title: Safety and efficacy of BAY 94-9027, a prolonged-half-life factor VIII.
abstract: Essentials Recombinant factor VIII BAY 94-9027 conjugates in a site-specific manner with polyethylene glycol. BAY 94-9027 was given to patients with severe hemophilia A as prophylaxis and to treat bleeds. BAY 94-9027 prevented bleeds at dose intervals up to every 7 days and effectively treated bleeds. BAY 94-9027 treatment was mainly well tolerated and no patient developed factor VIII inhibitors. Click to hear Dr Tiede's perspective on half-life extended factor VIII for the treatment of hemophilia A SUMMARY: Background BAY 94-9027 is a B-domain-deleted prolonged-half-life recombinant factor VIII (FVIII) that conjugates in a site-specific manner with polyethylene glycol. Objective Assess efficacy and safety of BAY 94-9027 for prophylaxis and treatment of bleeds in patients with severe hemophilia A. Patients/methods In this multinational, phase 2/3, partially randomized, open-label trial, men aged 12-65 years with FVIII < 1% and ≥ 150 exposure days to FVIII received BAY 94-9027 for 36 weeks on demand or prophylactically at intervals determined following a 10-week run-in period on 25 IU kg-1body weight two times per week. Patients with > 1 bleed during the run-in subsequently received 30-40 IU kg-1two times per week; patients with ≤ 1 bleed were eligible for randomization to every-5-days (45-60 IU kg-1) or every-7-days (60 IU kg-1) prophylaxis (1 : 1) for 26 additional weeks until randomization arms were filled. Patients who were eligible but not randomized continued twice-weekly prophylaxis. The primary efficacy outcome was annualized bleeding rate (ABR). Results The intent-to-treat population included 132 patients (prophylaxis, n = 112; on demand, n = 20). Median ABR (quartile [Q1; Q3]) for patients treated two times per week who were not eligible for randomization (n = 13) improved after dose increase (17.4 [14.3; 26.0] to 4.1 [2.0; 10.6]). Median ABR for patients randomized to every-5-days treatment (n = 43) was 1.9 (0; 4.2), similar to patients eligible for randomization but who continued treatment two times per week (n = 11). Median ABR for 32/43 patients (74%) who continued every-7-days prophylaxis until study end was 0.96 (0.0; 4.3). Six hundred and thirty-six of 702 bleeds (90.6%) were controlled with ≤ 2 infusions. No patient developed a FVIII inhibitor. Conclusions BAY 94-9027 prevented bleeding across three individually tailored dose regimens and was effective for treatment of bleeds.
authors.affiliation: University of Minnesota Medical Center, Minneapolis, MN, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Reding
authors.affiliation: Department of Haematology, Singapore General Hospital, Singapore.
authors.forename: H J
authors.initials: HJ
authors.lastname: Ng
authors.affiliation: Centre for Haemophilia and Thrombosis, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: L H
authors.initials: LH
authors.lastname: Poulsen
authors.affiliation: Penn State Hershey Medical Center, Hershey, PA, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Eyster
authors.affiliation: Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Pabinger
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, School of Medicine, Medical Research Institute, Pusan National University Hospital, Busan, Korea.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Shin
authors.affiliation: Bayer Vital GmbH, Leverkusen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Walsch
authors.affiliation: Bayer, Whippany, NJ, USA.
authors.forename: M
authors.initials: M
authors.lastname: Lederman
authors.affiliation: Bayer, Whippany, NJ, USA.
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hardtke
authors.affiliation: Bayer, Whippany, NJ, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Michaels
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001835:Body Weight; D002648:Child; D004334:Drug Administration Schedule; D005169:Factor VIII / Q000494:pharmacology*; D006207:Half-Life; D006467:Hemophilia A / Q000188:drug therapy*; D006470:Hemorrhage / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D011092:Polyethylene Glycols / Q000494:pharmacology*; D000072417:Protein Domains; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C000594952:BAY 94-9027; D011092:Polyethylene Glycols; C078147:F8 protein, human; D005169:Factor VIII
keywords: clinical trial; factor VIII; hemophilia A; prophylaxis; recombinant proteins