scholarly journals Advancing personalized care in hemophilia A: ten years’ experience with an advanced category antihemophilic factor prepared using a plasma/albumin-free method

2014 ◽  
pp. 115 ◽  
Author(s):  
Erik Berntorp ◽  
Gerald Spotts ◽  
Lisa Patrone ◽  
Bruce Ewenstein
Keyword(s):  
Hemophilia A ◽  
Plasma Albumin ◽  
Personalized Care ◽  
Antihemophilic Factor

scholarly journals Pharmacokinetic Parameter Driven Outcomes Model Predicts a Reduction in Bleeding Events Associated with BAY 81-8973 Versus Antihemophilic Factor (Recombinant) Plasma/Albumin- Free Method in a Chinese Healthcare Setting

2022 ◽  
Author(s):  
Rong Chen ◽  
Dmitry Gultyaev ◽  
Johanna Lister ◽  
Rong Han ◽  
Nan Hu ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Cost Savings ◽  
Standard Of Care ◽  
Healthcare Setting ◽  
Bleeding Events ◽  
Plasma Albumin ◽  
Lifetime Horizon ◽  
Life Years ◽  
Antihemophilic Factor

Abstract Background: Long-term prophylactic therapy is considered the standard of care for hemophilia A patients. This study models the long-term clinical and cost outcomes of two factor VIII (FVIII) products using a pharmacokinetic (PK) simulation model in a Chinese population. Methods: Head-to-head PK profile data of BAY 81-8973 (KOVALTRY®) and antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM, ADVATE®) were applied to a two-state (alive and dead) Markov model to simulate blood FVIII concentrations at a steady state in prophylactically-treated patients with hemophilia A. Worsening of the Pettersson score was simulated and decline was associated with the probability of having orthopaedic surgery. The only difference between the compounds was FVIII concentration at a given time; each subject was treated with 25 IU/kg every 3 days. The model used a lifetime horizon, with cycle lengths of 1 year. Results: Cumulative bleeding events, joint bleeding events, and major bleeding events were reduced by 19.3%, 9.3% and 19.3%, respectively for BAY 81-8973 compared to rAHF-PFM. Hospitalizations and hospitalization days were also reduced by 19.3% for BAY 81-8973 compared to rAHF-PFM. BAY 81-8973 resulted in both cost savings and a gain in quality adjusted life years (QALYs) compared to rAHF-PFM. Conclusion: Based on modeled head-to-head comparisons, differences in PK-properties between BAY 81-8973 and rAHF-PFM result in a reduced number of bleeding events, leading to reduced costs and increased quality of life for BAY 81-8973. These results should be used to inform clinical practice in China when caring for patients with severe hemophilia A.

Safety and Efficacy Profile of rAHF-PFM for Immune Tolerance Induction as Assessed In 3 Clinical Trials (PUP ITI, PRE-PAIR, and PAIR).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3670-3670
Author(s):  
Gerald Spotts ◽  
Brigitt E. Abbuehl ◽  
Huong D. Luu ◽  
Clara K. Song ◽  
Jacqueline A. Dyck-Jones ◽  
...  
Keyword(s):  
Safety Assessment ◽  
Chart Review ◽  
Hemophilia A ◽  
Retrospective Chart Review ◽  
Severe Hemophilia ◽  
Success Rates ◽  
Plasma Albumin ◽  
Safety And Efficacy ◽  
Antihemophilic Factor ◽  
Partial Success

Abstract Abstract 3670 Introduction: Development of neutralizing antibodies to FVIII is the most serious complication in the management of hemophilia A today. Eradication of the inhibitor with ITI therapy is a common treatment practice however, there are few reports of controlled studies, and much of the current ITI experience is reported from international registries and small site-based case studies. A previous case-series demonstrated successful tolerance in 9/12 (75%) patients using ADVATE [Antihemophilic Factor (Recombinant) Plasma/Albumin Free Method] (rAHF-PFM). Data on the safety and efficacy of rAHF-PFM in ITI therapy have now been formally captured in the recently completed Previously Untreated Patient (PUP-ITI) study, a retrospective chart review (PRE-PAIR), and an ongoing Prospective ADVATE ITI Registry (PAIR). Objectives: To provide a critical assessment of the safety and efficacy of rAHF-PFM in ITI therapy through a review of the cumulative data from PUP-ITI, PRE-PAIR, and PAIR. Methods: PUP study was a prospective, multicenter, open-label, clinical study in PUPs <6 years of age with severe or moderately severe hemophilia (FVIII level ≤2%) who underwent on-demand or prophylactic treatment with rAHF-PFM. Subjects who developed inhibitors against rAHF-PFM could enter the PUP-ITI study and receive ITI. PRE-PAIR was a multicenter, retrospective, chart review of PTPs of any age and any severity of hemophilia A with history of ITI with rAHF-PFM. PAIR is an ongoing non-interventional safety surveillance registry of subjects prescribed rAHF-PFM for ITI. In all three studies, the choice of ITI regimen was at the discretion of the investigator; however, for the PUP-ITI study, the ITI regimen was based on site-specific ITI data and/or institutional guidelines, or as described in peer reviewed literature. The primary endpoints for PUP-ITI and PRE-PAIR were the success rate of ITI. The PAIR report was an interim safety assessment that did not examine efficacy endpoints. For PUP-ITI and PRE-PAIR, the definitions of success required the subject to have achieved 2 consecutive negative inhibitor test results and if data available, demonstrated normalized FVIII recovery. For PRE-PAIR, partial success was defined as achieving negative titer but without normalized recovery. Results: In PUP-ITI, a total of 11 subjects initiated ITI; 3 withdrew and 8 completed ITI. In PRE-PAIR, 35 subjects were enrolled, 30 of which were evaluable per protocol. Of these 30 subjects, 20 had moderately severe to severe hemophilia A (FVIII ≤2%), and high-titer (>5 BU) inhibitor. As of Sept 4, 2010, 18 subjects had been enrolled in PAIR and were included in an interim safety assessment. Over all 3 studies, most commonly prescribed initial dose regimen in subjects with high inhibitor titer prior to initiation of ITI was 100 IU/kg QD (17/37 [46%]), followed by 200 IU/kg QD (11/37 [30%]), and any dose at a frequency of <1/day (9/37 [24%]). In the low titer inhibitor subjects the most commonly prescribed regimen were various doses with a frequency of <1/day (13/22 [59%] subjects). Of the 11 subjects in the PUP study who participated in the PUP-ITI study, 3 withdrew and 8 (72.7%) achieved success (95% CI: 43.4%, 90.3%). All 8 subjects (100%) achieved success, with 1st negative titer at a median time of 1.8 months (0.0 - 4.1 months) and the 2nd negative titer at 3.0 months (1.1 – 9.0 months). In PRE-PAIR, sum of complete and partial success rates gave a total success rate of 76.7% (23/30) in subjects who met inclusion criteria (95% CI: 59.1, 88.2%). During these 3 studies, there were no SAEs related to rAHF-PFM ITI therapy and 6 non-serious AEs in 3 subjects considered to be related to rAHF-PFM (diarrhea, vomiting, pain following bleed, mild urticaria, and mild fever). Conclusions: In 2 clinical studies of rAHF-PFM therapy in ITI treatment, rAHF-PFM was found to be efficacious in a variety of dosing regimens reflective of current standards of practice in hemophilia care. Overall success rates ranged from 72.7% in PUP-ITI to 76.7% in PRE-PAIR. Success rates in these 2 rAHF-PFM studies are similar to those reported in published literature. In all 3 ITI studies, there were no product related SAEs and 6 non-serious AEs in 3 subjects considered to be related to rAHF-PFM, suggesting that rAHF-PFM used for ITI has a similar risk profile established in routine clinical use. These data suggest that ITI treatment with rAHF-PFM was both effective and safe. Disclosures: Spotts: Baxter Bioscience: Employment. Off Label Use: ADVATE [Antihemophilic Factor (Recombinant) Plasma/Albumin Free Method] (rAHF-PFM)use in ITI therapy. Abbuehl:Baxter Bioscience: Employment. Luu:Baxter Bioscience: Employment. Song:Baxter Bioscience: Employment. Dyck-Jones:Baxter Bioscience: Employment. Guzman-Becerra:Baxter Bioscience: Employment. Wu:Baxter Bioscience: Employment. Oh:Baxter Bioscience: Employment. Zoerer:Baxter Bioscience: Employment. Sosa:Baxter Bioscience: Employment. Stephens:Baxter Bioscience: Employment. Yamamoto:Baxter Bioscience: Employment. Ewenstein:Baxter Bioscience: Employment.

Sucrose Formulated Recombinant Human Antihemophilic Factor VIII Is Safe and Efficacious for Treatment of Hemophilia A in Home Therapy

2000 ◽  
Vol 83 (06) ◽  
pp. 811-816 ◽  
Author(s):  
E. Gorina ◽  
E. Kellermann ◽  
E. Vosburgh ◽  
T. C. Abshire ◽  
H.-H. Brackmann ◽  
...  
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
De Novo ◽  
Pharmacokinetic Profile ◽  
Full Length ◽  
Home Therapy ◽  
Safety And Efficacy ◽  
Previously Treated Patients ◽  
New Formulation ◽  
Antihemophilic Factor

SummaryTo add an increased level of safety to antihemophilic factor replacement therapy, a full-length, recombinant Factor VIII (rFVIII) product has been developed without human-derived plasma proteins during purification and formulation and using an additional solvent/detergent viral inactivation step. This first clinical trial of a sucrose-formulated full-length rFVIII (rFVIII-FS) was conducted in previously treated patients (≥100 prior exposure days) with severe (<2% FVIII) hemophilia A in North America (NA) and Europe (EU). Pharmacokinetic profiles for rFVIII-FS were compared with those of currently licensed rFVIII product (Kogenate®) in 35 patients. Safety and efficacy during home therapy were evaluated in 71 patients. The new formulation displayed a pharmacokinetic profile similar to that of rFVIII. Patients on home therapy received a cumulative total of 11,867 exposure days, 12,546 infusions, and 22,443,694 IU of rFVIII-FS. Of 2585 bleeds, 93.5% were treated with 1-2 infusions and 80.5% of responses were rated as excellent or good. No evidence of de novo inhibitor formation was observed. Only 0.27% of infusions were associated with any drugrelated adverse event. Except for an episode of intermittent chest pain with palpitations which ceased after treatment with analgesics, associated adverse events were mild or moderate. Overall, rFVIII-FS provided excellent hemostatic control, was well-tolerated, and caused no significant adverse effects, thus demonstrating safety and efficacy for treatment of bleeds in patients with hemophilia A.

scholarly journals Immunologic Studies of Antihemophilic Factor (AHF, Factor VIII) II. Properties of Cross-reacting Material

Blood ◽  
1970 ◽  
Vol 35 (6) ◽  
pp. 809-820 ◽  
Author(s):  
LEON W. HOYER ◽  
ROBERT T. BRECKENRIDGE
Keyword(s):  
Calcium Phosphate ◽  
Physical Properties ◽  
Factor Viii ◽  
Barium Sulfate ◽  
Genetic Variant ◽  
Hemophilia A ◽  
Procoagulant Activity ◽  
Normal Plasma ◽  
Fraction I ◽  
Antihemophilic Factor

Abstract Patients with a genetic variant of hemophilia A have in their plasmas material which has antigenic characteristics similar to those of antihemophilic factor (AHF). The physical properties of the biologically inactive cross-reacting material (CRM) are like those of AHF from normal plasma. The CRM is concentrated in Cohn fraction I and in cryoprecipitates and is not adsorbed from plasma by calcium phosphate or barium sulfate. It is inactivated by heating to 56° for 30 minutes. The CRM is less sensitive to thrombin inactivation than AHF and is recovered in serum. The similar properties of AHF and CRM support the hypothesis that patients with this genetic variant of hemophilia A synthesize a material similar to AHF but lacking procoagulant activity.

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