Clinical Trials

Date: 2015-06-18

Type of information: Presentation of results at a congress

phase: 3 - pediatric study

Announcement: presentation of results at the International Society on Thrombosis and Haemostasis (ISTH) 2015 congress taking place in Toronto, Canada, 20-25 June 2015

Company: BiogenIdec (USA) Swedish Orphan Biovitrum - SOBI (Sweden)

Product: Alprolix® (eftrenonacog alfa - long-lasting recombinant Factor IX Fc fusion protein (rFIXFc) - BIIB 029)

Action mechanism:

• fusion protein. Recombinant FIXFc is a clotting factor developed using Biogen Idec's novel and proprietary monomeric Fc fusion technology, which makes use of a natural pathway to recycle rFIXFc in circulation and enable it to remain in the body longer. With this technology, rFIXFc is designed to provide long-lasting protection from bleeding and reduce the treatment burden associated with hemophilia B, which currently requires more than 100 injections annually for prophylaxis with commercially-available Factor IX products.

Disease: hemophilia B

Therapeutic area: Hematologic diseases - Genetic diseases - Rare diseases

Country: USA, Australia, Hong Kong

Trial details:

• The Kids B-LONG study is an open-label, multicenter study designed to evaluate the safety, pharmacokinetics and efficacy of rFIXFc in the prevention and treatment of bleeding episodes in previously-treated pediatric patients with hemophilia B. The study has included approximately 30 male patients under the age of 12  with severe hemophilia B (factor IX activity equal to or less than 2 IU per dL, or 2 percent) with at least 50 prior exposure days to factor IX therapies. The study was conducted at 16 hemophilia treatment centers in six countries. Overall, 27 participants (90 percent) completed the study. The median time participants spent in the study was 49.4 weeks, and 24 participants received Alprolix® infusions on at least 50 separate days (exposure days). The primary outcome measure is the frequency of inhibitor development over an approximately 50-week treatment period and at least 50 exposure days to rFIXFc. Secondary outcome measures include the number of annualized bleeding episodes and assessments of response to treatment over the same time period. (NCT01440946).

Latest news:

• • On June 18, 2015, Swedish Orphan Biovitrum (Sobi) and  Biogen announced that they will present 23 company-sponsored platform and poster presentations at the International Society on Thrombosis and Haemostasis (ISTH) 2015 congress taking place in Toronto, Canada, 20-25 June 2015. Data presented include a late-breaking platform presentation from the Kids B-LONG study detailing the safety and efficacy of Alprolix/rFIXFc [Coagulation Factor IX (Recombinant), Fc Fusion Protein] in children with haemophilia B. This is the first time full results from the Kids B-LONG study will be publicly presented.
• Alprolix-focused abstracts  are: Study of recombinant factor IX Fc fusion protein in children with haemophilia B and Indirect comparisons of factor consumption, bleeding rates, and infusion frequencies during routine prophylaxis with recombinant factor IX Fc fusion protein and other recombinant factor IX products - Poster #171.
• • On February 27, 2015, Biogen Idec and Swedish Orphan Biovitrum (Sobi) announced positive top-line results of the Kids B-LONG Phase 3 clinical study that evaluated the safety, efficacy and pharmacokinetics of Alprolix® [Coagulation Factor IX (Recombinant), Fc Fusion Protein] in children under age 12 with severe hemophilia B. Alprolix® was generally well tolerated and no inhibitors (neutralizing antibodies that may interfere with the activity of the therapy) were detected during the study. In this study, once-weekly prophylactic dosing with Alprolix® resulted in low bleeding rates. Alprolix® is the only approved hemophilia B therapy with prolonged circulation in the body. The successful completion of Kids B-LONG supports applications for pediatric indications in several geographies and is an important step in seeking marketing authorization for ALPROLIX in Europe. The European Medicines Agency requires the inclusion of pediatric study data in the initial marketing application for a new hemophilia therapy. Interim results of the Kids B-LONG study helped support the U.S. approval of Alprolix® for use in children. “According to published studies, prophylactic treatment for children with severe hemophilia is recommended because it is associated with proven clinical benefits. However, frequent administration schedules can be burdensome for children and their caregivers,” said Aoife Brennan, M.D, vice president of hematology clinical development at Biogen Idec. “These data will enable regulatory filings in Europe later this year as well as support pediatric indications in other countries, with the potential to help address a critical need among children with hemophilia B.” Kids B-LONG investigated the safety, efficacy, and pharmacokinetics (measurement of the presence of the drug in a person’s body over time) of Alprolix® in previously treated children under age 12 with severe hemophilia B. The study’s primary endpoint was to evaluate the occurrence of inhibitor development. Secondary endpoints included the overall and spontaneous annualized bleeding rates (ABR), which is the estimated number of yearly bleeding episodes, and the number of infusions used to treat bleeding episodes. In the study, children treated prophylactically with Alprolix® had an overall median ABR of 1.97. The median ABR for spontaneous joint bleeds was zero. Approximately 33 percent of participants in the study experienced zero bleeding episodes. Overall, 91.7 percent of bleeding episodes were controlled by one or two infusions of Alprolix®. The terminal half-life of Alprolix® in the study was 66.5 hours for children under six and 70.3 hours for children six to less than 12 years of age. Additional analyses of the Kids B-LONG study are ongoing, and detailed results will be presented at a future scientific meeting. No inhibitors to Alprolix®were detected during the study. Alprolix® was generally well tolerated and no cases of serious allergic reactions or vascular thrombotic events were reported in any participants, all of whom had been previously treated with other commercially available factor IX products. No serious adverse events were determined by any investigator to be related to the drug. One adverse event, decreased appetite, was considered related to Alprolix® treatment and was reported in one participant. No participant discontinued the study due to an adverse event after receiving Alprolix®. The pattern of treatment-emergent adverse events reported was consistent with the population studied and generally consistent with results seen in adolescents and adults in the pivotal Phase 3 B-LONG study. • On July 5, 2012, Biogen Idec and Swedish Orphan Biovitrum announced the initiation of two global pediatric clinical trials of the companies’ long-lasting recombinant Factor IX Fc fusion protein (rFIXFc) in hemophilia B. rFIXFc is a fully-recombinant clotting factors developed using Biogen Idec\'s novel and proprietary monomeric Fc-fusion technology, which makes use of a natural mechanism to recycle rFIXFc 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 first patient has been dosed in the rFIXFc pediatric study, and global registration studies of rFIXFc are ongoing in previously-treated patients with severe hemophilia B aged 12 years and over, with data readouts expected in the second half of the year.

Is general: Yes