New objective criteria for evaluating hemostatic efficacy in treatment of VWD

Octapharma USA researchers presented new stringent, objective criteria used in the evaluation of hemostatic efficacy in the treatment of von Willebrand disease (VWD) and reported on their application of these criteria in clinical trials during the recently completed National Hemophilia Foundation (NHF) Annual Meeting. According to the National Institutes of Health VWD is the most common inherited bleeding disorder and occurs in about 1 out of every 100 to 1,000 people.

"We believe these objective criteria will help avoid the potential problems of bias and inconsistencies observed with the previously used subjective analysis," said Octapharma USA President Flemming Nielsen. Octapharma USA is an affiliate of Octapharma AG, one of the largest human protein products manufacturers in the world. The U.S. Food and Drug Administration (FDA) has granted Octapharma orphan drug exclusivity for wilate® (von Willebrand Factor/Factor VIII Concentrate, Human), the first replacement therapy developed specifically for von Willebrand Disease (VWD).

Craig Kessler, M.D., Georgetown University Hospital, Professor of Medicine and Pathology and Director of the Division of Coagulation, noted that in clinical trials applying the most stringent criteria to date – first proposed for the assessment of wilate® – successful control of bleeding was achieved in 84% (95% CI 81.8 to 86.2) of cases. The discussion was part of an NHF poster presentation entitled, "Clinical Efficacy of VWF/FVIII Replacement Therapy Utilizing Subjective vs. Objective Criteria – Improved Accuracy and Comparability of Results in Clinical Trials."

Products previously used to treat VWD were evaluated on a subjective four-point Likert scale with efficacy ranging from "none" to "excellent."  Researchers added a more stringent evaluation criteria in combination with the Likert scale during clinical trials for wilate®. The FDA has approved wilate® for the treatment of spontaneous or trauma-induced bleeding episodes in patients with severe VWD as well as in patients with mild or moderate forms of the illness in whom the use of desmopressin is known or suspected to be ineffective or contraindicated.

Promoting a scientific dialogue regarding recent research findings, Octapharma USA also provided a poster presentation entitled, "The Development of the First Recombinant FVIII from a Human Cell – Functional Properties and Differences from Currently Available Recombinant Factor VIII Products." The research report reviewed the functional properties of the first recombinant factor VIII concentrate produced in a human cell line. Today, the development of antibodies against infused FVIII represents the most devastating complication in modern Hemophilia A replacement therapy. The human glycosylation pattern in Human-cl rhFVIII should make it possible to avoid potentially immunogenic epitopes as expressed by hamster cells. This may result in improved safety and long-term reduced immunogenicity of Human-cl rhFVIII, which is currently investigated in ongoing clinical studies.

The final Octapharma NHF poster presentation was "Results of a Prospective, Randomized, Crossover Study Investigating the Pharmacokinetic (PK) Properties of VWF/FVIII Concentrates in Subjects with Inherited von Willebrand Disease (VWD)." Understanding PK profiles of VWF/FVIII concentrates is important in the treatment of VWD. The prospective, randomized, open-label, crossover trial investigated the PK characteristics of two plasma-derived (pd)VWF/FVIII concentrates – wilate® [highpurity (HP)] and HumateP® [intermediatepurity (IP)]) in subjects with inherited VWD.

The study confirmed the similarity of the VWF PK properties of the two licensed VWF products in all VWD types, including type 3 subjects.  However, the analysis of FVIII activity in the two products revealed some differences in their PK profiles. Wilate® infusion in type 3 subjects showed an expected exponential decay curve for both VWF:RCo and FVIII:C activities that was parallel over time.  With similar PK-properties for both VWF:RCo and FVIII:C, wilate® demonstrated a more predictable PK profile for both VWF and FVIII, which  may facilitate dosing and laboratory monitoring of VWF replacement in VWD treatment.