Biogen, one of the world’s oldest independent biotechnology companies, announced that new clinical data support the long-term safety and efficacy of Alprolix [Coagulation Factor IX (Recombinant), Fc Fusion Protein] in people with severe haemophilia B treated for up to two years.
Participants in the phase 3, open-label extension study, B-YOND, maintained low bleeding rates with one to two week prophylaxis regimens, according to data from an interim analysis. Investigators presented these interim results for the first time at the 67th annual meeting of the National Haemophilia Foundation (NHF) in Dallas.
B-YOND is a multi-year study for people with severe haemophilia B who completed the phase 3 pivotal B-LONG or Kids B-LONG studies. In this interim analysis, the median time on Alprolix during B-YOND was 27.6 months for adults and adolescents (n=93), and 47.7 weeks for children under age 12 (n=23). The study’s primary endpoint is inhibitor development, and no inhibitors have been reported to-date. There were three prophylactic dosing options for adult, adolescent, and paediatric participants in the B-YOND trial – weekly, individualised, and modified prophylaxis. An episodic treatment arm was also available for adult and adolescent patients.
“We believe B-YOND will play an important role in helping us understand this therapy’s clinical profile over the long term,” said Amy Shapiro, co-founder and medical director of the Indiana Haemophilia and Thrombosis Center. “Study participants receiving prophylactic treatment with intervals of one to two weeks between infusions continue to experience low bleeding rates during this ongoing extension study.”
Alprolix is a recombinant clotting factor IX therapy designed to have prolonged circulation in the body. According to the interim analysis, adults and adolescents treated prophylactically maintained protection against bleeding episodes with infusions every one to two weeks. These participants had overall median annualised bleeding rates (ABR) of 2.28 for weekly prophylaxis (20-100 IU/kg of Alprolix every seven days), 2.25 for individualised prophylaxis (100 IU/Kg of Alprolix every 8 to 16 days, or twice-monthly) and 2.42 for modified prophylaxis (personalised dosing if optimal prophylaxis could not otherwise be achieved). In contrast, people receiving on-demand therapy, or treatment when a bleeding episode occurred, had a median ABR of 11.27.
The median overall ABR was zero for children under age six who received weekly prophylaxis (n=9). For children between six to 12 years old, median overall ABRs were 2.65 (n=10), 2.37 (n=5) and 3.13 (n=1) in weekly, individualised and modified prophylaxis regimens, respectively. In each age group, the median average weekly dose for participants previously on prophylaxis was similar for individuals in the weekly and individualised treatment arms.
Safety results were typical of the haemophilia B populations studied. The most common adverse events (incidence of greater than or equal to five per cent) included headache, common cold and vomiting for adults and adolescents. For children under age 12, falls, common cold and seasonal allergy were the most common adverse events.
In B-YOND, participants can change between treatment groups at enrollment, and at any time during the study. Most adult and adolescent participants remained in the same treatment group during B-YOND that they had participated in during B-LONG. The majority of children under age 12 stayed on once-weekly treatment (78 per cent). Adults and adolescents were able to achieve a median dosing interval of 6.9 days in the modified prophylaxis arm, and 13.7 days in the individualised prophylaxis arm, while maintaining low ABRs.
From the beginning of B-LONG or Kids-B-LONG until the B-YOND interim data analysis, the cumulative median time on Alprolix was 171.6 weeks for adults and adolescents, and 95.3 weeks for children under age 12.
“The safety and efficacy of Alprolix with extended-interval prophylaxis dosing has been established across a robust clinical development programme, where we consistently have observed low overall bleed rates, as well as low rates of spontaneous and joint bleeds,” said Kate Dawson, vice president, U.S. Medical Affairs at Biogen.
“These results of the B-YOND study provide additional insights supporting the efficacy and safety profile of Alprolix in adults and children with haemophilia B.”
B-YOND enrolled 116 males, including 93 participants (81 percent) who completed B-LONG, and 23 (100 per cent) of those who completed Kids B-LONG. Secondary endpoints of the B-YOND study include ABRs (including spontaneous joint bleeding rates) per participant and treatment exposure days per participant. Additional outcomes are incidence of adverse events and serious adverse events, and evaluation of treatment of a bleeding episode (number of infusions, dose per infusion).
Alprolix, the first recombinant clotting factor therapy with prolonged circulation in the body, is approved in the United States, Canada, Australia and Japan. It is indicated in the United States for the control and prevention of bleeding episodes, perioperative (surgical) management and routine prophylaxis in adults and children with haemophilia B. Alprolix is not indicated for immune tolerance induction therapy, which is a treatment for people with inhibitors.
Introduced in the US in May 2014 and Japan in September 2014, Alprolix provides protection from bleeding episodes with the potential to extend the interval between prophylactic infusions. The therapy was developed using a process called Fc fusion, which is designed to prolong a therapy’s circulation in the body using a naturally occurring pathway. While Fc fusion has been used for more than 15 years, Biogen is the only company to apply it to the treatment of haemophilia.