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
Jivi®: Powerful protection from bleeds with a twice-weekly starting dose and the potential to step up to every 5 days and fine tune3
Jivi is indicated for previously treated patients aged ≥12 years.3
Explore data below on Kogenate® FS patients who transitioned to Jivi as part of a clinical trial.
Jivi Prophylaxis Treatment
Protect VIII Clinical Trial Data (n=110)
Study Design
112 patients entered prophylactic treatment arms. Two patients enrolled in the prophylactic arms left the main study prematurely during the run-in period. 110 patients completed a 10-week run-in period where they received 25 IU/kg twice weekly. They were then assigned or randomized to a treatment arm based on bleeding tendency. Among patients with low bleeding tendencies, 11 received 30-40 IU/kg twice weekly and 43 patients received 45-60 IU/kg every 5 days for 26 weeks. 13 patients with high bleeding tendencies received 30-40 IU/kg twice weekly for 26 weeks.3
Twice-weekly | Every 5 days | Combined3 | |||
Bleeding Tendency3 | LOW* (n=11) | HIGH† (n=13) | LOW* (n=43) | n=67 | |
Total ABR (weeks 10-36)3 | Median ABR (Q1;Q3)3 | 1.9 (0.0; 5.2) | 4.1 (2.0; 10.6) | 1.9 (0.0; 4.2) | 2.1 (0.0; 5.8) |
Mean (SD)3 | 2.2 (2.7) | 7.2‡ (7.5) | 3.3 (4.3) | 3.9 (5.1) | |
Jivi Median (Range) Prophylaxis Dose/Infusion, IU/kg3 | 30.6 (29-41) | 39.2 (33-42) | 45.3 (39-58) | ||
Twice-weekly | |||
Bleeding Tendency3 | LOW* (n=11) | HIGH† (n=13) | |
Total ABR (weeks 10-36)3 | Median ABR (Q1;Q3)3 | 1.9 (0.0; 5.2) | 4.1 (2.0; 10.6) |
Mean (SD)3 | 2.2 (2.7) | 7.2‡ (7.5) | |
Jivi Median (Range) Prophylaxis Dose/Infusion, IU/kg3 | 30.6 (29-41) | 39.2 (33-42) | |
Every 5 days | |||
Bleeding Tendency3 | LOW* (n=43) | ||
Total ABR (weeks 10-36)3 | Median ABR (Q1;Q3)3 | 1.9 (0.0; 4.2) | |
Mean (SD)3 | 3.3 (4.3) | ||
Jivi Median (Range) Prophylaxis Dose/Infusion, IU/kg3 | 45.3 (39-58) | ||
Combined3 | |||
Bleeding Tendency3 | n=67 | ||
Total ABR (weeks 10-36)3 | Median ABR (Q1;Q3)3 | 2.1 (0.0; 5.8) | |
Mean (SD)3 | 3.9 (5.1) | ||
The median Jivi dose per infusion in the overall subject population of PROTECT VIII was within the approved dosing recommendation for the 2x/week arms (30–40 IU/kg) and every-5-day arm (45–60 IU/kg)3
0
inhibitors
in the completed study4
Factor VIII inhibitor (1.7 BU/mL) was reported in one previously treated adult subject. Repeat testing did not confirm the presence of a Factor VIII inhibitor.3
- The most frequently (≥5%) reported adverse reactions in clinical trials in previously treated patients (PTPs) ≥12 years of age were headache, cough, nausea and fever.
- Hypersensitivity reactions were reported in 2 patients. In one patient, the hypersensitivity was related to polyethylene glycol (PEG), a component of Jivi.
ABR, annualized bleed rate.
*Patients with 0 or 1 spontaneous bleed (defined as a joint or muscle bleed and no identified trauma) during weeks 1-10 of the main study.4
†Patients with 2 or more spontaneous bleeds (defined as joint or muscle bleeds and no identified trauma) during weeks 1-10 of the main study.4
‡n=9/13 of these patients were on prior prophylaxis and had a mean number total ABR of 17.4 before entering the main study.
Post-hoc subgroup data analysis (n=21)
21 Kogenate FS prophylaxis patients transitioned to Jivi as part of the Protect VIII clinical trial.8
- 67% of the subgroup were on an every-5-day Jivi regimen.
Kogenate FS patients experienced fewer annual bleeds after transitioning to Jivi8*
| Kogenate FS ABR prior to study enrollment* | Jivi ABR During Study | |||
|---|---|---|---|---|
| Median ABR (Q1;Q3)3
|
9 (1.0; 15.0) | 2.1 (0.0; 10.0) | ||
| Mean (SD)3 | 10.5 (12.3) | 5.2 (7.2) | ||
| Twice-weekly | Every 5 days | |||
| Bleeding Tendency8 | LOW (n=3) | HIGH (n=4) | LOW (n=14) | |
| Jivi Median (Range) Prophylaxis Dose/Infusion, IU/kg8 |
31.4 (29-33) | 41.2 (37-42) | 45.4 (41-54) | |
| Kogenate FS ABR prior to study enrollment* | |
|---|---|
| Median ABR (Q1;Q3)3 |
9 (1.0; 15.0) |
| Mean (SD)3 | 10.5 (12.3) |
| Jivi ABR During Study | |
|---|---|
| Median ABR (Q1;Q3)3 |
2.1 (0.0; 10.0) |
| Mean (SD)3 | 5.2 (7.2) |
| Twice-weekly | ||
|---|---|---|
| Bleeding Tendency8 | LOW (n=3) | HIGH (n=4) |
| Jivi Median (Range) Prophylaxis Dose/Infusion, IU/kg8 |
31.4 (29-33) | 41.2 (37-42) |
|---|---|---|
| Every 5 Days | |
|---|---|
| Bleeding Tendency8 | LOW (n=14) |
| Jivi Median (Range) Prophylaxis Dose/Infusion, IU/kg8 |
45.4 (41-54) |
|---|---|
0
inhibitors
in the subgroup analysis of 21 previously treated patients8
- A drug-related adverse event was reported in one patient. There were no serious drug related adverse events.
ABR, annualized bleed rate.
*Self-reported bleeds in prior 12 months.6
Unique, step-wise dosing with the potential for fewer infusions6,7:
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For patients ≥12 years
|
|
|---|---|
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Start simply
TWICE WEEKLY
|
For all prophylaxis patients: Recommended starting regimen is Jivi twice weekly (30-40 IU/kg)3*
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Step up
EVERY 5 DAYS
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Based on bleeding episodes: Less frequent dosing of Jivi every 5 days (45-60 IU/kg) can be used3*
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Fine tune
|
Based on bleeding episodes: The dosing frequency may be further adjusted up or down3
|
*100% of patients in the every-5-days and twice-weekly dosing arms remained on the same dosing regimen for the duration of the main study.3
Jivi offers adolescent and adult prophylaxis patients currently on Kogenate FS...
Powerful protection from bleeds with a twice-weekly starting dose and, based on bleeding episodes, the potential to step up to every 5 days and fine tune3
A demonstrated safety profile in previously-treated asolescents and adults4,6
The potential for fewer infusions5:
- 8/10 patients in the PROTECT VIII main study reduced dosing frequency vs their pre-study prophylaxis regimen
In a post hoc subgroup analysis, Kogenate FS patients who transitioned to Jivi prophylaxis as part of a clinical trial experienced8-10:
- A reduction in ABR*
- Zero inhibitors
67% of the subgroup were on an every-5-day Jivi regimen
- The most frequently (≥5%) reported adverse reactions in clinical trials in previously treated patients (PTPs) ≥ 12 years of age were headache, couch, nausea, and fever.
- Allergic reactions occurred in 2 patients. In 1 patient, the allergic reaction was related to polyethlylene glycol (PEG), a component of Jivi.
*Self-reported bleeds in prior 12 months.8-10
Jivi On-Demand Treatment
PROTECT VIII Clinical Trial (N=20)
The safety and efficacy of Jivi for on-demand treatment in adolescent and adult (12 to 65 years of age) previously treated patients (PTPs) was evaluated for 36 weeks.3,13
Jivi table efficacy - tab 3 circle
91.2%
of bleeds were treated
with ≤2 infusions13
79.5%
1 infusion13
11.7%
2 infusions13
8.8%
3+ infusions13
40.4% of total bleeds were trauma bleeds.13
0 inhibitors
in the main study analysis of 20 previously treated patients.13
One patient in the on-demand group (n=20) experienced mild drug-related adverse events (dry mouth, musculoskeletal discomfort).13
The on-demand arm in the Protect VIII clinical trial and the subgroup analysis both included patients with Hepatitis B, Hepatitis C, and HIV.14
Subgroup analysis (n=10)
10 Kogenate FS on-demand patients transitioned to Jivi on-demand as part of the clinical trial.13
Jivi table efficacy - tab 4 circle
90.6%
of bleeds were treated
with ≤2 infusions13
73.9%
1 infusion13
16.7%
2 infusions13
9.4%
3+ infusions13
36.0% of total bleeds were trauma bleeds.13
0 inhibitors
in the subgroup analysis of 10 previously treated patients.13
One patient in the on-demand subgroup (n=10) experienced mild drug-related adverse events (dry mouth, musculoskeletal discomfort).14
The on-demand arm in the Protect VIII clinical trial and the subgroup analysis both included patients with Hepatitis B, Hepatitis C, and HIV.14
Jivi offers adolescent and adult on-demand patients currently on Kogenate FS...
- Effective treatment of bleeds6,8
- A proven safety profile6,8
In a post hoc subgroup analysis, Kogenate FS patients who transitioned to Jivi on-demand treatment as part of a clinical trial experienced13:
- 90.6% of bleeds treated with ≤2 infusions
- Zero inhibitors
- The most frequently (≥5%) reported adverse reactions in clinical trials in previously treated patients (PTPs) ≥12 years of age were headache, cough, nausea, and fever.
- One patient in the on-demand subgroup (n=10) experienced mild drug-related adverse events (dry mouth, musculoskeletal discomfort).14
For more information and data on patients who participated in the Jivi extension study, and to see additional Jivi PK data, including how Jivi compares to other EHLs, visit the Jivi website.
Click here to go to the Resources page where you can download this information.
3. Jivi Prescribing Information. Bayer HealthCare LLC, Whippany, NJ; 2018. 4. Reding MT et al. J Thromb Haemost 2017;15:411-419. 5. Kerlin BA et al. Poster P153. Presented at the 4th Biennial Summit of the Thrombosis & Haemostasis Societies of North America. March 8-10, 2018, San Diego, California. 6. Lalezari S et al. Haemophilia 2019;25:1011-1019. 7. Data on file. Tx Review 0918, Bayer; 2018. 8. Data on file. Jivi Protect VIII Subgroup Analysis. Bayer HealthCare LLC, Whippany, NJ. 13. Data on file. Protect VIII (13024) prior OD Kogenate FS/Helixate FS Cohort Descriptive Analysis. 14. Data on file. Jivi Protect FVIII (13024) Subgroup- prior 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.
