SELECTED IMPORTANT SAFETY INFORMATION: Jivi is contraindicated in patients who have a history of hypersensitivity reactions to the active substance, polyethylene glycol (PEG), mouse or hamster proteins, or other constituents of the product. CONTINUE READING BELOW

Jivi® (antihemophilic factor (recombinant) PEGylated-aucl) logo

SELECTED IMPORTANT SAFETY INFORMATION: Jivi is contraindicated in patients who have a history of hypersensitivity reactions to the active substance, polyethylene glycol (PEG), mouse or hamster proteins, or other constituents of the product. CONTINUE READING BELOW

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Protect VIII Main and Extension Studies

The PROTECT VIII main and extension studies were designed to reflect real-world treatment1,2


Patients completing the PROTECT VIII main study were invited to continue on to the extension study.2 Patients on a prophylaxis regimen could continue their current regimen or switch to another dosing regimen on entry to the extension study and at any point during it.

PROTECT VIII main study design3

Chart with data of Protect VIII main study design

Long-term extension study design2

Chart with data of Protect VIII main study design

112 patients entered prophylactic treatment arms; an additional 20 patients entered a control arm of on-demand treatment. Two patients in the prophylactic arms left the main study prematurely during the run-in period.3

Defined as joint or muscle bleeds and no identified trauma.1,3

121 of 134 patients included in the main PROTECT VIII trial continued in the extension study, receiving either on-demand treatment (n=14) or prophylaxis (n=107).2

Patients who switched dosing frequency at least once after the first week of the extension study were analyzed in a separate variable-frequency group.2


In the PROTECT VIII main study: Effective bleed protection with Jivi®3

Chart displaying bleeding tendency data with Protect VIII main study including ABR and spontaneous ABR with Jivi
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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.1

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.1

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.3

ABR, annualized bleed rate.

In the PROTECT VIII long-term extension study: ABRs assessed with Jivi2

While there were no predetermined efficacy objectives in the extension study, bleeding episodes were documented during the routine course of treatment

Chart depicting the ABRs with Jivi in the Protect VIII long-term extension study
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Patients who switched dosing frequency at least once after the first week of the extension study were analyzed in a separate, variable-frequency group.2

ABR, annualized bleed rate.


In the PROTECT VIII main study: Percent of patients with zero total bleeds in the prophylaxis arms with Jivi3,5

Bar chart of the percentage of patients with zero total bleeds in the prophylaxis arms with Jivi in the Protect VIII main study

Total bleeds include spontaneous bleeds, trauma bleeds, and joint bleeds.


Jivi provided effective treatment of bleeds3

Pie chart with percentage of the treated bleeds that occurred during the main study resolved with ≤2 infusions of Jivi (n=112 on prophylaxis)

Treatment of bleeds from week 0 through week 36.3

Two patients discontinued after a single dose of Jivi and were not included in the efficacy analysis.3


During the PROTECT VIII main and extension studies: Target-joint resolution with Jivi6

Results from a post hoc analysis of target-joint status in 82 patients in the prophylactic group from baseline through the main study and into the extension period (median time of 1421 days [range: 700-2071]6)

Pie chart with 95% of historic target joints resolved

107 of 113 historic target joints were resolved at time of analysis (data cutoff 8/28/2019)6

The median (IQR) target joint ABR was 0 (0-1.5) at the end of the main study and 0 (0-1.4) at the extension cutoff date (8/28/2019)6

The mean (SD) target joint ABR was 1.28 (2.14) at the end of the main study and 1.06 (2.08) at the extension cutoff date (8/28/2019)7

Analysis consisted of6:

  • Numbers of historic target joints, as judged by the investigator, recorded at study entry
  • Numbers of resolved target joints (≤2 spontaneous bleeds during last 12 months)
Pie chart with 91% of historic or new target joints were resolved

111 of 122 historic or new target joints were resolved at time of analysis (data cutoff 8/28/2019)6

The median (IQR) target joint ABR was 0 (0-1.5) at the end of the main study and 0 (0-1.4) at the extension cutoff date (8/28/2019)6

The mean (SD) target joint ABR was 1.28 (2.14) at the end of the main study and 1.06 (2.08) at the extension cutoff date (8/28/2019)7

Analysis consisted of6:

  • Numbers of historic target joints, as judged by the investigator, recorded at study entry
  • Numbers of new target joints that developed on-study (≥3 spontaneous bleeds within 6 months)
  • Numbers of resolved target joints (≤2 spontaneous bleeds during last 12 months)

Patients remaining on the same prophylaxis regimen during the last 90 days of treatment. Median (Q1; Q3) joint ABRs were 0.00 (0.0; 8.1) for twice-weekly and 0.00 (0.0; 4.1) for every-5-day final on-study dosing interval.8

As defined by the International Society of Thrombosis and Hemostasis (ISTH).6


During the PROTECT VIII main and extension studies: Long-term safety data with Jivi1,2

Up to 7 years of safety and tolerability data in previously treated adolescents and adults (N=134 in main study; N=121 in extension study)1,2

Image of a loud speaker emitting sound waves

Most common adverse events: headache, cough, nausea, and fever3

Icon of a circle with check mark

Incidence of drug-related AEs/SAEs in the long-term extension study2*

  • Drug-Related AEs: 8.3% (n=10); Drug-Related SAEs: 1.7% (n=2)
Zero number icon

Zero FVIII inhibitors1,2

  • No confirmed case of inhibitors against FVIII occurred
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No confirmed increasing plasma PEG levels over time2,9‡

Icon depicting two people

Hypersensitivity reactions were transient (n=2/134)1

  • Allergic reactions occurred in two patients in the PROTECT VIII main study; one was related to PEG, a component of Jivi1,3
  • No hypersensitivity reactions were reported in the long-term extension study2

Overall AEs: 79.3% (n=96).2

In the main study 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.1

A few patients had transiently detectable PEG just above the lower limit of quantitation (LLOQ). One patient had detectable PEG in plasma only at the last visit of the study, and in accordance with the study protocol, further follow-up was not allowed.2

AE, adverse event; PEG, polyethylene glycol; SAE, serious adverse event.


In the PROTECT VIII main study: Median Jivi doses were within recommended label dosing3*

Chart displaying median Jivi doses within recommended label dosing

Patients received prophylactic therapy for 26 weeks after a 10-week run-in period of twice-weekly 25 IU/kg. Patients that had high bleeding tendency (>1 breakthrough bleeds during the run-in) continued on twice-weekly 30-40 IU/kg. Patients with ≤1 breakthrough bleeds during the run-in were randomized to less frequent dosing of every 5 days (45-60 IU/kg) or every 7 days. After randomization groups were full, remaining eligible patients continued with twice-weekly 30-40 IU/kg.1

In the PROTECT VIII long-term extension study: Median Jivi doses were within recommended label dosing2,3

Chart displaying median Jivi doses within recommended label dosing

Patients received prophylactic therapy for 26 weeks after a 10-week run-in period of twice-weekly 25 IU/kg. Patients that had high bleeding tendency (>1 breakthrough bleeds during the run-in) continued on twice-weekly 30-40 IU/kg. Patients with ≤1 breakthrough bleeds during the run-in were randomized to less frequent dosing of every 5 days (45-60 IU/kg) or every 7 days. After randomization groups were full, remaining eligible patients continued with twice-weekly 30-40 IU/kg.1

Patients who switched at least once after the first week of the extension study were analyzed in a separate variable frequency group.2

INDICATIONS

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:

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).

Jivi is not indicated for the treatment of von Willebrand disease.

IMPORTANT SAFETY INFORMATION

Jivi is contraindicated in patients who have a history of hypersensitivity reactions to the active substance, polyethylene glycol (PEG), mouse or hamster proteins, or other constituents of the product.

Hypersensitivity reactions, including severe allergic reactions, have occurred with 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. If hypersensitivity reactions occur, immediately discontinue administration and initiate appropriate treatment.

Jivi may contain trace amounts of mouse and hamster proteins. Patients treated with this product may develop hypersensitivity to these non-human mammalian proteins.

Hypersensitivity reactions may also be related to antibodies against polyethylene glycol (PEG).

Neutralizing antibody (inhibitor) formation can occur following administration of Jivi. 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 (neutralizing antibody).

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. 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.

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.

For additional important risk and use information, please see the full Prescribing Information.

You are encouraged to report side effects or quality complaints of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call
1-800-FDA-1088.

INDICATIONS

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:

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).

Jivi is not indicated for the treatment of von Willebrand disease.

IMPORTANT SAFETY INFORMATION

Jivi is contraindicated in patients who have a history of hypersensitivity reactions to the active substance, polyethylene glycol (PEG), mouse or hamster proteins, or other constituents of the product.

Hypersensitivity reactions, including severe allergic reactions, have occurred with 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. If hypersensitivity reactions occur, immediately discontinue administration and initiate appropriate treatment.

Jivi may contain trace amounts of mouse and hamster proteins. Patients treated with this product may develop hypersensitivity to these non-human mammalian proteins.

Hypersensitivity reactions may also be related to antibodies against polyethylene glycol (PEG).

Neutralizing antibody (inhibitor) formation can occur following administration of Jivi. 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 (neutralizing antibody).

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. 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.

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.

For additional important risk and use information, please see the full Prescribing Information.

You are encouraged to report side effects or quality complaints of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

References: 1. Reding MT et al. J Thromb Haemost 2017;15:411-419. 2. Reding M, et al. Haemophilia. 2021; 10.1111/hae.14297.​​​​​​​ 3. Jivi Prescribing Information. August 2018. Bayer. 4. Data on file. CSR 13024-A. Bayer; 2018. 5. Data on file. CSR PH 40454. BAY 94-9027/13024. 6. Reding MT et al. Haemophilia. 2020;26(4):e201-e204. 7. Data on file. Jivi PROTECT VIII Extension AUG 2019 CSR Target Joint Analysis data; Bayer. 8. Reding MT et al. Poster P29. Presented at the Hemostasis and Thrombosis Research Society 2019 Scientific Symposium. 9-11 May 2019, New Orleans, Louisiana. 9. Data on file. CSR 2.7.4. Bayer; 2018.