FDA Approves New Indication for Kogenate FS in Adults With Hemophilia A
Significantly fewer bleeds with prophylaxis than with on-demand treatment
The FDA has approved a new indication for Kogenate FS (antihemophilic factor VIII [recombinant], Bayer) for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults with hemophilia A.
The approval was based on data from the phase III SPINART (Secondary Prophylaxis IN Adults, a Randomized Trial) study, in which 84 subjects were randomly assigned to receive Kogenate FS either as prophylaxis (25 IU/kg three times per week) or as on-demand therapy.
The new findings were published in the Journal of Thrombosis and Haemostasis.
In the study, patients were stratified based on target joints (present vs. absent) and on the number of bleeding events during the previous 6 months (≥ 15 vs. < 15 annualized bleeds). Safety and efficacy results from an analysis of the primary endpoint of bleeding frequency after a median follow-up period of 1.4 years provided the basis for the FDA’s approval. The study’s safety objectives were also met.
The SPINART trial was an open-label, randomized, parallel-group study of 84 male subjects aged 15 to 50 years with severe hemophilia A (< 1% FVIII:C). In this phase III trial, the subjects were randomly assigned to receive Kogenate FS either as a prophylaxis regimen of 25 IU/kg three times per week (n = 42) or as on-demand therapy (n = 42). Escalation by 5-IU/kg increments (to a maximum of 30 or 35 IU/kg) was allowed in subjects with 12 or more annual bleeds after 1 and 2 years of treatment. The study’s primary endpoint was the frequency of bleeding after all patients had completed at least 1 year of therapy.
Patients who received prophylaxis experienced significantly fewer bleeds (P < 0.0001) compared with patients treated on-demand, regardless of the baseline subgroups examined (e.g., age, bleeding history, and presence or absence of target joints). The ratio of the mean bleeding frequency was 15.2 (P < 0.0001) for on-demand treatment versus prophylaxis, indicating that patients who received on-demand treatment experienced, on average, 15.2 times as many bleeds compared with patients receiving prophylaxis.
The mean annualized bleeding rates (bleeds/subject/year) were 37 in the on-demand group compared with two in the prophylaxis group. The median annualized bleeding rate (bleeds/subject/year) in the on-demand group was 33 versus 0 in the prophylaxis group. Of the 42 prophylaxis subjects, 22 (52%) experienced no bleeding and 12 (29%) experienced one or two bleeds during the follow-up period.
Serious adverse reactions with Kogenate FS included systemic hypersensitivity reactions (e.g., bronchospastic reactions and/or hypotension and anaphylaxis), and the development of high-titer inhibitors necessitating the use of alternatives to factor VIII. The most common adverse reactions observed in clinical trials of Kogenate FS were inhibitor formation in previously untreated and minimally treated patients; skin-related hypersensitivity reactions (e.g., rash and pruritus); infusion-site reactions (e.g., inflammation and pain); and central venous access device (CVAD)-associated infections.
Kogenate FS (antihemophilic factor [recombinant]) is a medication used to replace clotting factor (factor VIII or antihemophilic factor) that is missing in people with hemophilia A. The product is used to prevent or control bleeding in adults and children with hemophilia A. It is not used to treat von Willebrand disease.
Hemophilia A, also known as factor VIII deficiency or classic hemophilia, is a largely inherited bleeding disorder in which one of the proteins needed to form blood clots is missing or reduced. Hemophilia A is the most common type of hemophilia and is characterized by prolonged or spontaneous bleeding, especially into the joints, muscles, or internal organs.
Source: PR Newswire; May 12, 2014.