Phase 3 Results of Bepirovirsen Treatment for Chronic Hepatitis B Virus Infection.

Methods

In two replicate, double-blindtrials (B-Well 1 and B-Well 2), we randomly assigned adults with noncirrhotic chronic HBV infection in a 2:1 ratio to receive subcutaneous bepirovirsen (at a weekly dose of 300 mg) or placebo for 24 weeks.

在两项复制的双盲试验（B-Well 1和B-Well 2）中，我们将非肝硬化慢性HBV感染的成人以2:1的比例随机分配接受皮下注射bepirovirsense（每周剂量为300毫克）或安慰剂，为期24周。

All the patients were receiving stable nucleoside or nucleotide analogue (NA) therapy and had an HBsAg level of more than 100 to 3000 IU per milliliter.

所有患者均接受稳定的核苷或核苷酸类似物（NA）治疗，并且HBsAg水平在每毫升100至3000国际单位之间。

Eligible patients discontinued NA therapy at 48 weeks.

符合条件的患者在48周时停止NA治疗。

The primary outcome was a functional cure at week 72.

主要结果是在第72周达到功能性治愈。

Results

The percentage of patients with a functional cure at week 72 was significantly higher with bepirovirsen than with placebo both in the B-Well 1 trial (in 127 of 650 patients [20%] vs. none of 328 patients) and in the B-Well 2 trial (in 106 of 570 patients [19%] vs. none of 286 patients).

在第72周，与安慰剂相比，使用bepirovirsen治疗的患者功能性治愈的百分比显著更高，无论是在B-Well 1试验中（650名患者中有127名[20%]，而328名患者中没有），还是在B-Well 2试验中（570名患者中有106名[19%]，而286名患者中没有）。

In a pooled analysis at 72 weeks, adverse events were reported in 91% of the patients in the bepirovirsen groups and in 73% of those in the placebo groups; serious adverse events were reported in 7% and 4% of the patients, respectively.

在72周的汇总分析中，贝匹罗韦森组有91%的患者和安慰剂组有73%的患者报告了不良事件；分别有7%和4%的患者报告了严重不良事件。

During the treatment period, adverse events of grade 3 or higher were reported in 16% of the patients who received bepirovirsen and in 3% of those who received placebo; increases in the alanine aminotransferase level were the most common grade 3 adverse events with bepirovirsen (in 6% of the patients).

在治疗期间，接受贝匹罗韦森治疗的患者中有16%和接受安慰剂治疗的患者中有3%报告了3级或更高级别的不良事件；贝匹罗韦森治疗中最常见的3级不良事件是丙氨酸氨基转移酶水平升高（占患者中的6%）。

Conclusions

In two phase 3 trials involving patients with chronic HBV infection, a functional cure after the discontinuation of NA therapy was reported in significantly more patients treated with bepirovirsen than in those who received placebo.

在涉及慢性乙型肝炎感染患者的两项III期试验中，与接受安慰剂的患者相比，接受贝匹罗韦森治疗后停用核苷类似物治疗的患者功能性治愈的报告显著更多。

(Funded by GSK; ClinicalTrials.gov numbers, NCT05630807 and NCT05630820.).

(由葛兰素史克资助；ClinicalTrials.gov编号，NCT05630807和NCT05630820。)