The Clinical Development of the First Recombinant FVIII From a Human Cell Line.

Abstract 4439 Objective In order to provide a new recombinant FVIII to the hemophilia community with potentially improved features including improved VWF binding and reduced immunogenic potential, a recombinant FVIII produced in a human cell line was developed (human-cl rhFVIII). The requirements for registration of a new recombinant FVIII in Europe are specified in a guideline. In addition, any global development plans need to be discussed with the US FDA. Methods The clinical development plan of human-cl rhFVIII follows the European guideline and the requirements as discussed with the FDA. Here we introduce the first recently started clinical trial with human-cl rhFVIII. It is a prospective, randomized, open, cross-over phase II pharmacokinetic and efficacy/safety trial in 20 patients with severe hemophilia A conducted at one center in Russia. In this trial the pharmacokinetic properties of human-cl rhFVIII will be compared with an established rFVIII product. After a wash-out phase of at least 72 hours patients will be randomly assigned to one of the two products and receive a single dose of 50 IU of FVIII/kg B.W.. Thereafter, blood will be collected at pre-specified time points over 48 hours, followed by a wash-out phase after which the second product will be administered. Subsequently, patients will be prophylactically treated for 6 months with human-cl rhFVIII to document the efficacy and safety of the product. At the end of the study, a second PK assessment with human-cl rh FVIII will be conducted. FVIII:C will be measured with validated one-stage and chromogenic assays. An “Independent Data Monitoring Committee“ will supervise the safety aspects of the trials and will perform an independent adjudication of the hemostatic efficacy assessment. Results Seven patients have been enrolled and followed for 2 – 50 exposure days on prophylactic treatment. The data of the first 7 patients indicate similar PK characteristics for human-cl rhFVIII compared to the established rFVIII. Human-cl rhFVIII was well tolerated and no safety issue has been reported yet. There were two breakthrough bleeds in target joints in two patients that were controlled with one dose of human-cl rhFVIII each. Further patients have been enrolled and updated information will be presented accordingly. Conclusion The novel human-cl rhFVIII has been successfully introduced to patients and appears to have comparable PK characteristics to a well-established marketed rFVIII and seems to be safe and well tolerated in this limited patient group. A first clinical study with human-cl rhFVIII in the US is planned to be initiated soon. Disclosures: Knaub: Octapharma AG: Employment. Zozulya:Octapharma AG: Membership on an entity's Board of Directors or advisory committees.