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.

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% 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.

Indirect Treatment Comparison of Damoctocog Alfa Pegol versus Turoctocog Alfa Pegol as Prophylactic Treatment in Patients with Hemophilia A.

PURPOSE: To assess the efficacy and FVIII consumption of BAY 94-9027 versus N8-GP in prophylaxis in adolescent and adult patients with severe hemophilia A (HA). PATIENTS AND METHODS: A systematic literature review was conducted to identify studies on the efficacy of BAY-94-9027 and N8-GP for prophylaxis in patients with HA aged ≥12 years without a history of inhibitors. Eight studies met systematic literature review inclusion criteria, but only data from PROTECT VIII on BAY 94-9027 and PATHFINDER 2 on N8-GP could be used for an indirect comparison. Matching-adjusted indirect comparison (MAIC) and simulated treatment comparison were performed. RESULTS: No significant differences (unadjusted and adjusted) were observed in the mean annualized bleeding rate (ABR) for any bleed and proportion of patients with zero bleeds when comparing BAY 94-9027 to N8-GP. The adjusted treatment difference [incidence rate ratio (IRR)] in terms of ABR was 1.11 (95% CI, 0.85-1.44). The odds ratio (OR) of any bleed, measuring the relative effect of BAY 94-9027 versus N8-GP on the proportion of patients with zero bleeds, was 1.03 (95% CI, 0.60-1.77). FVIII consumption was significantly lower in BAY 94-9027 [mean adjusted difference=-1292.57 IU/kg/year (95% CI, ‒2152.44 to ‒432.70)]; a 26.7% reduction in consumption of BAY-94-9027. The results of the sensitivity analyses were similar to the main analysis for mean ABRs, percentages of patients with zero bleeds, and significant reduction in rFVIII consumption. For patients on BAY 94-9027 every-5-days and every-7-days, no differences versus every-4-days N8-GP were observed for the mean ABR for any bleed [IRR=0.90 (95% CI, 0.68‒1.20)] and proportion of patients with zero bleeds [OR=1.06 (95% CI, 0.56‒2.02)]. CONCLUSION: BAY 94-9027 prophylaxis demonstrated 26.7% lower annual consumption when compared to N8-GP with similar efficacy in terms of ABR and percentage of patients with zero bleeds.

Matching-adjusted indirect comparisons of annualized bleeding rate and utilization of BAY 94-9027 versus three recombinant factor VIII agents for prophylaxis in patients with severe hemophilia A.

Background: BAY 94-9027 is an extended half-life recombinant factor VIII (rFVIII) that prevents bleeding in persons with hemophilia A at twice-weekly, 5-day, and 7-day dosing intervals. In rare diseases such as hemophilia, where small populations preclude head-to-head comparisons in randomized controlled trials, outcomes from different studies can be compared by matching-adjusted indirect treatment comparisons (MAICs) via matched summary statistics of individual patient data. This study compared MAIC-adjusted outcomes of BAY 94-9027 with other FVIII agents for prophylaxis of hemophilia. Methods: Weighted patient data from the BAY 94-9027 PROTECT VIII trial were used to compare annualized bleeding rates (ABRs), percentage of patients with zero bleeds, and factor utilization against published data on rFVIII-Fc fusion protein (rFVIIIFc), BAX 855, and recombinant antihemophilic factor/plasma/albumin-free method (rAHF-PFM). Results: After matching BAY 94-9027 and comparators, the mean BAY 94-9027 utilization was significantly lower than rFVIIIFc pre- and post-matching (66.2 vs 82.2 IU/kg/week; 66.5 vs 82.2 IU/kg/week; both P<0.001). Median BAY 94-9027 utilization (IU/kg/week) trended lower than BAX 855 (64.3 vs 87.4) and rAHF-PFM (2004 study: 64.0 vs 107.5; 2012 study: 63.6 vs 109.9). Mean ABRs and percentages of patients with zero bleeds were similar post-matching between BAY 94-9027 and comparators. Conclusion: BAY 94-9027 demonstrated similar MAIC-adjusted ABR with lower utilization than rFVIIIFc, BAX 855, and rAHF-PFM.

Exploring the Impact of Infusion Frequency in Hemophilia A: Exit Interviews with Patients Participating in BAY 94-9027 Extension Studies (PROTECT VIII).

INTRODUCTION: Prophylactic treatment of severe hemophilia A is burdensome, requiring frequent intravenous injections. Extended half-life (EHL) factor VIII replacement therapies offer longer intervals between infusions while still meeting efficacy and safety outcomes; however, patient perspectives following long-term use of such products in the real-world remain unknown. OBJECTIVE: We aimed to explore the importance of infusion frequency and the potential benefits of reduced infusion frequency among patients receiving prophylactic treatment with an EHL product (BAY 94-9027). METHODS: Patients with severe hemophilia A participating in the PROTECT VIII extension study were invited to participate in a semi-structured, concept elicitation 'exit' interview to discuss their experiences. Participants were recruited from Israel, The Netherlands, and the US. Interview transcripts were translated into English and analyzed using thematic analysis methods. RESULTS: Sixteen participants (29-68 years of age) infusing with BAY 94-9027 once every 7 days, once every 5 days, or twice weekly were interviewed. Participants reported infusion frequency (alongside efficacy) as the most important treatment attribute influencing their satisfaction with therapy. Patient-reported benefits of reduced infusion frequency and longer duration of factor coverage included greater ability to participate in physical activities; better vein health; less time to schedule and administer factor VIII; reduced impact on work; and improved emotional well-being. CONCLUSIONS: This study provides rich insights into the experiences of patients with EHL products and the value of reduced infusion frequency. Such data could be of value to a range of stakeholders (e.g. regulators, payers) and facilitate patient-clinician discussions to promote tailored treatment decisions.