Lambert T, Recht M, Valentino L A, Powell J S, Udata C, Sullivan S T, Roth D A
Centre de Traitement des Hémophiles, Hôpital de Bicêtre AP-HP, Le Kremlin Bicêtre, France.
Haemophilia. 2007 May;13(3):233-43. doi: 10.1111/j.1365-2516.2007.01458.x.
BeneFix, the only recombinant factor IX (FIX), has been reformulated. The reformulation involves a change in diluent and allows for more concentrated infusions of recombinant FIX. A double-blind, randomized, pharmacokinetic (PK) crossover study demonstrated that reformulated BeneFix was bioequivalent to original BeneFix and follow-up PK evaluation after 6 months of treatment demonstrated the PK stability of reformulated BeneFix after multiple exposures. Favourable efficacy and safety profiles, consistent with those already well-established for original BeneFix, were observed: 81.1% of haemorrhages resolved with only a single infusion; 85.3% of initial treatment response ratings were Excellent or Good; more than half of the subjects using reformulated BeneFix for routine prophylaxis (11 of 17, 64.7%) had no spontaneous haemorrhages during their 6-12 month course of prophylactic treatment, with an overall spontaneous bleeding rate of 0.72 year(-1); and for the single surgical procedure (knee washing), treatment was rated Useful. In addition, there was no FIX inhibitor development, allergic-type manifestations, or thrombogenic complications with more than 1100 infusions (nearly 5.2 million IUs) administered in this trial. All efficacy and safety outcomes from this study were achieved with more concentrated recombinant protein infusions than that possible with original BeneFix, and utilization of the 2000 IU per vial dosage strength, newly introduced with the reformulated product, was high (>62%). The reformulation of BeneFix allows smaller delivery volumes and an increased choice of dosage strengths without altering the PK properties (including incremental recovery and half-life) or the established efficacy and safety profile of recombinant FIX.
唯重组凝血因子IX产品BeneFix已重新配方。重新配方涉及稀释剂的改变，并允许更浓缩地输注重组凝血因子IX。一项双盲、随机、药代动力学（PK）交叉研究表明，重新配方的BeneFix与原BeneFix具有生物等效性，并且在治疗6个月后的后续PK评估显示，多次输注后重新配方的BeneFix具有PK稳定性。观察到了与原BeneFix已确立的良好疗效和安全性特征相符的情况：81.1%的出血仅通过单次输注即可解决；85.3%的初始治疗反应评级为优秀或良好；在接受重新配方的BeneFix进行常规预防的受试者中，超过一半（17名中的11名，64.7%）在其6至12个月的预防治疗过程中没有自发性出血，总体自发性出血率为0.72次/年；对于单次外科手术（膝关节冲洗），治疗被评为有效。此外，在该试验中进行了超过1100次输注（近520万国际单位），未出现凝血因子IX抑制剂产生、过敏样表现或血栓形成并发症。本研究的所有疗效和安全性结果都是通过比原BeneFix更浓缩的重组蛋白输注实现的，并且新推出的重新配方产品每瓶2000国际单位剂量规格的使用率很高（>62%）。BeneFix的重新配方允许更小的给药体积和更多的剂量规格选择，而不会改变PK特性（包括增量回收率和半衰期）或重组凝血因子IX已确立的疗效和安全性特征。
