At the recent World Federation of Haemophilia’s (WFH’s) world congress in Buenos Aires, Argentina, Octapharma AG sponsored a symposium entitled ?Modern Treatment Options for von Willebrand Disease (VWD) and Haemophilia B ? What are the Benefits for the Patients??, which took place on July 12, 2010. Wilate?.

The new concetrate is the first double-virus-inactivated VWF/FVIII, high-purity concentrate, utilising the solvent/detergent (S/D) process and Permaheat – a special terminal dry-heating (TDH) step. The selected purification processes isolate the VWF/FVIII complex under highly protein-protecting conditions, resulting in a 1:1 ratio of VWF:RCo (ristocetin cofactor) to FVIII activity that is similar to normal plasma. No albumin is added as a stabiliser. Wilate? is exclusively derived from large pools of human plasma collected in FDA-approved plasma donation centres. Wilate? contains a VWF triplet structure and content of high-molecular-weight multimers similar to normal human plasma. Acknowledging the superior viral safety profile, US-FDA recently granted orphan drug status to Wilate?. The product is registered in more than 40 countries worldwide, including most EU countries, the US, Canada, Australia, Brazil and Russia.

The next-generation factor better reflects the normal physiological condition as compared to conventional concentrates. This well-attended, highly educational symposium addressed the effective management of VWD with Wilate? in the setting of surgery, the outstanding biochemical and pharmacokinetic profile of Wilate? to improve treatment, monitoring and dosing, and gave insights into the linking of experiences with prophylaxis in VWD with haemophilia A and B.

?We are excited and enthusiastic about our next-generation VWF/FVIII product, Wilate?, which better reflects normal human plasma with a 1:1 ratio of the VWF to FVIII coagulation factors?, said Octapharma Vice Chairman Kim Bj?rnstrup. “The increased clinical efficacy and safety profiles provided by Wilate?, as compared to older generation products, reflect our vision of a more convenient on-demand and prophylactic therapy with minimised thromboembolic risks developed especially for VWD”, added Dr Olaf Walter, Head of Octapharma`s Haematology Business Unit.

Dr Paul Giangrande (Haemophilia Centre and Thrombosis Unit Churchill Hospital, Oxford, United Kingdom) chaired the symposium, and introduced his clinical vision for what one would expect from a next-generation product in the treatment of VWD. The unique combination of factors provided by Wilate?, he pointed out, includes high quality protein reflected by high coagulation activity and pure native VWF/FVIII complex product, no albumin stabiliser, an intact VWF triplet structure and physiological multimeric pattern profile, completed with assured viral safety measures during manufacture. Dr Giangrande then referred to the recent 2009 Food and Drug Administration’s (FDA) orphan drug status approval for Wilate? in the treatment of VWD.

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Dr Mario von Depka (Werlhof ? Institute Hannover, Germany) discussed haemostatic management of surgical procedures in VWD patients. He presented results from a meta-analysis and from his own centre?s experience with Wilate? during surgical procedures that highlighted efficacy and thromboembolic safety of this next-generation concentrate. Dr von Depka pointed out that Wilate? showed excellent or good efficacy in more than 96% of surgeries. As accumulation of FVIII has been seen with some VWF/FVIII concentrates, Dr von Depka focused particularly on monitoring on FVIII levels after concentrate administration. ?Elevated FVIII levels?, he pointed out, ?are a known risk for thromboembolism?. He noted from own experience, as well as the published studies, that even after multiple dosing with Wilate? there was no accumulation of FVIII, adding that this is probably due to the 1:1 ratio of VWF to FVIII.

In line with these findings, Dr Craig Kessler (Georgetown University in Washington, D.C., USA) presented results of a controlled crossover study assessing the pharmacokinetic properties of two VWF/FVIII concentrates in patients with VWD. Main results from this study supported the clinical experience of Dr von Depka, who observed no accumulation of FVIII levels after repeated dosing by showing parallel decay of plasma levels for the VWF and FVIII coagulation factors for Wilate?.

In sharp contrast to this was an unexpected plateau in FVIII after administration of the older-generation product, Humate-P? (CSL Behring). Whereas the half life of VWF for both concentrates was comparable, the FVIII half life showed significant prolongation in the comparator product. Dr Kessler pointed out that the pharmacokinetic profile of Wilate? may be essential for the observed absence of FVIII accumulation in patients. In the second part of his talk, Dr Kessler presented an improved method for von Willebrand factor level monitoring in VWD patients using a new assay that provides increased sensitivity and optimized level of detection, which is especially important for severe cases of VWD with strongly reduced levels of VWF (Type 3).

Dr Christoph Kannicht (Octapharma PCR&D, Molecular Biochemistry, Berlin, Germany) presented the latest update on VWF biochemical characteristics that affect functionality, focusing on the role of VWF triplet structure resulting from the activity of metalloprotease ADAMTS13. He noted that there are ?significant differences between fractions with different sub-band distribution? and that sub-band distribution affects VWF-mediated platelet adhesion. Dr Kannicht showed that distribution of VWF multimers and triplet structure in Wilate? closely resemble that of normal human plasma and that ?Wilate? was proven to provide fully functional VWF?. He showed that low levels of ADAMTS13 in Wilate?,resulting from the high purity of this product, are important for a fully functional product.

Another area of great importance for patients with VWD is the use of prophylactic treatment, especially in children, in whom long-term effects of early prophylaxis have been documented. Dr Rolf Ljung (Lund University, Lund, Sweden) presented data on the Swedish experience with prophylaxis in children with VWD. The results from clinical studies showed that the number of bleeding episodes was reduced by up to 90% while on prophylaxis, for example, with Wilate?. ?What was encouraging?, he added, ?is that children who started prophylaxis at an early age did not develop arthropathy?. Prophylactic treatment with another plasma-derived product, Octanine? F, was shown to be effective in children with haemophilia B, another understudied group of patients. Dr Ljung acknowledged that ?the obstacle to prophylactic therapy is always the cost and the resources? but that ?you can do quite a lot with prophylactic therapy with limited resources?. He pointed out that it is more cost-effective to treat more often with a lower dose than less frequently with a higher dose. He stressed that, when resources are limited, children should always have the first priority and that prophylaxis should be started early, at the age of 1 or 2, as the evidence shows this may also protect from more serious bleeding later on.

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