phase: pediatric study
Company: BiogenIdec (USA) Swedish Orphan Biovitrum - SOBI (Sweden)
Product: Eloctate® (long-lasting recombinant Factor VIII Fc fusion protein - rFVIIIFc)
- protein. Eloctate® is an investigational, recombinant clotting factor therapy developed for hemophilia A by fusing factor VIII to the Fc portion of immunoglobulin G subclass 1, or 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.
Disease: hemophilia A
area: Hematological diseases - Genetic diseases
- Kids A-LONG was a global, open-label, multi-center Phase 3 study involving 71 boys with severe hemophilia A (factor VIII activity less than 1 IU per dL, or 1 percent) with at least 50 prior exposure days to factor VIII therapies. The study was conducted at 23 hemophilia treatment centers in eight countries. Overall, 67 participants (94 percent) completed the study (33 under six years old and 34 six to 11 years old). 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 inhibitor development.
All study participants were to be initially treated with twice-weekly prophylactic infusions of Eloctate® [25 IU/kg day 1, 50 IU/kg day 4]. Study investigators could adjust the dose or interval based on individual response. Approximately ninety percent of study participants were on twice-weekly dosing at the end of the study. The primary outcome measure is the frequency of inhibitor development over an approximately 26-week treatment period and at least 50 exposure days to rFVIIIFc. Secondary outcome measures include the number of annualized bleeding episodes and assessments of response to treatment over the same time period. (NCT01458106).
- • On April 10, 2014, Biogen Idec and Swedish Orphan Biovitrum (SOBI) have released positive top-line results of the Kids A-LONG Phase 3 clinical study that evaluated the safety and efficacy of Eloctate®, an investigational recombinant factor VIII Fc fusion protein product candidate, in children with severe hemophilia A. Eloctate® was generally well-tolerated and no inhibitors (neutralizing antibodies that may interfere with the activity of the therapy) were detected. Efficacy analyses showed twice-weekly prophylactic dosing with Eloctate® maintained low bleeding rates in children.
Kids A-LONG is the first study to evaluate a long-lasting, investigational hemophilia therapy in children under 12 years old. Eloctate® was developed using a process called Fc fusion and is designed to prolong the circulation of infused clotting factor in the body. The successful completion of this study will support applications for pediatric indications globally and is an important step to obtaining marketing authorization in Europe.
- Kids A-LONG investigated the safety, efficacy and pharmacokinetics (measurement of the presence of the drug in a person’s body over time) of ELOCTATE in previously treated children under 12 years old with severe hemophilia A. The primary endpoint of the study was to evaluate the frequency of inhibitor (neutralizing antibody) development and none were detected. Secondary endpoints included the overall and spontaneous annualized bleeding rates (ABR), or 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 study 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, ninety three percent of bleeding episodes were controlled by one to two infusions of Eloctate®. Additional analyses of the Kids A-LONG study are ongoing, and the companies plan to present detailed results at a future scientific meeting.
- • On July 5, 2012, Biogen Idec and Swedish Orphan Biovitrum have announced the initiation of a global pediatric clinical trials of the companies’ long-lasting recombinant Factor VIII Fc fusion protein (rFVIIIFc) in hemophilia A. rFVIIIFc is a fully-recombinant clotting factor developed using Biogen Idec's novel and proprietary monomeric Fc-fusion technology, which makes use of a natural mechanism to recycle rFVIIIFc in the circulation in the body. Biogen Idec and Sobi are studying this technology to see whether it extends half-life and enables the proteins to last longer in the body than commercially-available factor products. The rFVIIIFc pediatric study is now actively recruiting patients. Global registration studies of rFVIIIFc are ongoing in previously-treated patients with severe hemophilia A aged 12 years and over, with data readouts expected in the second half of the year.