von Willebrand factor (VWF) concentrates may be required for on-demand treatment (ODT) or long-term prophylaxis (LTP) in von Willebrand disease (VWD). This study assesses the cost-effectiveness of LTP compared with ODT in VWD patients treated with Voncento in the United Kingdom (UK). A Markov structure was developed to estimate quality-adjusted life years (QALYs) and costs of VWD treatment over a lifetime horizon. Treatment options included ODT or LTP. For both options, we assumed plasma-derived VWF/factor VIII (pdVWF/FVIII) 2.4:1 (Voncento) as the VWF product used. Clinical parameters were obtained from published literature and Voncento's summary characteristics. Utility weights were obtained from published literature. Costs (in 2021 GBP) and outcomes were discounted annually by 3.5%. Sensitivity analyses were conducted. Three baseline annual bleed rate (ABR) scenarios (11, 26.5 and 39.6) were considered. In the base-case analyses, Voncento LTP resulted in lower costs (-£831,206) and greater QALY (6.14) versus ODT. Savings were primarily due to reductions in product use required (-£529,571) and bleed-related other medical costs (-£301,352). Compared with ODT, LTP also resulted in 322.52 fewer major bleeds and 515.68 fewer minor bleeds over a lifetime horizon. Probabilistic sensitivity analyses showed dominance in 96.12% of simulations and cost-effectiveness in 97.68% of simulations. For the 39.6 ABR scenario, LTP was also dominant compared with ODT. Results suggest that Voncento LTP is more effective and cost-saving compared with ODT in the UK for VWD patients with higher ABR. Prophylaxis for patients with frequent bleeds is likely to be a cost-saving and effective strategy.

OBJECTIVE:von Willebrand Disease (vWD) is the most common congenital bleeding disorder, with an estimated prevalence in Spain of 0.01%. The aim was to assess the cost-utility of Haemate-P compared with present alternatives in the treatment of vWD in Spain. METHODS:A Markov model was developed in Microsoft Excel to estimate the cost-effectiveness of various treatments for vWD over a lifetime horizon. Transition probabilities among health states were based on age and number of bleeding events. Treatment strategies compared included Haemate-P, Fanhdi, and Wilate in long-term prophylaxis (LTP) or on-demand treatment (ODT). Costs and quality-of-life were measured based on patient age, treatment, and number of bleeding events incurred. Both costs and utilities were discounted at 3%. One-way and probabilistic sensitivity analyses were performed. RESULTS:When comparing LTP regimens, Haemate-P was less costly and numerically more effective than both Fanhdi (incremental costs = -€1,313,845; incremental quality-adjusted life-years [QALY] = 0.13) and Wilate (incremental costs = -€2,233,940; incremental QALY = 0.29). For ODT, Haemate-P was assumed to have equal effectiveness as Fanhdi and Wilate but reduced the costs by €696,857 and €1,145,780, respectively. Haemate-P prophylaxis was more effective and less costly compared with Haemate-P on-demand in the base case (incremental costs = -€633,317; incremental QALY = 0.90). Results were generally robust to sensitivity analyses. CONCLUSIONS:In patients with severe vWD experiencing a high bleed rate, Haemate-P prophylaxis is a less costly and potentially more effective treatment strategy and Haemate-P is cost-saving among on-demand strategies.

INTRODUCTION:Consensus over the definition of recombinant factor VIII (rFVIII) product classification in haemophilia A is lacking. rFVIII products are often classified as standard half-life (SHL) or extended half-life (EHL); despite this, no universally accepted definition currently exists. One proposed definition includes half-life, area under the curve, and technology designed to extend half-life; however, the International Society on Thrombosis and Haemostasis defines activity over time as the most intuitive information for building treatment regimens and the World Federation of Hemophilia describes rFVIII product classification in terms of infusion frequency.AIM:To summarise published data on the clinical and pharmacokinetic criteria used to define rFVIII product classification.METHODS:PubMed and EMBASE database searches of English-language articles (2002-2022) were conducted using search strings to identify the relevant population, intervention, and outcomes (e.g., clinical and pharmacokinetic parameters). Articles then underwent title/abstract and full-text screens.RESULTS:Among 1147 identified articles, 62 were included. Half-life was the most widely reported outcome with no clear trends or product groupings observed. No clear groupings emerged among other outcomes, including infusion frequency, consumption, and efficacy. As activity over time was reported in few articles, further investigation of its relevance to rFVIII product classification is warranted.CONCLUSION:The findings of this systematic literature review suggest that parameters other than half-life might be important for the development of a comprehensive and clinically relevant rFVIII product classification definition. There seems to be an opportunity to consider parameters that are clinically meaningful and useful for shared decision-making in haemophilia A treatment.

An important aspect of improving care for people with hemophilia B (HB) is developing optimal treatment strategies. Here we aimed to provide in-silico evidence, comparing the estimated optimal posology of factor IX (FIX) products to support the patient-physician decision-making process. A population pharmacokinetic (popPK) model-based assessment comparing the performance of FIX products (rFIX, rIX-FP, rFIXFc, N9-GP) was developed. PopPK analyses were used to determine a product’s optimal posology to target predefined steady-state FIX activity trough levels in a hypothetical population of 10,000 people with severe HB. Model-derived optimal posologies were compared across several parameters including trough levels, proportion of patients per regimen and consumption, considering 64 hypothetical patient scenarios of different FIX trough level targets and ages. Results indicated a marked difference between FIX products estimated to achieve target trough levels, consumption and dosing frequencies. rIX-FP was associated with higher trough levels than rFIX and rFIXFc, at a lower weekly dose and administration frequency, across all age groups. N9-GP use in adolescents and adults was associated with lower consumption compared with rIX-FP. Insights from this study may be utilized by clinicians to inform decision-making, by considering the model-generated estimated optimal posologies alongside multiple clinical factors and patient preferences.

Prophylactic treatment of hemophilia B with recombinant factor IX (rFIX) molecules with enhanced pharmacokinetics including rIX-FP (albutrepenonacog alfa; Idelvion©) and rFIXFc (eftrenonacog alfa; Alprolix©) have commonly been used in the clinic. In the absence of head-to-head comparative trials, the aim of this study was to estimate the efficacy of rIX-FP versus rFIXFc using matching-adjusted indirect comparisons (MAICs). MAIC analyses leveraged individual patient data from the PROLONG-9FP trial and published summary-level data from the B-LONG trial for subjects who received weekly prophylaxis regimens. Individual patient data were used to assign weights and balance subjects from PROLONG-9FP with subjects from B-LONG on baseline disease severity, age, prior FIX regimen, and body mass index (BMI). Six efficacy outcomes were analyzed including annualized bleeding rate (ABR), annualized spontaneous bleeding rate (AsBR), annualized joint bleeding rate (AjBR), and the proportion of subjects without bleeding events (for total, spontaneous, and joint bleeding events). After adjustment for baseline disease severity, age, prior FIX regimen, and BMI, rIX-FP was associated with a statistically significant decrease in AsBR (rate ratio [RR] 0.42; 95

Introduction rVIII-SingleChain, a recombinant factor VIII (rFVIII), has demonstrated safety and efficacy in patients with hemophilia A in clinical trials and real-world evidence. This analysis aimed to estimate the potential budget impact of increasing the usage of rVIII-SingleChain for the prophylactic treatment of hemophilia A over 3 years in Italy.Methods Patients with moderate and severe hemophilia A receiving prophylaxis were included in the analysis. Epidemiological data were obtained from published literature. Mean product consumption and mean annual bleeding rate for rVIII-SingleChain, rFVIIIFc, octocog alfa and BAY 81-8973 were based on pooled real-world data from Italy, Germany and US. A budget impact model has been developed in order to compare two scenarios: a base-case scenario where current rVIII-SingleChain shares are kept constant over 3 years and an alternative scenario where rVIII-SingleChain shares increase by taking from other rFVIII products. Analysis 1 was based on the current Italian list prices and Analysis 2 considered current regional acquisition prices for both scenarios.Results Annually, adult patients treated with rVIII-SingleChain prophylaxis are expected to consume 324,589 units per patient, resulting in annual costs of €240,196 per patient. In Analysis 1, comparing the base case (constant market share of 9% rVIII-SingleChain over time) with the alternative scenario (higher rVIII-SingleChain market share and increasing from 15% in the first year to 25% in the third year), the total expenditure for prophylaxis using rFVIII products is expected to decrease by €1.4 million in Year 1, by €3.1 million in Year 2 and by €5.4 million in Year 3. In Analysis 2 based on regional prices, the results remained consistent.Discussion/Conclusion This analysis suggests that increasing utilization of rVIII-SingleChain in hemophilia A patients may lead to cost savings as a result of reduced consumption with uncompromised efficacy in bleed protection.

Objective To evaluate real-world annualized bleeding rates (ABRs), dosing frequency, and factor consumption of four recombinant FVIII (rFVIII) products using pooled data from centers in the US, Germany, and Italy. Methods De-identified patient medical chart data were collected from 48 hemophilia treatment centers in the US, Germany, and Italy. Patients included in this analysis had hemophilia A and were treated with rVIII-SingleChain, rFVIIIFc, octocog alfa, or BAY 81-8973 for >= 12 weeks. Where possible, patient selection considered age and disease severity in order to balance patient groups across products. Summary statistics were presented descriptively by product for dosing frequency, consumption, ABR/annualized spontaneous bleeding rate (AsBR), and corresponding percentage of patients with zero bleeds. Logistic regression was performed for patients with zero bleeds or zero spontaneous bleeds (vs. patients with any such bleeds). Generalized linear model regression was performed for ABR, AsBR, and consumption. All regression models included the product variable for comparison as well as additional independent variables for adjustment (age, weight, severity, and country for the consumption model, with the addition of consumption for the bleeding outcomes models). Results Overall, 616 patients were included (rVIII-SingleChain, n = 129; rFVIIIFc, n = 159; octocog alfa, n = 181; BAY 81-8973, n = 147). Dosing frequency was <= 2 times a week for 65.9%, 75.5%, 25.4%, and 40.1% of patients treated with rVIII-SingleChain, rFVIIIFc, octocog alfa, and BAY 81-8973, respectively. ABRs were not significantly different among products, with mean (median) values of 1.1 (0.0), 1.0 (0.0), 1.4 (1.0), and 1.9 (1.0) for rVIII-SingleChain, rFVIIIFc, octocog alfa, and BAY 81-8973, respectively. The percentage of patients with zero bleeds was comparable between rVIII-SingleChain and rFVIIIFc (59.7% vs. 62.3%; p =.916) and significantly higher for rVIII-SingleChain compared with octocog alfa (p <.001) and BAY 81-8973 (p =.003). Comparison of mean weekly consumption showed: rVIII-SingleChain (83.0 IU/kg/week) vs. rFVIIIFc (96.9; p =.055) and significantly lower for rVIII-SingleChain vs. octocog alfa (108.6; p <.001) and BAY 81-8973 (104.3; p =.001). The median values for weekly consumption were 85.7, 90.1, 100.1, and 98.5 IU/kg/week for rVIII-SingleChain, rFVIIIFc, octocog alfa, and BAY 91-8973, respectively. Similar trends were observed for all outcomes when analyzing the subgroups of patients aged >= 12 years and patients with severe disease (all age and >= 12 years). Conclusions rVIII-SingleChain prophylaxis may provide improved bleed protection, less frequent dosing, and lower consumption compared with standard-acting FVIII products, and comparable protection and consumption to the other long-acting FVIII product, in patients with hemophilia A.