候选疫苗显示慢性乙型肝炎患者的 HBsAg 持续降低

StephenW

候选疫苗显示慢性乙型肝炎患者的 HBsAg 持续降低
2022 年 11 月 8 日 • 凌晨 2:22 CST
通过 Halcyon Marine
（精准疫苗）

Vaccitech plc 昨天宣布更新其 HBV002 1/2 期临床试验的安全性和有效性数据的中期分析，该数据显示 VTP-300 可诱导慢性乙型肝炎 (HBV) 患者的 HBV 表面抗原 (HBsAg) 显着、持续降低.

HBsAg 是慢性 HBV 感染的标志。

在 VTP-300 给药后观察到针对所有编码抗原的强烈 T 细胞反应，特别是对于显着的 CD8+ T 细胞优势。

基线 HBsAg 较低的患者下降最为显着。

目前接受标准治疗 HBV 治疗的患者中，只有不到 10% 的患者实现了 HBsAg 持续下降或消失，这种状态与疾病的功能性治愈相关。

Vaccitech 首席科学官 Thomas Evans 医学博士在2022 年 11 月 7 日的新闻稿。

“我们在起始 HBsAg 水平较低的患者中观察到的显着效果支持正在进行的与 Arbutus Biopharma 的 siRNA AB-729 的合作研究，该研究已被证明可将大多数患者的 HBsAg 降低到 100 IU/mL 以下。”

“此外，我们相信因 VTP-300 导致 HBsAg 下降的患者可能会进一步受益于额外的 VTP-300 加强剂，我们正在另一项正在进行的研究中对其进行评估。”

第 2 组和第 3 组的患者也表现出对所有编码抗原的强烈 CD8+ T 细胞反应；核心蛋白、聚合酶和表面抗原。

截至 2022 年 9 月 28 日，VTP-300 作为单一疗法或与单次低剂量 nivolumab 联合给药，在加强剂量给药时没有与治疗相关的严重不良事件和罕见的短暂性转氨酶。

在 VTP-300 单药治疗组 2 (N=18) 中，5 名患者的基线 HBsAg 低于 100 IU/mL。在最后一剂 VTP-300 后五个月，这五名患者中的三名显示出 HBsAg 有意义且持久的降低，分别为 0.9、1.0 和 1.4 log10。

此外，在前一次给药后八个月，所有三名患者的这些减少都持续存在。

第 3 组 (N=18) 患者在加强剂量时接受了 VTP-300 与单次低剂量的纳武单抗联合治疗。 HBsAg 的平均 log10 降低在 3 个月时为 0.8（n=18），在 6 个月时为 0.9（n=10），在 9 个月时为 1.3（n=7），在基线 HBsAg 低于1,000 国际单位/毫升。

该组中有 5 名患者的基线 HBsAg 低于 100 IU/mL，其中 4 名患者的基线 HBsAg 下降超过 0.6 log10。

此外，2 名患者在 3 个月时出现无法检测到的 HBsAg，1 名患者在 6 个月和 9 个月时进行了评估，并继续保持未检测到的 HBsAg。

该公司确认 HBV002 试验的注册已经完成，最终更新预计在 2023 年第二季度初进行。

并且已经在亚太地区的多个国家启动了一项试验，以评估低剂量纳武利尤单抗和额外剂量的 VTP-300（HBV003；NCT05343481）的 MVA 增强成分的时机。

其他肝炎疫苗新闻发布在 PrecisionVaccinations.com/Hepatitis。
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员工审查

StephenW

Vaccine Candidate Shows Sustained Reductions of HBsAg in Chronic Hepatitis B Patients
November 8, 2022 • 2:22 am CST
by Halcyon Marine
(Precision Vaccinations)

Vaccitech plc announced yesterday an update to the interim analysis of safety and efficacy data from its HBV002 phase 1/2 clinical trial that shows VTP-300 induced meaningful, sustained reductions of HBV surface antigen (HBsAg) in people with chronic hepatitis B (HBV).

HBsAg is a hallmark of chronic HBV infection.

A robust T cell response against all encoded antigens was observed following VTP-300 administration, notably for marked CD8+ T cell predominance.

Declines were most prominent in patients with lower baseline HBsAg.

Fewer than 10% of patients on current standard-of-care HBV therapies achieve sustained HBsAg decrease or loss, a state associated with a functional cure of the disease.

"The updated interim data from this Phase 1b/2a study continues to support the potential of VTP-300 as a critical component of a functional cure for people with chronic hepatitis B," said Thomas Evans, M.D., Chief Scientific Officer of Vaccitech, in a press release on November 7, 2022.

"The prominent effect we are observing in patients with lower starting HBsAg levels supports the ongoing collaborative study with Arbutus Biopharma's siRNA, AB-729, which has been shown to reduce HBsAg below 100 IU/mL in a majority of patients."

"In addition, we believe patients experiencing declines in HBsAg due to VTP-300 could benefit further from additional VTP-300 boosters, which we are evaluating in an additional ongoing study."

Patients in Groups 2 and 3 also demonstrated a robust CD8+ T cell response against all encoded antigens; core protein, polymerase, and surface antigens.

VTP-300 was administered as a monotherapy or in combination with a single administration of low-dose nivolumab at the time of the booster dose was administered with no treatment-related serious adverse events and infrequent transient transaminitis as of September 28, 2022.

In the VTP-300 monotherapy Group 2 (N=18), five patients had baseline HBsAg under 100 IU/mL. Three of those five patients showed meaningful and durable reductions of HBsAg of 0.9, 1.0, and 1.4 log10, respectively, five months after the last dose of VTP-300.

Furthermore, these reductions persisted in all three patients at eight months after the previous dose.

Group 3 (N=18) patients received VTP-300 in combination with a single low dose of nivolumab at the time of the booster dose. The mean log10 reduction in HBsAg was 0.8 (n=18) at three months, 0.9 (n=10) at six months, and 1.3 (n=7) at nine months, with more prominent declines observed in patients with baseline HBsAg lower than 1,000 IU/mL.

Five patients in this group had baseline HBsAg lower than 100 IU/mL, of which four had declined over 0.6 log10.

Moreover, two patients developed non-detectable HBsAg at three months, and one was evaluated at 6 and 9 months and continued to maintain non-detectable HBsAg.

The company confirmed enrollment in the HBV002 trial is complete, with a final update expected early in the second quarter of 2023.

And a trial to evaluate the timing of low-dose nivolumab and additional doses of the MVA boost component of VTP-300 (HBV003; NCT05343481) has been initiated in multiple countries within the Asia-Pacific region.

Other hepatitis vaccine news is posted at PrecisionVaccinations.com/Hepatitis.
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Staff Review