Positive Efficacy and Safety Results Reported From Phase III Pediatric Study of Eloctate (rFVIII-Fc) for Hemophilia
Twice-weekly prophylactic dosing maintains low bleeding rates
Positive results have been reported from a phase III clinical study that evaluated the safety and efficacy of Eloctate (Biogen Idec/Swedish Orphan Biovitrum AB), an investigational recombinant factor VIII Fc fusion protein product candidate, in children with severe hemophilia A.
Efficacy analyses showed that twice-weekly prophylactic dosing with Eloctate maintained low bleeding rates in children.
Eloctate was developed using a process called Fc fusion and is designed to prolong the circulation of infused clotting factor in the body.
The Kids A-LONG trial was the first study to evaluate a long-lasting, investigational hemophilia therapy in children under 12 years of age. The phase III open-label study involved 71 boys with severe hemophilia A (factor VIII activity less than 1 IU per dL, or 1%), with at least 50 prior exposure days to factor VIII therapies. Overall, 67 participants (94%) completed the study (33 under 6 years of age and 34 aged 6 to 11 years). The average time participants spent in the study was 25 weeks, and 61 participants received Eloctate infusions on at least 50 separate days (exposure days) to assess the development of inhibitors.
All of the participants were initially treated with twice-weekly prophylactic infusions of Eloctate (25 IU/kg on day 1 and 50 IU/kg on day 4). The investigators could adjust the dose or interval based on individual response. Approximately 90% of the study participants were receiving twice-weekly dosing at the end of the study.
The trial investigated the safety, efficacy, and pharmacokinetics of Eloctate in previously treated children under 12 years of age with severe hemophilia A. The primary objective was to evaluate the frequency of inhibitor (neutralizing antibody) development, and none was detected. Secondary endpoints included the overall and spontaneous annualized bleeding rates (ABRs), or the projected number of yearly bleeding episodes, and the number of infusions used to prevent and treat bleeding episodes.
In the study, the relative increase in half-life in children with severe hemophilia A was consistent with the 1.5-fold increase in half-life seen in the A-LONG trial of adults and adolescents. Children treated prophylactically with Eloctate had an overall median ABR of 2.0 and a median ABR for spontaneous bleeds of 0.0. Forty-six percent of participants in the study experienced zero bleeding episodes. Overall, 93% of bleeding episodes were controlled by one or two infusions of Eloctate. Additional analyses of the Kids A-LONG study are ongoing.
Eloctate is an investigational, recombinant clotting factor therapy developed for the treatment of hemophilia A by fusing factor VIII to the Fc portion of immunoglobulin G subclass 1 (IgG1), a protein commonly found in the body. It is believed that this enables Eloctate to use a naturally occurring pathway to prolong the time therapy remains in the body. While Fc fusion has been used for more than 15 years, Biogen Idec is the only company to apply it to the treatment of hemophilia.
Regulatory applications for the approval of Eloctate are currently under review in several countries, including the U.S.
Source: Biogen Idec; April 10, 2014.