Patients with congenital Factor XIII A-subunit deficiency will have access to a new recombinant treatment for the disorder beginning early in 2014, following the FDA’s approval of Novo Nordisk A/S’s Tretten (coagulation Factor XIII A-subunit [recombinant]) for routine prophylaxis of bleeding.

With the approval, Tretten has become the only recombinant therapy for FXIII A-subunit deficiency.

Novo acquired the rights to Tretten in 2004 from Zymogenetics Inc., in a deal worth up to $77 million. It paid $15 million up front and agreed to another $62 in potential milestones, with $40 million of that being deadline-based. Zymogenetics also was eligible for royalties on any products containing its Factor XIII. (See BioWorld Today, Oct. 6, 2004.)

Zymogenetics was founded in 1981 and acquired by Novo in 1988. The company operated as Novo’s research arm until Novo spun it out in 2000. It went on to have one of 2002’s most notable initial public offerings in the biotech sector, raising $120 million through the sale of 10 million shares.

Its strength in biologic drugs eventually attracted another buyer. In 2010, Bristol-Myers Squibb Co. bought Zymogenetics, offering $9.75 per share, or about $885 million. (See BioWorld Today, Sept. 9, 2010.)

FXIII A-subunit deficiency is characterized by a susceptibility to bleeding, including intracranial hemorrhage due to a lack of the clotting Factor XIII. It occurs in approximately one in 3 million to 5 million births in the U.S. and, in 2011, there were an estimated 2,014 patients diagnosed worldwide, with about 115 in the U.S.

Novo’s application for Tretten included a Phase III trial in 41 patients showing that, compared to a historical control group, preventive treatment with monthly 35 IU/kg Tretten injections significantly decreased bleeding episodes requiring treatment.

The most common adverse reactions were headache, pain in extremities, injection site pain and increase of D dimer.

Tretten is approved in Canada, where it is marketed under the same name, and in the European Union, Switzerland and Australia as Novothirteen.

Bleeding disorders are particularly amenable to treatment with recombinant blood clotting factors, and a number of products have recently reached market or are in late-stage development.

The FDA recently granted approval of Feiba (anti-inhibitor coagulant complex) by Baxter International Inc., of Deerfield, Ill., for routine prophylaxis to prevent or reduce frequency of bleeding episodes in patients with hemophilia A or B who have developed inhibitors.

And the agency gave the nod to an expanded indication for Kcentra (prothrombin complex concentrate [human]) from CSL Behring Ltd., of King of Prussia, Pa.

Kcentra previously was approved for urgent reversal of warfarin therapy in adults with acute major bleeding, and the new indication added urgent reversal of acquired coagulation factor deficiency induced by warfarin in adults needing an urgent surgery or other invasive procedure.

Baxter also submitted a biologics license application for OBI-1, a recombinant antihemophilic porcine sequence Factor VIII in patients with acquired hemophilia A. That submission was based on Phase II/III data showing that all patients in the trial experienced positive responses to treatment with OBI-1 within 24 hours of initiation of care. Baxter acquired that drug in January from Ipsen SA, of Paris, and Inspiration Biophparmaceuticals Inc., of Cambridge, Mass., in exchange for $50 million up front and up to $135 million in potential milestones, plus royalties. (See BioWorld Today, Jan. 15, 2013.)

At the same time, Daiichi Sankyo Co. Ltd., of Tokyo, submitted a supplemental new drug application for oral, once-daily direct Factor Xa inhibitor Lixiana (edoxaban tosilate hydrate) for Japanese approval of edoxaban in nonvalvular atrial fibrillation and symptomatic venous thromboembolism.

And at the December meeting of the American Society for Hematology (ASH), Biogen Idec Inc., of Cambridge, Mass., and Swedish Orphan Biovitrum AB, of Stockholm, presented an interim analysis of pediatric pharmacokinetics data showing that their long-lasting recombinant Factor IX and VIII Fc fusion protein candidates for hemophilia B and A, Alprolix and Eloctate, respectively, demonstrated that both have consistently prolonged half-lives in children vs. study participants’ prior therapies, which were consistent with pharmacokinetic results in adults and adolescents.

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