Type of information: Granting of a Market Authorisation in Japan
Product name: Jivi® (BAY94-9027)
Compound: recombinant human factor VIII (rFVIII) - damoctogog alfa pegol
Therapeutic area: Rare diseases - Genetic diseases - Hematological diseases
- protein/replacement therapy. BAY94-9027 is engineered to extend the circulating half-life while preserving full biologic activity through site-specific pegylation. This site-specific pegylation is achieved by inserting a single cysteine (amino acid) on the factor VIII surface, which serves as an attachment site for a polyethylene glycol (PEG) polymer.
Company: Bayer (Germany)
Disease: hemophilia A
- • On September 21, 2018, Bayer announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Jivi® (BAY94-9027) for the prophylactic treatment of hemophilia A for adults and adolescents 12 years of age or older in Japan. The recommended usual dose for prophylactic regimens is twice weekly. Jivi® can also be dosed once every 5 days or once a week in accordance with the patient’ conditions. Jivi® is also approved for on-demand treatment and perioperative management of surgeries.
- Jivi® is a site-specifically PEGylated recombinant Factor VIII (rFVIII) that delivers higher sustained levels of FVIII, which extends the blood’s ability to coagulate for longer.
- The approval of Jivi® in Japan is supported by the results of the pivotal Phase 2/3 PROTECT VIII trial where Jivi® showed protection from bleeds with dosing intervals when used prophylactically twice per week, once every five days, and once a week in previously treated adults and adolescents 12 years of age or older with severe hemophilia A. Jivi® is also approved for on-demand treatment and the perioperative management of bleeding in the same population.
- The trial demonstrated that 74 per cent of people with hemophilia A participating in the trial and randomized to treatment of BAY94-9027 once weekly and all (100 per cent) participants receiving treatment once every five days achieved good bleed protection. The patients who maintained on the once weekly regimen in the study had a median annualised bleed rate (ABR) of 0.96; half of them experienced 0 bleeds. Treatment with BAY94-9027 was generally well tolerated both prophylactically and on-demand.
- • On September 20, 2018, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive
opinion, recommending the granting of a marketing authorisation for Jivi®, intended for the treatment of haemophilia A (congenital factor VIII deficiency). Jivi® will be available as powder and solvent for solution for injection (250 IU, 500 IU, 1000 IU, 2000 IU and 3000 IU).
The most common side effects are hypersensitivity, insomnia, headache, dizziness, cough, abdominal pain, nausea,
vomiting, erythema, rash, infusion site reactions and pyrexia.
The full indication is: “Treatment and prophylaxis of bleeding in previously treated patients ? 12 years of
age with haemophilia A (congenital factor VIII deficiency).” The CHMP recommendation is based on results from the Phase 2/3 PROTECT VIII trial.
- • On August 29, 2018, the FDA has approved Jivi® (BAY94-9027) for the routine prophylactic treatment of hemophilia A in previously treated adults and adolescents 12 years of age or older in the U.S. The recommended initial prophylactic regimen for Jivi® is twice weekly, with the ability to dose every five days and further individually adjust to less or more frequent dosing based on bleeding episodes. The FDA also approved Jivi® for on-demand treatment and the perioperative management of bleeding in the same population. This approval is based on results from the Phase 2/3 PROTECT VIII trial. Jivi® is the third FDA-approved hemophilia A treatment in Bayer’s hemophilia portfolio.
Jivi is a rFVIII replacement therapy, meaning it replaces the reduced or missing FVIII in adults and adolescents 12 years of age or older with hemophilia A. As a site-specifically PEGylated FVIII, Jivi has a half-life of 17.9 hours that delivers sustained levels in the blood. rFVIII replacement therapy is the standard of care to stop or prevent bleeding and has proven efficacy and safety established over decades of clinical trials and real-world experiences.
- The FDA approval of Jivi is supported by results of the pivotal Phase 2/3 PROTECT VIII trial comprised of prophylactic dosing, on-demand treatment, and perioperative management in previously treated adults and adolescents 12 years of age or older with severe hemophilia A. The PROTECT VIII study was a 36-week, international, open label trial. Overall 126 patients completed the main study. Part A evaluated pharmacokinetics, efficacy and safety of Jivi for on-demand treatment of bleeds and for prophylactic therapy at different dosing regimens. An optional extension study was available to subjects who completed Part A to assess Jivi® over at least 100 accumulated exposure days, which demonstrated bleed protection and a good safety profile of up to a median of 1.9 years (range of 0-2.6 years). Part B evaluated safety and efficacy of Jivi® during major surgery. Treatment with BAY94-9027 was generally well tolerated.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2018-08-29
Favourable opinion UE: 2018-09-20
Favourable opinion USA:
Orphan status USA:
Orphan status UE: 2011-02-23
Pediatric exclusivit _USA:
Pediatric exclusivity UE: