title: A Budget Impact Model of Hemophilia Bypassing Agent Prophylaxis Relative to Recombinant Factor VIIa On-Demand.
abstract: BACKGROUND
  Hemophilia patients use factor-clotting concentrates (factor VIII for hemophilia A and factor IX for hemophilia B) for improved blood clotting. These products are used to prevent or stop bleeding episodes. However, some hemophilia patients develop inhibitors (i.e., the patient's immune system develops antibodies against these factor concentrates). Hence, these patients do not respond well to the factor concentrates. A majority of hemophilia patients with inhibitors are managed on-demand with the following bypassing agents: recombinant factor VIIa (rFVIIa) and activated prothrombin complex concentrate (aPCC). The recently published U.S. registries Dosing Observational Study in Hemophilia (DOSE) and Hemostasis and Thrombosis Research Society (HTRS) reported higher rFVIIa on-demand use for bleed management than previously described.
  
  
  OBJECTIVE
  To estimate aPCC and rFVIIa prophylaxis costs relative to rFVIIa on-demand treatment cost based on rFVIIa doses reported in U.S. registries.
  
  
  METHODS
  A literature-based cost model was developed assuming a base case on-demand annual bleed rate (ABR) of 28.7 per inhibitor patient, which was taken from a randomized phase 3 clinical trial. The doses for rFVIIa on-demand were taken from the median dose per bleed reported by the DOSE and HTRS registries. Model inputs for aPCC and rFVIIa prophylaxis (i.e., dosing and efficacy) were derived from respective randomized clinical trials. Cost analysis was from the U.S. payer perspective, and only direct drug costs were considered. The drug cost was based on the Medicare Part B 2014 average sale price (ASP). Two-way sensitivity and threshold analyses were performed by simultaneously varying on-demand ABR, prophylaxis efficacy, and unit drug cost. In addition to studying relative costs associated with on-demand and prophylaxis treatments, relative cost per bleeding episode avoided were also calculated for aPCC and rFVIIa prophylaxis treatments. The prophylaxis efficacy reported in the trials were used to determine the number of bleeding episodes avoided.
  
  
  RESULTS
  Based on the median on-demand dose of 695 mcg per kg per bleed, reported by the DOSE registry, the annual rFVIIa on-demand cost was $34,009 per kg of body weight. The annual rFVIIa on-demand cost was $22,020 per kg of body weight when the median dose of 450 mcg per kg per bleed reported by the HTRS registry was considered. The annual cost rose to $38,461 per kg of body weight when the rFVIIa on-demand dose of 786 mcg per kg per bleed among patients infusing an initial dose ≥ 250 mcg per kg was considered. The aPCC (85 units per kg per every other day) and rFVIIa (90 mcg per kg per every day) annual prophylaxis costs were $26,536 and $60,700, respectively. Also, aPCC and rFVIIa prophyaxis treatments were estimated to prevent a total of 20.8 and 12.9 annual bleeding episodes, respectively. When compared with the on-demand dose of 695 mcg per kg per bleed (DOSE registry), the annual aPCC and rFVIIa prophylaxis costs were 21.9% lower and 78.4% higher, respectively. Additionally, aPCC prophylaxis saved $360 per kg for each bleeding episode avoided. rFVIIa prophylaxis cost $2,066 per kg for each bleeding episode avoided. Compared with the on-demand dose of 450 mcg per kg per bleed (HTRS registry), aPCC and rFVIIa prophylaxis costs were 20.5% and 174.9% higher, respectively. In this case, aPCC and rFVIIa prophylaxis treatment costs were $217 per kg and $2,995 per kg, respectively, for each bleeding episode avoided. aPCC and rFVIIa prophylaxis costs were 31.0% lower and 57.8% higher, respectively, when compared with the rFVIIa on-demand dose of 786 mcg per kg per bleed, among patients infusing an initial dose ≥ 250 mcg per kg (HTRS registry). In this case, aPCC prophylaxis saved $573 per kg for each bleeding episode avoided, while rFVIIa prophylaxis costs $1,724 per kg for each bleeding episode avoided. Results of the 2-way sensitivity analyses were robust in the majority of the scenarios considered.
  
  
  CONCLUSIONS
  aPCC prophylaxis may be cost saving for managing hemophilia patients with inhibitors who bleed frequently and infuse significant quantities of rFVIIa on-demand.
authors.affiliation: 1 PhD Student, Pharmaceutical Economics and Policy, University of Southern California, Los Angeles.
authors.forename: Darshan A
authors.initials: DA
authors.lastname: Mehta
authors.affiliation: 2 Senior Manager, Baxalta US, Cambridge, Massachusetts.
authors.forename: Abiola O
authors.initials: AO
authors.lastname: Oladapo
authors.affiliation: 3 Director, Baxalta US, Westlake Village, California.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Epstein
authors.affiliation: 4 Senior Manager, Global Medical Affairs, Baxalta US, Deerfield, lllinois.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Novack
authors.affiliation: 5 Egan Family Foundation Chair in Transitional Medicine, Division of Hematology/Oncology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Ellis J
authors.initials: EJ
authors.lastname: Neufeld
authors.affiliation: 6 Professor, Pharmaceutical Economics and Policy, and Professor, Health Policy and Economics, University of Southern California, Los Angeles.
authors.forename: Joel W
authors.initials: JW
authors.lastname: Hay
mesh_terms: D001779:Blood Coagulation Factors / Q000191:economics* / Q000627:therapeutic use; D002017:Budgets; D017326:Clinical Trials, Phase III as Topic; D003362:Cost-Benefit Analysis / Q000191:economics; D016527:Drug Costs; D015942:Factor VIIa / Q000191:economics* / Q000627:therapeutic use; D017048:Health Care Costs; D006467:Hemophilia A / Q000188:drug therapy / Q000191:economics*; D002836:Hemophilia B / Q000188:drug therapy / Q000191:economics*; D006470:Hemorrhage / Q000188:drug therapy / Q000191:economics; D006801:Humans; D008297:Male; D016345:Medicare Part B; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000191:economics / Q000627:therapeutic use; D012042:Registries; D014481:United States
chemical_list: D001779:Blood Coagulation Factors; D011994:Recombinant Proteins; C025667:prothrombin complex concentrates; C103587:recombinant FVIIa; D015942:Factor VIIa