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 for adolescent and adult patients.
Explore data below on Kogenate FS patients who transitioned to Kovaltry as part of a clinical trial.
Kovaltry Prophylaxis Treatment
LEOPOLD I Clinical Trial (n=62)
Study Design
The multinational, open-label prospective study of previously treated patients aged 12-65 years with severe hemophilia A evaluated efficacy and safety of Kovaltry 2x/week (n=18) or 3x/week (n=44) prophylaxis. The primary efficacy endpoint was annualized bleed rate (ABR) at 12 months.2
1 Median
ABR
(n=62)
(IQR=0.0; 5.1)12
Median dose:
31.2 IU/kg
(range: 21-43 IU/kg)12
0 inhibitors
in 62 previously treated patients2
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.
ABR, annualized bleed rate.
IQR=interquartile range.
*People with a history of inhibitors were excluded from LEOPOLD I9
Post-hoc subgroup analysis (n=22)
22 adolescent and adult Kogenate FS patients transitioned to Kovaltry prophylaxis as part of the LEOPOLD I clinical trial.9
Kogenate FS patients experienced fewer annual bleeds after transitioning to Kovaltry9†
Kogenate FS ABR prior to study enrollment*†
2.5
Median ABR
(n=22)
(IQR=0.0; 9.0)9
Kovaltry ABR during study
1
Median
ABR
(n=22)
(IQR=0.0; 6.8)9
Median dose:
35.4 IU/kg
(range: 23.99-49.26)9
0 inhibitors
in the subgroup analysis of 22 previously treated patients9
People with hemophilia A may develop inhibitors to rFVIII.9‡
There were no drug-related adverse events in this subgroup during the 12 months of the main trial.
ABR, annualized bleed rate.
IQR=interquartile range.
*Prior Kogenate FS or Helixate FS dose not calculated or not available.9
†Self-reported bleeds in prior 12 months.9
‡People with a history of inhibitors were excluded from LEOPOLD I.9
Kovaltry offers adult and adolescent Kogenate FS patients the opportunity to stay on the same dose and frequency1,2.
| Kogenate FS | Kovaltry | |||
|---|---|---|---|---|
| Dose |
25 IU/kg
|
20 IU/kg 40 IU/kg | Potential to stay on the same dose | |
|
|
||||
| Frequency |
3x per week
|
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 | 20 IU/kg 40 IU/kg |
| Frequency | 3x per week Potential to stay on the same infusion frequency or reduce frequency | 3x per week 2x per week |
Kovaltry offers prophylaxis 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 prophylaxis as part of clinical trial experienced8-10:
- 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.9
Kovaltry On-Demand Treatment
LEOPOLD II Clinical Trial (N=21)
The safety and efficacy of Kovaltry for on-demand treatment in adolescent and adult (12 to 65 years of age) previously treated patients (PTPs) was evaluated for 12 months2,15
kovaltry adults - tab 3 circle - eficacy draw
95.2%
of bleeds were treated
with ≤2 infusions15
75.5%
1 infusion15
19.7%
2 infusions15
4.8%
3+ infusions15
21.6% of total bleeds were trauma bleeds.15
0 inhibitors
in the main study analysis of 21 previously treated patients.15
One patient in the on-demand group (n=21) experienced a mild drug-related adverse event (infusion site pruritus).15
The on-demand arm in the LEOPOLD II clinical trial and the subgroup analysis both included patients with Hepatitis B, Hepatitis C, and HIV.15
Subgroup analysis (n=10)
10 Kogenate FS on-demand patients transitioned to Kovaltry on-demand as part of the clinical trial.15
kovaltry adults - tab 4 - circle eficacy transitioned draw
96.7%
of bleeds were treated
with ≤2 infusions15
85.9%
1 infusion15
10.8%
2 infusions15
3.3%
3+ infusions15
15.9% of total bleeds were trauma bleeds.15
0 inhibitors
in the subgroup analysis of 10 previously treated patients.15
There were no drug-related adverse events in the subgroup.16
The on-demand arm in the LEOPOLD II clinical trial and the subgroup analysis both included patients with Hepatitis B, Hepatitis C, and HIV.15
Kovaltry offers on-demand patients currently on Kogenate FS…
- 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 on-demand as part of a clinical trial experienced15:
- 96.7% of bleeds treated with ≤2 infusions
- Zero inhibitors
- There were no drug-related adverse events in this subgroup.16
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; 2021. 9. Data on file. Leopold I (12954) prior Kogenate FS/Helixate FS cohort. Bayer HealthCare LLC, Whippany, NJ; 2016. 11. Data on File. Kovaltry Summary Basis for Regulatory Action. Bayer HealthCare LLC, Whippany, NJ; 2016. 12. Saxena K, Lalezari S, Oldenburg J, et al. Efficacy and safety of BAY 81-8973, a full-length recombinant factor VIII: results from the LEOPOLD I trial. Haemophilia. 2016;22(5):706-712. 15. Data on file. Leopold II (14319) prior OD Kogenate FS/Helixate FS Cohort - Descriptive Analysis. Bayer Healthcare LLC, Whippany, NJ. 16. Data on file. Leopold II (14319) prior OD Kogenate FS/Helixate FS Cohort. Bayer HealthCare LLC, Whippany, NJ.
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.
