Treatment of Congenital Fibrinogen Deficiency; Global Development Plan for a Double Virus Inactivated Fibrinogen Concentrate

Abstract 4636

Congenital afibrinogenaemia and hypofibrinogenaemia are rare inherited disorders occurring in homozygotic patients with an estimated incidence of 1 in 10⁶. Patients present with frequent severe bleeding episodes since birth or early childhood. Bleeding may occur after a minor trauma or a small surgical intervention, into the skin, mucosa, muscles, gastrointestinal tract, or the brain. Therapeutic substitution with human fibrinogen concentrate can correct the haemostatic defect and arrest the bleeding in patients with these fibrinogen deficiencies. Octafibrin is a highly purified, lyophilized, human plasma fibrinogen concentrate, without added albumin. Octafibrin is double virus inactivated using 2 dedicated virus inactivation/removal steps, solvent/detergent treatment, and nanofiltration. A plan for the global development of Octafibrin has been prepared taking into account discussions with European Regulators and the FDA. This plan also involves discussions with the European pediatric committee (PDCO) which oversees the inclusion of pediatric subjects into drug development under the new EMA guidelines.

The development plan calls for a prospective, randomized, open label, multinational, pivotal PK comparison of Octafibrin to an existing marketed product in 18 adult and adolescent patients, including comparison of a surrogate efficacy endpoint measured by TEG. In a second study the efficacy and safety of the product in bleeding and invasive procedures will be assessed in 24 adult and adolescent patients. Finally a pediatric PK, efficacy and safety study in patients below 6 years will be performed but because of the rarity of these patients this study will not need to be completed before review and approval by the regulatory agencies. Clinical studies are planned to be started later this year.

A double virus inactivated, plasma derived fibrinogen concentrate (Octafibrin) will be globally developed in an ultra rare congenital disease after harmonized discussions with EU and US regulators. Pivotal comparative PK data and interim efficacy and safety data will be available at time of regulatory submissions while the finalization of the pediatric study is deferred.

Effective management of congenital fibrinogen deficiencies in bleeding situations is necessary for the prevention of potentially life-threatening bleeding episodes. This clinical program will help to confirm that fibrinogen substitution is able to successfully control bleeding, increase the fibrinogen plasma levels, and reduce the amount of transfusions needed with allogeneic blood products. In addition, it will give additional information on the tolerability and overall safety profile of fibrinogen replacement therapy.