SELECTED IMPORTANT SAFETY INFORMATION ABOUT KOGENATE FS, KOVALTRY, AND JIVI
KOGENATE FS, KOVALTRY, and JIVI are 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. JIVI is also contraindicated in patients who have a history of hypersensitivity reactions to polyethylene glycol (PEG). ...Continue reading below
Kovaltry®: An unmodified, full length recombinant Factor VIII treatment with a cell bank derived from the Kogenate® FS cell line11
Information on children.
Explore data below on Kogenate FS pediatric patients who transitioned to Kovaltry as part of a clinical trial.
LEOPOLD Kids Clinical Trial (n=51)
Study Design
The multinational, open-label study evaluated efficacy and safety of routine prophylaxis either 2 times per week, 3 times per week, or every other day with Kovaltry in previously treated patients (≤12 years) with severe hemophilia A. The primary efficacy endpoint, ABR within 48 hours after prophylactic infusion, was 0 (0.0; 4.0).2
1.9 Median
ABR
0-12 years
(n=51)
(IQR=0.0; 6.0)2
0-<6 years Median dose: 36.4 IU/kg (range: 21-58 IU/kg)2 | 6-12 years Median dose: 31.8 IU/kg (range: 22-50 IU/kg)2 |
0 inhibitors
in 51 previously treated patients2‡
‡No confirmed cases of neutralizing antibodies (inhibitors) to FVIII occurred.
People with hemophilia A may develop inhibitors to rFVIII.2†
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.
†One 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.2
ABR, annualized bleed rate.
IQR=interquartile range.
†People with a history of inhibitors and previously untreated children were excluded from LEOPOLD Kids.10
Post-hoc subgroup analysis (n=18)
18 pediatric Kogenate FS patients transitioned to Kovaltry prophylaxis as part of the LEOPOLD Kids clinical trial.10
Kogenate FS patients experienced fewer annual bleeds after transitioning to Kovaltry10*
Kogenate FS ABR prior to study enrollment*
1.0
Median ABR
0-12 years (n=18)
(IQR=0.0; 6.0)10
Kovaltry ABR during study
0.0 Median
ABR
0-12 years
(n=18)
(IQR=0.0; 6.02)10
|
0-<6 years (n=11)
Median dose:
34 IU/kg (range: 23 - 56 IU/kg)10 |
6-12 years (n=7)
Median dose:
37.6 IU/kg (range: 23 - 47 IU/kg)10 |
0 inhibitors
in the subgroup analysis of 18 previously treated patients10
People with hemophilia A may develop inhibitors to rFVIII.10*
There were no drug-related adverse events in this subgroup.
ABR, annualized bleed rate.
IQR=interquartile range.
*Self-reported bleeds in prior 12 months.
†People with a history of inhibitors and previously untreated children were excluded from LEOPOLD Kids.9
Kovaltry offers Kogenate FS patients ≤12 years old the opportunity to stay on the same dose and frequency1,2.
| Kogenate FS | Kovaltry | |||
|---|---|---|---|---|
| Dose | 25 IU/kg | 25 IU/kg 50 IU/kg | Potential to stay on the same dose | |
| Frequency | Every other day | Every other day 3x per week 2x per week | Potential to stay on the same infusion frequency or reduce frequency | |
| Kogenate FS | Kovaltry | |
|---|---|---|
| Dose | 25 IU/kg Potential to stay on the same dose | 25 IU/kg 50 IU/kg |
| Frequency | Every other day Potential to stay on the same infusion frequency or reduce frequency | Every other day 3x per week 2x per week |
Kovaltry offers patients currently on Kogenate FS…
- The potential to stay on the same dose and frequency2
- A cell bank derived from the Kogenate FS cell line11
- Advancements to the Kogenate manufacturing process, including2:
- Removal of human and animal derived raw materials from the cell culture
- Addition of 20nm filtration step
In a post hoc subgroup analysis, Kogenate FS patients who transitioned to Kovaltry as part of clinical trials experienced9,10:
- A reduction in ABR*
- Zero inhibitors
- 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.
*Self-reported bleeds in prior 12 months.
For more information on Kovaltry, visit the Kovaltry website.
Click here to go to the Resources page where you can download this information.
1. Kogenate Prescribing Information. Bayer HealthCare LLC, Whippany, NJ. 2. Kovaltry Prescribing Information. Bayer HealthCare LLC, Whippany, NJ; 2016. 8. Data on file. Jivi Protect VIII Subgroup Analysis. Bayer HealthCare LLC, Whippany, NJ. 9. Data on file. Leopold I (12954) prior Kogenate FS/Helixate FS cohort. Bayer HealthCare LLC, Whippany, NJ. 10. Data on file. LEOPOLD Kids Subgroup Analysis. Bayer HealthCare LLC, Whippany, NJ. 11. Data on File. Kovaltry Summary Basis for Regulatory Action. Bayer HealthCare LLC, Whippany, NJ; 2016.
ISI v2 - Important Safety Information v3
Indications and Important Safety Information
Indication For KOGENATE® FS
KOGENATE FS is an Antihemophilic Factor (Recombinant) indicated for:
- On-demand treatment and control of bleeding episodes in adults and children with hemophilia A.
- Perioperative management of bleeding in adults and children with hemophilia A.
- Routine prophylaxis to reduce the frequency of bleeding episodes in children with hemophilia A and to reduce the risk of joint damage in children without pre-existing joint damage.
- Routine prophylaxis to reduce the frequency of bleeding episodes in adults with hemophilia A.
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
Indication For JIVI®
JIVI antihemophilic factor (recombinant), PEGylated-aucl, is a recombinant DNA-derived, Factor VIII concentrate indicated for use in previously treated adults and adolescents (12 years of age and older) with hemophilia A (congenital Factor VIII deficiency) for:
- On-demand treatment and control of bleeding episodes
- Perioperative management of bleeding
- Routine prophylaxis to reduce the frequency of bleeding episodes
Limitations of Use For JIVI:
- JIVI is not indicated for use in children
less than 12 years of age due to a greater risk for hypersensitivity reactions. - JIVI is not indicated for use in previously untreated patients (PUPs).
KOGENATE FS, KOVALTRY, and JIVI are not indicated for the treatment of von Willebrand disease.
Important Safety Information About KOGENATE FS, KOVALTRY, and JIVI
- KOGENATE FS, KOVALTRY, and JIVI are 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. JIVI is also contraindicated in patients who have a history of hypersensitivity reactions to polyethylene glycol (PEG).
- Hypersensitivity reactions, including severe allergic reactions, are possible with KOGENATE FS, KOVALTRY, and JIVI. Monitor patients for hypersensitivity symptoms.
Early signs of hypersensitivity reactions, which can progress to anaphylaxis, may include chest or throat tightness, dizziness, mild hypotension and nausea. Discontinue KOGENATE
FS, KOVALTRY, or JIVI if symptoms occur and seek immediate emergency treatment. - KOGENATE FS, KOVALTRY, and JIVI may contain trace amounts of mouse and hamster proteins. Patients treated with KOGENATE FS, KOVALTRY, or JIVI may develop hypersensitivity to these non-human mammalian proteins.
- Neutralizing antibodies (inhibitors) have occurred following administration of KOGENATE FS, KOVALTRY, and JIVI predominately in previously untreated patients. 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 with an expected dose, suspect the presence of an inhibitor.
- For JIVI, a clinical immune response associated with IgM anti-PEG antibodies, manifested as symptoms of acute hypersensitivity and/or loss of drug effect, has been observed primarily in patients < 6 years of age. The symptoms of the clinical immune response were transient. Anti-PEG IgM titers decreased over time to undetectable levels. No immunoglobulin class switching was observed. In case of clinical suspicion of loss of drug effect, conduct testing for Factor VIII inhibitors and Factor VIII recovery.
- For JIVI, a low post-infusion Factor VIII level in the absence of detectable Factor VIII inhibitors indicates that loss of drug effect is likely due to anti-PEG antibodies. Discontinue JIVI and switch patients to a previously effective Factor VIII product.
- 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.
In clinical trials with:
- KOGENATE FS – the most common adverse reactions (≥4%) observed were inhibitor formation in previously untreated and minimally treated patients, skin-related hypersensitivity reactions, infusion site reactions, and CVAD-associated infections.
- KOVALTRY – 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.
- JIVI – the most frequently (≥5%) reported adverse reactions in previously treated patients (PTPs) ≥12 years of age were headache, cough, nausea, and fever.
For additional important risk and use information, please see the full Prescribing Information for KOGENATE FS, KOVALTRY, and JIVI.
