葛兰素史克乙肝治疗的疗效在第 2 阶段的完整读数中下降了 6

StephenW

葛兰素史克乙肝治疗的疗效在第 2 阶段的完整读数中下降了 60%，但第 3 阶段继续进行
詹姆斯·沃尔德伦
2022 年 11 月 8 日上午 11:37
GSK慢性乙型肝炎
葛兰素史克
该公司指出，基线乙型肝炎表面抗原水平低的患者是一个潜在的亚组，他们将从治疗中受益最多。 (葛兰素史克)

GSK 治疗乙型肝炎的疗效在中期分析和研究结束分析之间可能下降了 60% 以上，但大型制药公司仍然希望反义寡核苷酸治疗能够为感染提供功能性治疗。

B-Clear 2b 期试验的研究结束结果显示，9% 的慢性乙型肝炎患者接受稳定的核苷/核苷酸类似物 (NA) 治疗，10% 的未接受 NA 治疗的患者实现了研究的主要结果：持续清除其乙型肝炎表面抗原水平和乙型肝炎病毒 (HBV) DNA 水平。患者接受了 24 周的每周 300 毫克剂量的治疗。

今天在美国肝病研究协会会议上公布的读数是继 6 月以来关于贝匹罗韦森的更令人印象深刻的初步数据，该数据显示 28% 至 29% 的参与者在 24 周后检测不到病毒水平。虽然葛兰素史克在一封电子邮件中告诉 Fierce Biotech，“正如预期的那样”，一些参与者在治疗结束后复发了，这意味着他们的感染已经增加到可检测的水平，但目前尚不完全清楚是什么导致了两次读数之间的这种差距。

葛兰素史克在他们的电子邮件中指出，即使是 10% 的患者有效率，也比目前的护理标准高出约 10 倍。

该公司还指出了一个数据表明将从治疗中受益最大的亚组。在基线乙型肝炎表面抗原水平较低的患者中，16% 的同时服用 NA 的患者看到了可检测水平的病毒清除，25% 的未服用 NA 的患者实现了这一目标。
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乙肝主要玩家吉利德和 Vir 联手寻找治愈方法

B-Sure 试验将研究长期反应的持久性，该试验将额外跟踪参与者 33 个月，并研究通过停止其他治疗，贝匹罗韦森是否可以证明是乙肝患者的功能性治愈。

“今天 B-Clear 研究的结果对于大约 3 亿慢性乙型肝炎患者来说是向前迈出的有希望的一步，”葛兰素史克开发高级副总裁 Chris Corsico 在 11 月 8 日的新闻稿中说。 “我们期待从明年开始在我们的第 3 期研究中确认贝匹罗韦森的这些发现，并探索潜在的序贯治疗方案，以帮助更多患有 [慢性乙型肝炎] 的人实现功能性治愈。”

目前，乙型肝炎治疗工具包以干扰素类分子和 NAs 为中心，如恩替卡韦、富马酸替诺福韦酯和替诺福韦艾拉酚胺。干扰素分子可以增强免疫系统，而 NA 会阻止或减缓病毒的复制。然而，即使联合使用，也只有一小部分患者的乙型肝炎表面抗原水平无法检测——这就是所谓的功能性治愈。

GSK 已于 2019 年向 Ionis Pharmaceuticals 支付了 2500 万美元用于其乙型肝炎项目，该公司是试图提高无法检测到抗原水平的患者比例的公司之一。该公司今天表示，它计划明年启动贝匹罗韦森的 3 期试验，同时正在进行的 2 期试验以探索潜在的序贯治疗方案。

StephenW

GSK hep B treatment’s efficacy slips 60% in full phase 2 readout, but phase 3 going ahead
By James Waldron
Nov 8, 2022 11:37am
GSKchronic hepatitis B
GSK
The company pointed to patients with low baseline hepatitis B surface antigen levels as a potential subgroup who would benefit most from the treatment. (GSK)

The efficacy of GSK's hepatitis B treatment may have dropped by over 60% between the interim and end-of-study analysis, but the Big Pharma is still hopeful the antisense oligonucleotide treatment will provide a functional cure for the infection.

The end-of-study results from the B-Clear phase 2b trial showed that 9% of patients with chronic hepatitis B on stable nucleoside/nucleotide analogues (NA) treatment and 10% of those not on NA treatment achieved the study’s primary outcome of a sustained clearance of their hepatitis B surface antigen levels and hepatitis B virus (HBV) DNA levels. Patients received 24 weeks of treatment with a 300 mg weekly dose.

Today’s readout, presented at the American Association for the Study of Liver Diseases’ Meeting, follows far more impressive initial data on bepirovirsen from June, which showed that 28 to 29% of participants had undetectable levels of the virus after 24 weeks. It’s not entirely clear what led to such a gap between the two readouts, although GSK told Fierce Biotech in an email that “as expected” some participants relapsed after the end of treatment, meaning their infection had since increased to detectable levels.

And even a 10% effectiveness rate among patients is around tenfold higher than the current standard of care, GSK pointed out in their email.

The company also pointed to a subgroup who the data suggests would benefit most from the treatment. Of patients with low baseline hepatitis B surface antigen levels, 16% who were also taking NAs saw a clearance of detectable levels of the virus and 25% of those not on NAs achieved this.
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Major hep B players Gilead and Vir join forces to find a cure

Longer term durability of response will be investigated in the B-Sure trial, which will follow participants for an additional 33 months and investigate whether by stopping other treatments bepirovirsen can be shown to be a functional cure in hep B patients.

“Today’s results from the B-Clear study are a promising step forward for the approximately 300 million people living with chronic hepatitis B,” Chris Corsico, SVP of Development at GSK, said in a Nov. 8 release. “We look forward to confirming these findings for bepirovirsen in our phase 3 study starting next year, as well as exploring potential sequential therapy options with the aim of helping more people living with [chronic hepatitis B] achieve functional cure.”

Currently, the hepatitis B treatment toolkit centers on interferon-type molecules and NAs such as entecavir, tenofovir disoproxil fumarate and tenofovir alafenamide. Interferon molecules boost the immune system, and NAs stop or slow replication of the virus. Yet, even when used in combination, only a small percentage of patients have undetectable levels of hepatitis B surface antigen—what is known as achieving functional cure.

GSK, having paid Ionis Pharmaceuticals $25 million upfront in 2019 for its hepatitis B program, is one of a set of companies trying to ramp up the percentage of patients with undetectable levels of the antigen. The company said today that it plans to launch a phase 3 trial for bepirovirsen next year, alongside ongoing phase 2 trials to explore potential sequential treatment options.