Objective:
This prospective clinical trial was conducted to assess the safety, efficacy and PK of BAX326 (a novel recombinant FIX [rFIX] manufactured without the addition of any materials of human or animal origin, and with two viral inactivation steps [solvent/detergent treatment and nanofiltration]) in previously-treated patients aged 12 to 65 with severe (FIX level < 1%) or moderately severe (FIX level ≤ 2%) hemophilia B.
Methods:
Hemostatic efficacy after twice weekly prophylaxis with BAX326 was determined in terms of annualized bleeding rate (ABR) compared with a historical control group treated on- demand. PK equivalence was assessed between BAX326 and a commercial rFIX in a crossover design. Safety was evaluated by the occurrence of adverse events.
Summary:
In subjects on twice weekly prophylaxis with BAX326 over at least 3 months (N=56), 24 (43%) did not bleed throughout the study observation period, and the ABR was substantially lower when compared with a historical control group (79% reduction, p<0.001). Joint bleeds (major joints: wrist, elbow, shoulder, hip, knee, ankle) occurred at a mean ABR of 2.85 ± 4.25 compared with 1.41 ± 2.87 in non-joint bleed sites. Of the 32/56 subjects with bleeds, 90.6% (29/32) had arthropathy at screening and only 28.1% (9/32) did not have target joints, as compared to subjects without bleeds, of whom 79.2% (19/24) had arthropathy and 50% (12/24) did not have target joints at screening. Higher mean ABRs were observed in subjects with arthropathy (N=46) versus without arthropathy (N=8) (4.54 vs. 2.57 for all bleeds, 3.16 vs. 1.02 for joint bleeds, and 1.97 vs. 0.25 for spontaneous bleeds). A similar pattern was observed for the ABRs of joint bleeds and spontaneous bleeds in subjects with target joints (N=35) (mean ABR: 2.41 ± 3.79) and those with no target joints (N=21) (mean ABR: 0.58 ± 1.63). Most bleeds were controlled with 1-2 infusions of BAX326 and with an efficacy rating of “excellent.” BAX326 was equivalent to the comparator rFIX in terms of AUC 0 72 h /dose. BAX326 is safe and well tolerated in hemophilia B patients, with no signs of immunogenicity or thrombotic events.
Conclusions:
BAX326 has a positive safety profile and is efficacious in treating bleeds and in routine prophylaxis in PTPs aged ≥12 years with hemophilia B. The results also demonstrate that subjects with target joints and hemophilic arthropathy receiving secondary prophylaxis tend to have higher ABRs as compared to those without these underlying conditions.