Date: 2016-10-28
Type of information: Reimbursement
Product name: Alprolix™
Compound: recombinant Factor IX Fc fusion protein (rFIXFc) - eftrenonacog alfa
Therapeutic area: Hematological diseases - Genetic diseases - Rare diseases
Action mechanism: fusion protein/coagulation factor. Recombinant FIXFc (Alprolix™) 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.
Company: BiogenIdec (USA - MA) Swedish Orphan Biovitrum (Sobi) (Sweden)
Disease: hemophilia B
Latest news: * On October 28, 2016, Swedish Orphan Biovitrum announced that the Swiss Agency for Therapeutic Products, Swissmedic, has approved Alprolix® (eftrenonacog alfa) for the treatment of haemophilia B. Alprolix is the only recombinant factor IX Fc Fusion protein therapy approved in Switzerland for the treatment of haemophilia B. * On October 3, 2016, Swedish Orphan Biovitrum announces that the European Commission has approved the transfer of the marketing authorisation for Alprolix® (eftrenonacog alfa)for the treatment of haemophilia B, from Biogen to Sobi, making Sobi the marketing authorisation holder (MAH) in the EU. The EC has also approved the transfer of the orphan designation to Sobi. As MAH, Sobi will assume full regulatory responsibility for Alprolix® in the EU. * On September 26, 2016, Swedish Orphan Biovitrum announces that Alprolix® (eftrenonacog alfa), a recombinant human factor IX Fc-fusion protein with extended half-life for the treatment of haemophilia B, has now been approved for reimbursement across the UK. National Health Service (NHS) England has confirmed reimbursement alongside Scotland, Wales and Northern Ireland where Alprolix® is already reimbursed. Alprolix® is also approved for reimbursement in Germany and the Netherlands. * On June 6, 2016, following the recent approval of the extended half-life therapy Alprolix® by the European Commission for the treatment of haemophilia B, Sobi announced the first sales of Alprolix® in Germany. * On May 13, 2016, Swedish Orphan Biovitrum (Sobi) and Biogen announced that the European Commission (EC) has approved Alprolix® (rFIXFc), their extended half-life therapy, for the treatment of haemophilia B in all 28 European Union (EU) member states and maintained its orphan designation. Alprolix® is indicated for both on-demand and prophylaxis treatment of people with haemophilia B in all ages. Prophylactically, it can be administered with an initial dose every seven days or every 10 days with the ability to adjust the dosing interval based on individual response. * On February 26, 2016, Swedish Orphan Biovitrum (Sobi) and Biogen received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommending that marketing authorisation be granted for Alprolix® (rFIXFc), a recombinant factor IX Fc fusion protein therapy for the treatment of haemophilia B. If approved, Alprolix would be among the first therapies in the European Union (EU) to offer people living with haemophilia B prolonged protection against bleeding episodes with prophylactic dosing intervals. The positive opinion was based on results from two global, Phase 3 clinical trials that demonstrated the efficacy, safety and pharmacokinetics of Alprolix for haemophilia B: the pivotal B-LONG study for previously treated adults and adolescents, and the Kids B-LONG study for previously treated children under age 12. * On December 22, 2015, Swedish Orphan Biovitrum (Sobi) has received orphan drug designation in Switzerland for its extended half-life haemophilia drug candidate Alprolix® (rFIXFc) developed for the treatment of haemophilia B. The World Federation of Hemophilia global survey conducted in 2013 estimates that approximately 28,430 people are currently diagnosed with haemophilia B worldwide. * On June 26, 2015, Biogen and Swedish Orphan Biovitrum (Sobi) announced that the European Medicines Agency (EMA) has accepted the Marketing Authorization Application (MAA) of Alprolix® (rFIXFc), a recombinant factor IX Fc fusion protein product candidate for the treatment of hemophilia B. This validation signifies the initiation of the EMA’s review process. The MAA includes results from two global, Phase 3 clinical trials examining the efficacy, safety and pharmacokinetics (a measure of the presence of the therapy in a person’s body over time) of ALPROLIX for hemophilia B: the pivotal B-LONG study for previously treated adults and adolescents, and Kids B-LONG study for previously treated children under age 12. * On March 28, 2014, Biogen Idec has announced that the FDA has approved Alprolix™ [Coagulation Factor IX (Recombinant), Fc Fusion Protein] for the control and prevention of bleeding episodes, perioperative (surgical) management and routine prophylaxis in adults and children with hemophilia B. The therapy is shown to reduce bleeding episodes with prophylactic (protective) infusions starting at least a week apart. The approval of Alprolix™ is based on results from the global, Phase 3 B-LONG study, as well as interim pharmacokinetic (measurement of the presence of the therapy in a person’s body over time) and safety data from the Phase 3 Kids B-LONG study. B-LONG study results showed that adults and adolescents with severe hemophilia B achieved prevention or reduction of bleeding episodes with prophylactic infusions at least a week apart. The study included two prophylaxis regimens – the weekly prophylaxis arm and the individualized-interval prophylaxis arm, in which the dosing interval started at once every 10 days. The overall median dosing interval with individualized-interval prophylaxis was 12.5 days; during the last six months of the study, the median interval was 13.8 days. More than 90 percent of all bleeding episodes were controlled by a single Alprolix™infusion. No participants in the B-LONG study developed inhibitors (neutralizing antibodies that may interfere with the activity of the therapy) to Alprolix™. There were no reports of vascular clots or serious allergic reactions. Across the routine prophylaxis and on-demand therapy arms, adverse reactions were reported in 8.4 percent of participants. These adverse reactions included headache, oral paresthesia (abnormal sensation in the mouth), dizziness, dysgeusia (taste alteration), breath odor, fatigue, infusion site pain, palpitations, obstructive uropathy (an obstructing clot in the urinary collecting system) and hypotension (low blood pressure). Each event occurred in two or fewer study participants. An interim analysis from an ongoing, multi-center Phase 3 pediatric study – Kids B-LONG –showed no inhibitors were detected, and the increase in half-life (a measure of the time therapy remains in the body) seen with Alprolix™ was consistent with data reported in adults and adolescents. Biogen Idec plans to make Alprolix™ commercially available to people with hemophilia B in the United States in early May. * On March 21, 2014, Biogen Idec has announced that Health Canada has approved Alprolix™ [Coagulation Factor IX (Recombinant), Fc Fusion Protein], for the control and prevention of bleeding episodes and routine prophylaxis in adults, and children aged 12 and older, with hemophilia B. This is the first regulatory approval worldwide for Alprolix™, which is currently under review by regulatory authorities in several other countries, including the United States, Australia and Japan. The Health Canada approval of Alprolix™ is based on results from the global, Phase 3 B-LONG study, the largest registrational study in hemophilia B ever completed. It demonstrated that Alprolix™ safely and effectively prevented, or reduced, bleeding episodes with prophylactic infusions given once weekly or once every 10-14 days in adults and adolescents with severe hemophilia B. In addition, more than 90 percent of all bleeding episodes were controlled by a single Alprolix™infusion. Biogen Idec and Sobi are partners in the development and commercialization of rFIXFc in hemophilia B and rFVIIIFc in hemophilia A.
Alprolix® is indicated for both on-demand and prophylaxis treatment of previously treated haemophilia B patients. For initiation of prophylaxis one dose every seven days or every 10 days can be administered, with the ability to adjust the dosing interval based on individual response.
* On December 2, 2013, Sobi's partner Biogen Idec has announced that the FDA has extended the initial Prescription Drug User Fee Act (PDUFA) date for its review of the Biologics License Application (BLA) for Alprolix™, the company's investigational long-lasting recombinant factor IX Fc fusion protein candidate for hemophilia B. The PDUFA date has been extended by three months, which is the standard extension period. In response to a request from FDA, Biogen Idec submitted additional information related to the validation of a manufacturing step for ALPROLIX. Due to the timing of this submission, the FDA extended the PDUFA date to allow additional time for review of the marketing application.The updated timeline for FDA approval will not impact Sobi's planned European approval timelines.
* On March 4, 2013, Biogen Idec has announced that the FDA has accepted the company’s Biologics License Application (BLA) for the marketing approval of Alprolix™ for the treatment of hemophilia B and granted the company a standard review timeline. Recombinant FIXFc is the first product candidate in a new class of long-lasting clotting factor therapies being developed with the goal of reducing the burden of treatment for hemophilia B. A BLA submission for rFVIIIFc for use in patients with hemophilia A is also on track for filing during the first half of 2013.
* On January 4, 2013, Biogen Idec has announced the company recently submitted a Biologics License Application (BLA) to the FDA for the marketing approval of recombinant factor IX Fc fusion protein (rFIXFc) for the treatment of hemophilia B. rFIXFc is the first product candidate in a new class of long-lasting clotting factor therapies that are being developed with the goals of reducing the burden of treatment for this condition and enhancing protection from bleeding. The regulatory submission was based on results from B-LONG, the largest registrational phase 3 clinical study in hemophilia B to date. Two global pediatric clinical trials have been initiated last July.
Patents:
Submission of marketing authorization application USA : 2013-01-04
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2014-03-28
UE authorization: 2016-05-12
Favourable opinion UE: 2016-02-26
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: OTC status: Other news:
