scholarly journals BUDGET IMPACT OF AN EXTENDED HALF LIFE RECOMBINANT FVIII THERAPY FOR A HYPOTHETICAL POPULATION OF SEVERE HEMOPHILIA A PATIENTS IN AN INSURED POPULATION IN THE UNITED STATES

2016 ◽  
Vol 19 (3) ◽  
pp. A243
Author(s):  
M. Bron ◽  
Y. Xiong ◽  
J. Booth ◽  
P.H. Glover ◽  
J. Epstein
Keyword(s):  
United States ◽  
Half Life ◽  
Budget Impact ◽  
Hemophilia A ◽  
The United States ◽  
Severe Hemophilia ◽  
Recombinant Fviii

scholarly journals Budget Impact Analysis of Prolonged Half-Life Recombinant FVIII Therapy for Hemophilia in the United States

2017 ◽  
Vol 20 (1) ◽  
pp. 93-99 ◽  
Author(s):  
Suzanne McMullen ◽  
Brieana Buckley ◽  
Eric Hall ◽  
Jon Kendter ◽  
Karissa Johnston
Keyword(s):  
United States ◽  
Half Life ◽  
Impact Analysis ◽  
Budget Impact ◽  
The United States ◽  
Budget Impact Analysis ◽  
Recombinant Fviii

scholarly journals Adoption of Prophylaxis in the United States in the Era of Extended Half-Life Factor Concentrates

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2467-2467
Author(s):  
Lynn M. Malec ◽  
Gilbert C. White ◽  
Stacy E. Croteau ◽  
Dunlei Cheng ◽  
Margaret V. Ragni
Keyword(s):  
United States ◽  
Board Of Directors ◽  
Half Life ◽  
Research Funding ◽  
Hemophilia A ◽  
The United States ◽  
Hemophilia B ◽  
Severe Hemophilia ◽  
Advisory Committees ◽  
Number Of Patients

Abstract Background: Use of prophylaxis is the evidence-based strategy to prevent joint bleeds and reduce arthropathy for patients with severe hemophilia however, prophylaxis has not been universally adopted in the United States. Amongst patients with severe hemophilia enrolled in the ATHNdataset, the largest database of patients with disorders of hemostasis and thrombosis in the United States, as of 2015, 37% of patients with hemophilia A, and 45% of patients with hemophilia B do not receive prophylaxis. With the approval of extended half-life (EHL) factor products, patients and providers have options for less treatment-intense and burdensome prophylaxis. With the changing landscape of available hemophilia products, we aimed to quantify the number of patients treated at U.S. HTCs on prophylaxis utilizing the ATHNdataset with the objective determining the impact of EHL products on the proportion of patients with severe hemophilia receiving prophylaxis and to characterize use of prophylaxis according to age, race and ethnicity, geographic region, and payer. Methods: The ATHNdataset, a HIPAA compliant limited dataset sponsored by the American Thrombosis and Hemostasis Network (ATHN), was accessed as of June 30, 2018. The proportion of subjects with severe hemophilia on prophylaxis were compared to those on demand by age cohort. The proportion of subjects on prophylaxis was analyzed by race, ethnicity, insurance status, and hemophilia treatment center region. For each group receiving prophylaxis, the product (EHL versus standard half-life (SHL)), dose and frequency of treatment was analyzed. Results: ATHNdataset included 6,160 severe hemophilia patients using factor replacements, 5,234 individuals with hemophilia A and 926 individuals with hemophilia B. Overall, 76.0% (n=4,864) of patients with severe hemophilia are on prophylaxis whereas 24.0% (n=1426) are on demand; this included a total of 76.6% of patients with severe hemophilia A and 72.9% of patients with severe hemophilia B on prophylaxis. Treatment type (prophylaxis or not) had significant associations with age (p-value <0.001), ethnicity (p<0.001), race (p=0.005), hemophilia treatment center (HTC) region (p<0.001), and hemophilia type (p=0.015) (Table 1). Prophylaxis was not significantly correlated with payer (p=0.847) with a similar number of patients with Medicare/Medicaid or private insurance receiving prophylaxis. Among patients on prophylaxis, 30.8% (n=1,462) are prescribed EHL products including 27.4% of patients with hemophilia A and 50.4% with hemophilia B. In terms of dosing frequency (n=758), 73.8% of hemophilia A patients on prophylaxis receive EHL two times per week while 73.7% (n=1,906) receive SHL every other day (Table 2). Of hemophilia B patients using EHL products, 63.3% of patients receive prophylaxis once weekly, 12.7% every 10 days, and 15.0% every 2 weeks (Table 2). Discussion: The ATHNdataset highlights increased use of prophylaxis over the past 3 years in the U.S. with 76.6% of patients with severe hemophilia A and 72.9% of patients with severe hemophilia B currently receiving prophylactic therapy as compared to 63% and 55% of patients, respectively, in 2015. Further, the majority (83.7%) of patients are beginning prophylaxis according to the World Federation of Haemophilia recommendation to initiate prophylaxis by three years of age. There has been an uptake of the use of EHL factor products including a majority of patients (50.4%) with severe hemophilia B. Although not captured in the ATHNdataset, a plausible reason for the increased uptake of EHL in the hemophilia B population includes the data that 91% of patients are able to dose between weekly or less frequently. As the hemophilia treatment landscape continues to evolve, it is important to continue to understand the adoption of these new products into practice and to examine their real-world impact. Disclosures Malec: Shire: Consultancy; Bioverativ: Consultancy; Bayer: Consultancy; Bioverativ: Research Funding. White:Biomarin: Other: DSMB; Bioverativ: Other: DSMB; Bayer: Other: GRAC; Shire: Other: Physician Leadership Group; Novo Nordisk: Consultancy; Asklepios: Other: Scientific Advisory Board; Invitrox: Other: Scientific Advisory Board; Pfizer: Equity Ownership. Croteau:Biomarin: Consultancy; Bioveritiv: Consultancy; Catalyst Biosciences: Consultancy; CSL-Behring: Consultancy; Genetech: Consultancy, Research Funding; Novo Nordisk: Consultancy; Octapharma: Consultancy, Honoraria, Research Funding; Pfizer: Research Funding; Spark Therapeutics: Research Funding; Tremeau Pharmaceuticals: Consultancy; Bayer: Consultancy; Baxalta/Shire: Consultancy, Research Funding. Ragni:Sangamo: Research Funding; CSL Behring: Research Funding; Bioverativ: Consultancy, Research Funding; SPARK: Consultancy, Research Funding; Alnylam: Membership on an entity's Board of Directors or advisory committees, Research Funding; Biomarin: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Research Funding; Shire: Research Funding; MOGAM: Membership on an entity's Board of Directors or advisory committees.

Common Genetic Variants in ABO and CLEC4M Modulate the Pharmacokinetics of Recombinant FVIII in Severe Hemophilia A Patients

2020 ◽  
Vol 120 (10) ◽  
pp. 1395-1406 ◽  
Author(s):  
Iris Garcia-Martínez ◽  
Nina Borràs ◽  
Marta Martorell ◽  
Rafael Parra ◽  
Carme Altisent ◽  
...  
Keyword(s):  
Blood Group ◽  
Half Life ◽  
Robust Regression ◽  
Hemophilia A ◽  
Illumina Miseq ◽  
Activity Levels ◽  
Severe Hemophilia ◽  
Single Nucleotide Variants ◽  
Common Genetic Variants ◽  
Recombinant Fviii

AbstractThe pharmacokinetic (PK) response of severe hemophilia A (HA) patients to infused factor VIII (FVIII) shows substantial variability. Several environmental and genetic factors are associated with changes in FVIII plasma levels and infused FVIII PK. Based on the hypothesis that factors influencing endogenous FVIII can affect FVIII PK, the contribution of single-nucleotide variants (SNVs) in candidate genes was investigated in 51 severe HA patients. The effects of blood group, F8 variant type, von Willebrand factor antigen and activity levels, age, and weight were also explored. The myPKFiT device was used to estimate individual PK parameters, and SNVs and clinically reportable F8 variants were simultaneously analyzed in an Illumina MiSeq instrument, using the microfluidics-based Fluidigm Access Array system. The contribution of SNVs to FVIII half-life and clearance was addressed by robust regression modeling, taking into account other modulators. In line with previous studies, we provide robust evidence that age, body weight, and blood group, as well as SNVs in ABO and CLEC4M, participate in the variability of FVIII PK in HA patients. Main results: each copy of the rs7853989 (ABO) allele increases FVIII half-life by 1.4 hours (p = 0.0131) and decreases clearance by 0.5 mL/h/kg (p = 5.57E-03), whereas each additional rs868875 (CLEC4M) allele reduces FVIII half-life by 1.1 hours (p = 2.90E-05) and increases clearance by 0.3 mL/h/kg (p = 1.01E-03). These results contribute to advancing efforts to improve FVIII replacement therapies by adjusting to each patient's PK profile based on pharmacogenomic data. This personalized medicine will decrease the burden of treatment and maximize the benefits obtained.

scholarly journals All-Cause and Inhibitor-Related Mortality in Non-Severe Hemophilia Α Patients in the United States

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 902-902 ◽  
Author(s):  
Ming Y. Lim ◽  
Dunlei Cheng ◽  
Christine L. Kempton ◽  
Nigel S. Key
Keyword(s):  
United States ◽  
At Risk ◽  
Mortality Rate ◽  
Hemophilia A ◽  
The United States ◽  
Severe Hemophilia ◽  
All Cause Mortality ◽  
Related Mortality ◽  
Observation Period

Introduction: The majority of published studies evaluating inhibitors have focused mainly on patients with severe hemophilia A. In non-severe hemophilia A (NSHA) patients, the development of inhibitors can have a profound clinical impact, with major bleeding complications similar to that of patients with severe or acquired hemophilia. Yet, epidemiological data on inhibitors in NSHA patients, specifically mortality, is scarce and currently limited to the European and Australian cohort [Eckhardt CL, et al. J Thromb Haemost. 2015 Jul;13(7):1217-251]. Objectives: To determine the all-cause and inhibitor-related mortality in NSHA patients in the United States using the ATHNdataset Methods: Subjects and study design The ATHNdataset is a 'limited dataset' as defined under the United States Health Insurance Portability and Accountability Act (HIPAA) to be free of protected health information, with data collection by more than 130 hemophilia treatment centers (HTC) across the United States. It includes patients with congenital bleeding disorders in the United States who have authorized the sharing of their demographic and clinical information for research. Data collection and definitions The ATHNdataset was queried on December 31, 2018 to extract the following information on NSHA patients: Patient demographics, inhibitor status, date of death, and primary cause of death. The presence of inhibitors was defined as: (i) ≥ 2 positive Bethesda inhibitor assay titers of ≥ 1.0 BU/mL; or (ii) a decrease in plasma FVIII coagulant activity (FVIII:C) to at least 50% of baseline activity and/or spontaneous bleeding symptoms in patients with inhibitor titers between 0.6 and 1.0 BU/mL. Patients who had a negative inhibitor history or have never been tested for FVIII inhibitors were classified as negative for inhibitors. Statistical analyses The person-year mortality rate was calculated as the ratio of the number of deaths to the number of person-years at risk, presented as rates per 1000 person-years. Person-years at risk was calculated for each patient as the time between the start of the observation period (January 1, 2010 or date of birth for patients who are born later) and the end of the observation period (date of death, loss-to follow-up or December 31, 2018). Patients who were deceased or lost to follow-up before January 1, 2010 were not included in the analysis. Inhibitor person-years at risk for inhibitor patients was calculated from January 1, 2010 if the first positive inhibitor test occurred prior to January 1, 2010 or from the date of the first positive inhibitor test that occurred during the observation period until the end of the observation period. Inhibitor-related death was attributed to all patients who had a positive inhibitor history. Mortality rates were compared between inhibitor and non-inhibitor patients using z- test. Results: Between 1/1/2010 and 12/31/2018, the ATHNdataset included 6,606 NSHA patients who were born between 1920 and 2018. Patients were observed for a total of 56,064 person-years. 85.57% (n = 5,653) of these patients were observed for the full nine years. The average follow-up time per patient was almost 8.5 years. Inhibitors developed in 171 (2.59%) NSHA patients. The median age for inhibitor development was 13 years (IQR, 6 - 37 years) and the mean age was 22 years. Demographics characteristics of the patients are listed in Table 1. All-cause mortality At the end of follow-up, there was a total of 136 deaths in the NSHA population, occurring at a median age of 63 years (IQR, 51 - 75 years). The overall all-cause mortality rate was 2.43 per 1,000 person-years (95% CI: 2.02 - 2.83). The most common primary cause of death was cancer (n=27, 19.9%) (Table 2). Inhibitor-related mortality Three deaths were associated with inhibitors. Inhibitor-related mortality rate was 2.40 per 1,000 person-years, whereas among the never inhibitor group, the mortality rate was 2.44 per 1,000 person-years (p = 0.790). Mortality risk ratio between inhibitor and never inhibitor was 0.98 (95% CI: 0.31 - 3.08). Conclusion: In NSHA patients, the development of inhibitors occurred at a relatively early age and was not associated with increased mortality. Disclosures Kempton: Novo Nordisk: Research Funding; Octapharma: Honoraria; Genentech: Honoraria; Spark Therapeutics: Honoraria. Key:Uniqure BV: Research Funding.

scholarly journals Management of inhibitors in persons with non‐severe hemophilia A in the United States

2020 ◽  
Vol 96 (1) ◽  
Author(s):  
Ming Y. Lim ◽  
Dunlei Cheng ◽  
Michael Recht ◽  
Christine L. Kempton ◽  
Nigel S. Key
Keyword(s):  
United States ◽  
Hemophilia A ◽  
The United States ◽  
Severe Hemophilia

scholarly journals Direct comparison of two extended-half-life recombinant FVIII products: a randomized, crossover pharmacokinetic study in patients with severe hemophilia A

2019 ◽  
Vol 98 (9) ◽  
pp. 2035-2044 ◽  
Author(s):  
Anita Shah ◽  
Alexander Solms ◽  
Sara Wiegmann ◽  
Maurice Ahsman ◽  
Erik Berntorp ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Half Life ◽  
Hemophilia A ◽  
Severe Hemophilia ◽  
Recombinant Fviii

Real-World Age-Stratified FVIII Consumption and Bleed Outcomes Before and After Switching to Rurioctocog Alfa Pegol in a Retrospective, Observational Study Using US Specialty Pharmacy Data

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2411-2411
Author(s):  
Maureen Watt ◽  
Scott Milligan
Keyword(s):  
Clinical Trial ◽  
Real World ◽  
Half Life ◽  
Research Funding ◽  
Hemophilia A ◽  
The United States ◽  
Patient Data ◽  
Severe Hemophilia ◽  
Before And After ◽  
Pharmacy Data

Introduction: The safety and efficacy of rurioctocog alfa pegol (BAX 855, SHP-660, TAK-660; Adynovate®; Baxalta US Inc., a Takeda company, Lexington, MA, USA) in patients with severe hemophilia A has been reported previously (Konkle BA et al., Blood 2015, 126:1078-85; Brand B et al., Haemophilia 2016, 22:e251-8; Mullins ES et al., Haemophilia 2017, 23:238-46); however, research describing patient experience with extended half-life (EHL) recombinant factor VIII (FVIII) products outside clinical trials is limited. The objective of this study was to assess real-world utilization of TAK-660 in patients with hemophilia A and describe their clinical profiles before and after switching to TAK-660. Factor consumption and bleed outcomes stratified by age (<18 and ≥18 years) are reported herein. Methods: This was a retrospective, observational database study of patient data from US specialty pharmacies. Pharmacy data sources included patient records, prescriptions, and patient-reported bleed logs. Informed consent was obtained for all analyzed patient data. Eligible patients with hemophilia A were treated with prophylactic TAK-660 with on-label dosing from November 2015 to September 2018, and had received ≥90 days of FVIII (standard half-life [SHL] or EHL) therapy before switching to TAK-660. Main exclusion criteria were participation in a TAK-660 clinical trial before/during this study, only on-demand treatment before switching to TAK-660, or presence of active FVIII inhibitor requiring treatment and/or use of immune tolerance induction during the study period. Assessments included prior hemophilia therapy, FVIII administration frequency and consumption, and annualized bleeding rate (ABR) before and after switching to TAK-660. Results: Data was collected from 82 patients (of 61 providers in 44 practices across 25 states in the United States): 44% of the patients (36/82) were <18 years old; 56% (46/82) were ≥18 years old (none were ≥60 years old); 83% (68/82) had severe hemophilia A; and 88% (72/82) had received prior SHL-FVIII treatment. The SHL antihemophilic factor (recombinant) (Advate®; Baxalta US Inc., a Takeda company, Lexington, MA, USA) was used by 67% (55/82) of patients overall, of whom 47% (26/55) were <18 years old and 53% (29/55) were ≥18 years old. Compared with any prior FVIII therapy, switching to TAK-660 increased FVIII dose per administration in patients <18 and ≥18 years old (+39.5% and +22.9%, respectively), while their weekly administration frequency decreased (-21.4% and -28.1%, respectively; Table 1). Weekly FVIII consumption increased in patients aged <18 years (+11.2%) and decreased in those aged ≥18 years (-12.8%). FVIII administration frequency and consumption by prior SHL- or EHL-FVIII are reported in Table 1. ABR data before and after switching were available in 47 of 82 patients. Compared with any prior FVIII therapy, mean ABR decreased in patients aged <18 years (-39.5%; 2.8 to 1.7) and ≥18 years (-50.3%; 3.4 to 1.7) with TAK-660 treatment (Table 2). Changes in mean ABR by prior FVIII therapy and disease severity are reported in Table 2. The small number of patients who received prior EHL FVIII was a limiting factor in the comparison of patients who received prior SHL- and EHL-FVIII therapy. Conclusions: In patients with hemophilia A previously treated with SHL- or EHL-FVIII products, switching to TAK-660 prophylaxis resulted in a significant decrease in ABR of 40-50% in both age groups analyzed. The adult population (ie, ≥18 years old) showed a tendency for reduced weekly FVIII consumption. These findings from real-world data are in agreement with TAK-660 clinical trial results. The observed differences in FVIII consumption between patients <18 and ≥18 years old may have been in part a result of age-related changes in bleeding patters, growth, and other factors. Disclosures Watt: Shire International GmbH, a Takeda company: Employment, Other: a Takeda stock owner. Milligan:Sanofi: Research Funding; Merck: Research Funding; Gilead: Research Funding; Amgen: Research Funding; AbbVie: Research Funding; Trio Health: Employment; Viiv: Research Funding.

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