Final Analysis of a Study of Etranacogene Dezaparvovec for Hemophilia B.

Gene therapy offers the possibility of a single-dose treatment that produces durable endogenous factor IX expression and disease control.

基因治疗提供了单剂量治疗的可能性，可以产生持久的内源性凝血因子IX表达和疾病控制。

Etranacogene dezaparvovec comprises an adeno-associated virus serotype 5 (AAV5) vector and the highly active Padua factor IX variant.

Etranacogene dezaparvovec 包含一种腺相关病毒血清型 5 (AAV5) 载体和高度活跃的 Padua 因子 IX 变体。

The primary analysis of this study showed that etranacogene dezaparvovec reduced annualized bleeding rates and adverse events were mainly of low-grade severity.

本研究的主要分析显示，etranacogene dezaparvovec 降低了年化出血率，且不良事件主要是低级别的严重性。

Final data from 5 years of follow-up are now available.

现在可以获取5年随访的最终数据。

Methods

In this open-label, phase 3 study, after a lead-in period (≥6 months) of factor IX prophylaxis, we administered a single infusion of etranacogene dezaparvovec in men with hemophilia B (factor IX activity level, ≤2 IU per deciliter), regardless of preexisting AAV5 neutralizing antibodies.

在这项开放标签、第三阶段研究中，经过至少6个月的因子IX预防治疗的引入期后，我们向血友病B（因子IX活性水平≤2 IU/分升）的男性患者单次输注了etranacogene dezaparvovec，不论患者是否存在预先存在的AAV5中和抗体。

The prespecified 5-year analyses included adjusted annualized bleeding rates (difference between the post-treatment period of months 7 through 60 after gene therapy and the lead-in period), factor IX expression, and safety outcomes.

预先设定的5年分析包括调整后的年化出血率（基因治疗后第7个月至第60个月的治疗后期间与引入期之间的差异）、因子IX表达和安全性结果。

Results

In the full analysis population (54 participants), the adjusted annualized bleeding rate for all bleeding events was 4.16 during the lead-in period and 1.52 during months 7 through 60 after gene therapy, a reduction of 63% (95% confidence interval, 24 to 82).

在全部分析人群中（54名参与者），所有出血事件的调整年化出血率在引入期为4.16，基因治疗后第7个月至第60个月为1.52，减少了63%（95%置信区间，24至82）。

During the 5-year follow-up period, endogenous factor IX expression remained stable; at 5 years, the mean (±SD) factor IX activity level was 36.1±15.7 IU per deciliter and the mean exogenous factor IX consumption for routine prophylaxis and treatment of bleeding events had decreased by 96%, from 257,339 IU per year during the lead-in period to 10,924 IU per year during months 7 through 60 after gene therapy.

在5年的随访期间，内源性因子IX表达保持稳定；在5年时，平均（±标准差）因子IX活性水平为每分升36.1±15.7 IU，而用于常规预防和治疗出血事件的外源性因子IX消耗量从引导期的每年257,339 IU减少了96%，在基因治疗后的第7个月至第60个月期间每年为10,924 IU。

Efficacy did not differ substantially between participants with and those without AAV5 neutralizing antibodies at baseline.

基线时有无AAV5中和抗体的参与者之间的疗效没有显著差异。

Adverse events that were possibly related to treatment were rare after month 6.

治疗相关的不良事件在第6个月后非常罕见。

Conclusions

Sustained endogenous factor IX expression and low annualized bleeding rates over a 5-year period were observed after an infusion of etranacogene dezaparvovec.

在etranacogene dezaparvovec输注后，观察到内源性因子IX表达持续存在，且5年期间的年化出血率较低。

(Funded by uniQure and CSL Behring; HOPE-B ClinicalTrials.gov number, NCT03569891.).

(由uniQure和CSL Behring资助; HOPE-B临床试验注册号, NCT03569891。)