JIVI® (antihemophilic factor [recombinant] PEGylated-aucl) Pharmacokinetic Profile Compared to Eloctate® Showed Improved Characteristics in PK Study of Extended Half-life Recombinant FVIII Therapies

WHIPPANY, N.J., Aug. 13, 2019 /PRNewswire/ -- A head-to-head study directly comparing the pharmacokinetic (PK) profiles of two extended half-life (EHL) recombinant factor VIII (FVIII) therapies demonstrated improved PK characteristics for Jivi^® (antihemophilic factor [recombinant] PEGylated-aucl) compared to Eloctate^® (recombinant FVIII fusion protein) in adult patients (n=17) with severe hemophilia A (excluding an outlier patient) who were previously treated with any factor VIII (FVIII) product. The data, which was recently published in the online issue of Annals of Hematology, included a significantly higher area under the curve from time 0 to the last data point (AUC_0-tlast the study's primary parameter) as well as a longer half-life and a slower clearance for Jivi compared to Eloctate.¹

"Our findings also indicated that when compared with Eloctate, we could simulate that Jivi would maintain factor VIII medication levels in the blood for longer periods of time," said Alfonso Iorio, MD, one of the co-authors of the Annals of Hematology paper. "That is a key consideration when selecting a factor VIII medication for a patient with hemophilia A. Sustained maintenance of therapeutic levels provides the ability to offer less frequent dosing," added Dr. Iorio, who is a professor in the Divisions of Hematology and Thromboembolism and General Internal Medicine in the Department of Medicine at McMaster University in Hamilton, Ontario, Canada.

Prophylactic treatment regimens for patients with hemophilia A typically require frequent intravenous infusions. A product's PK profile – its activity in the body over time – is one of several factors physicians consider when determining the appropriate level of infused FVIII for a patient. EHL recombinant FVIII products with improved PK profiles, compared with standard-half-life products, thus have the potential to maintain FVIII levels for longer periods of time, enabling physicians to tailor the prophylactic regimen based on individual patient needs.¹

"As the first trial to directly compare the pharmacokinetics of these two extended half-life recombinant factor VIII medications, this study provides valuable insights for physicians considering this class of therapy for their patients with hemophilia A," said Anita Shah, PhD, senior director, clinical pharmacokinetics at Bayer. "With multiple extended half-life factor VIII therapies available, head-to-head data are increasingly important in helping make more informed treatment decisions."

About the Head-to-Head Study
The phase I, single-dose, open-label crossover study randomized patients aged 18–65 years to a single 60 IU/kg infusion of Jivi (BAY 94-9027) or Eloctate (rFVIIIFc), followed by crossover to a single 60 IU/kg infusion of the other treatment, with a washout period of at least 7 days between treatments. The investigators collected plasma samples pre-dose and up to 120 hours after infusion of each drug. The primary PK endpoint was the area under the curve from time 0 (pre-dose) to the last data point (AUC_0-tlast). Of the 18 patients who were randomized and treated, one was identified as a PK outlier and excluded from the final analysis; this 34-year-old patient with pre-existing anti-PEG antibodies was found to have a significantly reduced AUC_0-tlast with BAY 94-9027, compared with all other patients in the study. Analysis of all 18 patients (including the PK outlier) showed that BAY 94-9027 was non-inferior and not superior to rFVIIIFc for mean AUC_0-tlast. With the outlier excluded, the final analysis demonstrated a 25% higher mean AUC_0-tlast (p = 0.0001), a 20% slower clearance (p = 0.0001), and a 7% longer terminal half-life (p < 0.05) for BAY 94-9027 than for rFVIIIFc. The researchers thus simulated a longer time above the FVIII threshold with BAY 94-9027 than with an equivalent dose of rFVIIIFc¹ in a population PK model excluding the outlier.

About Jivi (antihemophilic factor [recombinant] PEGylated-aucl)
Jivi is a recombinant factor VIII (rFVIII) replacement therapy, meaning it replaces the reduced or missing FVIII (a protein needed to form blood clots) in patients with hemophilia A. Through its site-specific PEGylation, Jivi has a half-life of 17.9 hours that delivers sustained levels in the blood.²

Jivi is approved for the routine prophylactic treatment of hemophilia A in previously treated adults and adolescents 12 years of age or older. Jivi's initial recommended dosing regimen is twice weekly (30-40 IU/kg) with the ability to dose every five days (45-60 IU/kg) and further individually adjust to less or more frequent dosing based on bleeding episodes. The U.S. Food and Drug Administration (FDA) also approved Jivi for on-demand treatment and the perioperative management of bleeding in the same population.²

Jivi Indications and Important Safety Information

INDICATIONS

• Jivi is an injectable medicine used to replace clotting factor (Factor VIII or antihemophilic factor) that is missing in people with hemophilia A.
• Jivi is used to treat and control bleeding in previously treated adults and adolescents (12 years of age and older) with hemophilia A. Your healthcare provider may also give you Jivi when you have surgery. Jivi can reduce the number of bleeding episodes in adults and adolescents with hemophilia A when used regularly (prophylaxis).
• Jivi is not for use in children below 12 years of age or in previously untreated patients.
• Jivi is not used to treat von Willebrand disease.

IMPORTANT SAFETY INFORMATION

• You should not use Jivi if you are allergic to rodents (like mice and hamsters) or to any ingredients in Jivi.
• Tell your healthcare provider about all of your medical conditions that you have or had.
• Tell your healthcare provider if you have been told that you have inhibitors to Factor VIII.
• Allergic reactions may occur with Jivi. Call your healthcare provider right away and stop treatment if you get tightness of the chest or throat, dizziness, decrease in blood pressure, or nausea.
• Allergic reactions to polyethylene glycol (PEG), a component of Jivi, are possible.
• Your body can also make antibodies, called "inhibitors," against Jivi, which may stop Jivi from working properly. Consult your healthcare provider to make sure you are carefully monitored with blood tests for the development of inhibitors to Factor VIII.
• If your bleeding is not being controlled with your usual dose of Jivi, consult your doctor immediately. You may have developed Factor VIII inhibitors or antibodies to PEG and your doctor may carry out tests to confirm this.
• The common side effects of Jivi are headache, cough, nausea, and fever.
• These are not all the possible side effects with Jivi. Tell your healthcare provider about any side effect that bothers you or that does not go away.

For additional important risk and use information, please click on 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.

About Hemophilia A
Hemophilia affects approximately 400,000 people around the world, including an estimated 20,000 in the U.S. today.³ It is a largely inherited disorder in which one of the proteins needed to form blood clots is missing or reduced. In hemophilia A, the most common type of hemophilia, blood clotting is impaired as a result of a lack or defect of coagulation factor VIII. Patients therefore repeatedly experience bleeds in muscles, joints or other tissues, which can result in chronic joint damage.

Hemophilia treatment has advanced considerably over the past decades, with life expectancy for people with hemophilia significantly increasing from about 11.4 years in 1920 to a potentially normal life span today.⁴

About Bayer
Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to benefit people by supporting efforts to overcome the major challenges presented by a growing and aging global population. At the same time, the Group aims to increase its earning power and create value through innovation and growth. Bayer is committed to the principles of sustainable development, and the Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2018, the Group employed around 117,000 people and had sales of 39.6 billion euros. Capital expenditures amounted to 2.6 billion euros, R&D expenses to 5.2 billion euros. For more information, go to www.bayer.us.

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This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer's public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

References

¹ Shah A, Solms A, Wiegmann S, et al. Direct comparison of two extended-half-life recombinant FVIII products: A randomized, crossover pharmacokinetic study in patients with severe hemophilia A. Ann Hematol. 2019 Jun 24. doi: 10.1007/s00277-019-03747-2.
²Jivi® [prescribing information]. Whippany, NJ: Bayer; 2018.
³ Fast Facts (2015, July 15). Retrieved October 19, 2017, from: https://www.hemophilia.org/About-Us/Fast-Facts. 
⁴ Hemophilia and Aging (2014). Retrieved October 19, 2017, from: https://www.hemophilia.org/sites/default/files/document/files/Nurses-Guide-Chapter-17-Aging.pdf.

SOURCE Bayer

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