant Factor VIII.
People with hemophilia A may develop inhibitors to rFVIII. People with a history of inhibitors were excluded from LEOPOLD I1
On-demand bleed treatment in adolescents and adults with KOVALTRY®1
During the 1-year study period
of bleeding episodes were resolved with ≤2 infusions of KOVALTRY®.1
Treatment with KOVALTRY® during surgery1
A total of 44 previously treated patients with severe hemophilia A (43 of whom were adolescents and adults) underwent a total of 14 major and 46 minor surgeries
All subjects received KOVALTRY® as bolus infusions
In the adolescent and adult subjects, initial KOVALTRY® doses administered ranged between 3000–5000 IU
Median total dose on the day of surgery was 107.5 IU/kg (range, 60–207 IU/kg)
Treatment with KOVALTRY® was assessed as good or excellent in all documented surgeries1
Recommended dosing in adolescents and adults
| KOVALTRY® dosing for routine prophylaxis1 | Recommended prophylaxis dose | Regimen |
|---|---|---|
| Individualize the patient's dose based on clinical response | ||
| Adolescents and adults | 20–40 IU/kg | 2x/week or 3x/week |
Mean number of prophylaxis infusions per patient per year
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. Data on file. Bayer HealthCare Pharmaceuticals, Inc; 2016.
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.
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Site Last Modified 06/2024
