Eloctate Gets FDA Nod for Patients With Hemophilia A
First hemophilia A therapy to extend interval between prophylactic infusions
The FDA has approved Eloctate, antihemophilic factor (recombinant), Fc fusion protein (Biogen Idec, Inc.), for use in adults and children with hemophilia A.
Eloctate is the first hemophilia A treatment designed to require less frequent injections when used to prevent or reduce the frequency of bleeding. The product received an “orphan drug” designation from the FDA because it is intended for the treatment of a rare disease or condition.
Eloctate is approved to help control and prevent bleeding episodes, to manage bleeding during surgical procedures, and to prevent or reduce the frequency of bleeding episodes (prophylaxis). The product consists of the coagulation factor VIII molecule (also known as antihemophilic factor) linked to a protein fragment, Fc, which is found in antibodies. This makes the product last longer in the patient’s blood.
The recommended starting prophylactic regimen for Eloctate is 50 IU/kg every 4 days. Based on the patient’s clinical response, the regimen may be adjusted in the range of 25 to 65 IU/kg and every 3 to 5 days.
The FDA’s approval was based on results from the global phase III A-LONG trial as well as on interim pharmacokinetic and safety data from the phase III Kids A-LONG study.
The A-LONG trial was an open-label study that examined the efficacy, safety, and pharmacokinetics of Eloctate in 165 previously treated male subjects 12 years of age and older with severe hemophilia A. The results showed that adults and adolescents with severe hemophilia A achieved a statistically significant reduction of bleeding episodes in both of the study’s prophylaxis arms compared with the on-demand treatment arm. In addition, 98% of bleeding episodes were controlled with one or two infusions of Eloctate.
The study evaluated individualized and weekly prophylaxis to reduce or prevent bleeding episodes as well as on-demand dosing to treat bleeding episodes. In the individualized-treatment arm, each study participant started on a twice-weekly dosing regimen. Participants’ pharmacokinetic parameters were used to guide adjustments to the dosing interval (every 3 to 5 days) and dose (25 to 65 IU/kg) to target a minimum factor VIII level of 1 to 3 IU/dL or higher, as needed, to maintain control of breakthrough bleeding episodes. In the study, the dose in the weekly prophylaxis arm was 65 IU/ kg/week. The overall median annualized bleeding rates (i.e., the projected number of bleeding episodes per year) reported in the study were 1.6 for the individualized prophylaxis arm, 3.6 for the weekly prophylaxis arm, and 33.6 for the on-demand arm.
The pediatric indication for Eloctate is supported by interim safety and pharmacokinetic results in 38 boys 2 to 11 years old from the phase III Kids A-LONG study. These data showed that Eloctate was generally well-tolerated, and no inhibitors were detected. The relative increase in half-life seen with Eloctate was consistent with findings in adults and adolescents. In comparison with adults and adolescents, children 2 to 5 years old have a shorter half-life and higher clearance of hemophilic factors (adjusted for body weight); therefore, a higher dose or more frequent dosing may be needed in this age group.
Hemophilia A is an inherited, sex-linked, blood-clotting disorder that primarily affects males. It is caused by defects in the factor VIII gene. Hemophilia A affects 1 in every 5,000 males born in the U.S. Individuals with hemophilia A may experience repeated episodes of serious bleeding, mainly into the joints, which can be severely damaged by the bleeding.Eloctate is expected to be launched in the U.S. in July 2014.