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Introduction BAY 81–8973, a full-length recombinant factor VIII for hemophilia A treatment, has been extensively evaluated in previously treated patients in the LEOPOLD (Long-Term Efficacy Open-Label Program in Severe Hemophilia A Disease) clinical trials. Aim To assess BAY 81–8973 efficacy and safety when used for bleed prophylaxis and treatment in previously untreated/minimally treated patients (PUPs/MTPs). Methods In this phase III, multicenter, open-label, uncontrolled study, PUPs/MTPs ( Results Fifty-two patients were enrolled, with 43 patients (mean age: 13.6 months) treated. Median (interquartile range) ABR for all bleeds within 48 hours of prophylaxis infusion was 0.0 (0.0–1.8) among patients without inhibitors (n = 20) and 0.0 (0.0–2.2) among all patients. As expected, inhibitors were the most frequent treatment-related adverse event (high titer: 17 [39.5%] patients; low titer: 6 [13.9%] patients). Six of 12 patients who underwent ITI treatment in the extension phase (high titer [n = 5], low titer [n = 1]) achieved a negative inhibitor titer. Conclusion BAY 81–8973 was effective for bleed prevention and treatment in PUPs/MTPs. The observed inhibitor rate was strongly influenced by a cluster of inhibitor cases, and consequently, slightly higher than in other PUP/MTP studies. Overall, the BAY 81–8973 benefit–risk profile remains unchanged and supported by ongoing safety surveillance. Immune tolerance can be achieved with BAY 81–8973.

SummaryCurrent therapy for haemophilia A is guided by severity of the disease, which in turn is best reflected in patients' endogenous factor VIII activity levels. For patients with severe haemophilia (particularly children), prophylaxis with continuous routine factor replacement has become standard of care in developed countries and is gradually becoming the standard of care in developing countries. The question arises then: what is an appropriate prophylaxis regimen to prevent bleeding events and arthropathy, while also maximizing patient quality of life and taking into consideration the costs of prophylaxis? Should all patients be treated with one standard, fixed prophylaxis regimen, or should prophylaxis be individualised for each patient? If so, what factors need to be considered in choosing the appropriate dose and frequency of factor administration? If prophylaxis is tailored to the individual patient, then patient-related factors (bleeding phenotype, activity profiles, age, joint status) and product-specific factors (half-life of the replacement factor in the individual patient) will determine the choice of regimen, whether it be a fixed-regimen prophylaxis or prophylaxis that is tailored to patient activity and bleeding risk. Regardless of the choice of prophylaxis regimen, for any regimen to be effective, adherence to therapy is key to optimising outcomes.

IntroductionThe goal of prophylactic treatment of hemophilia is to convert the severe form of the disorder into a milder form by administration of factors VIII or IX. The rationale behind this is that chronic arthropathy, the hallmark of hemophilia after repeated bleedings, is less frequent and less severe in moderate hemophilia (i.e., factor VIII or factor IX concentrations of 1% to 4% of normal) than in severe hemophilia (i.e., factor VIII/factor IX concentrations lower than 1% of normal).1 Keep in mind, however, that prophylactic treatment also provides protection from all other forms of hemorrhage that may occur spontaneously or as a result of trivial trauma in the untreated hemophilic child. Today, prophylactic treatment is available to only a few hemophilia patients in the world, although it is recommended by the World Health Organization (WHO) and the World Federation of Haemophilia (WFH): “Since the main goal is to prevent joint bleeding and its sequelae, prophylaxis should be considered optimal management for persons with severe hemophilia A or B (i.e., with basal factor VIII and/or factor IX levels

SummaryWe have detected the mutations in the factor IX genes from all of the haemophilia B patients registered at Malmo haemophilia centre (45) and are currently examining the entire UK haemophilia B population. From these studies we have found 13 base substitutions which have recurred in 1-6 other, presumably unrelated, patients. In order to determine the minimum number of independent repeats of each mutation we have used PCR to examine the five factor IX polymorphisms forming the most informative combinations and we have characterised the haplotype of each patient. Patients with different haplotypes are assumed to be unrelated and thus to carry independent mutations. All but one of the 13 mutations occur in at least 2 haplotypes thus pinpointing 12 mutational hotspots and mutations that can be clearly considered detrimental. Two of the 13 substitutions occur at non-CpG sites.