强生，葛兰素史克（GSK）和Vir / Alnylam提供了乙肝治疗候选药

StephenW

J&J, GSK, and Vir/Alnylam present positive data for hepatitis B treatment candidates, but hopes for a cure remain muted
GlobalData Healthcare
9th September 2020 (Last Updated September 9th, 2020 15:16)
At the Digital International Liver Congress that took place in the last week of August, Johnson & Johnson, GlaxoSmithKline, and Vir Biotechnology/Alnylam presented positive data from clinical studies of their hepatitis B drugs. All companies are on a quest to find a functional cure for chronic hepatitis B infections (CHB), which affect more than 250 million people worldwide and can lead to liver failure and liver cancer, with a large number of these cases being in China and Brazil. Conventional nucleos(t)ide analogue treatment (NA), such as tenofovir disoproxil fumarate (TDF) or entecavir, can reduce the hepatitis B viral load, measured as surface antigen HBsAg, which is a marker of chronic hepatitis B virus (HBV) infections, but it cannot eliminate the virus from human hepatocytes. Promising new data are emerging; however, they are from small trials, and it is unclear if any of these agents may represent a cure for this chronic condition.

J&J’s subsidiary Janssen Pharmaceuticals and Arrowhead’s RNA interference (RNAi) therapy JNJ-3989 reduced HBsAg for up to 48 weeks after only three doses when given in combination with conventional NA treatment. In the Phase II trial with 38 participants, three doses of JNJ-3989 were given 28 days apart and participants were observed for up to 50 weeks. In 15 patients, HBsAg levels declined by more than 2 log10 IU/mL on average and stayed at a low level until the end of the observation period. The researchers said these data showed HBsAg reductions for an extended period of time for the first time.

GSK also presented positive data from a Phase IIa trial with 31 patients of its investigational antisense oligonucleotide GSK’836 (GSK3228836), showing that the drug significantly reduced HBsAg on average by 1.56 log10 IU/mL after four weeks of treatment in an NA-naïve group with 12 patients.

Vir Technology partnered with RNAi specialist Alnylam to develop VIR-2218, which is designed to silence all HBV transcripts from both closed circular DNA (cccDNA) and integrated DNA across all 10 HBV genotypes. In the ongoing Phase II study, 24 patients who received a 50mg dose of the drug showed a maximal decline in HBsAg levels after 12 weeks with a mean decline of 1.5 log10 IU/mL from baseline.

After a functional cure was found for hepatitis C with Gilead’s Sovaldi and Harvoni, pharma companies are now trying to develop antivirals that can eliminate HBV infections. However, the two viruses have some significant differences; HCV is an RNA virus and HBV is a DNA virus, and HBV forms covalent cccDNA in human cells that are stable and to date cannot be targeted by drugs. The new data from GSK, J&J, and Vir/Alnylam are promising and now long-term studies must show the duration of the viral reduction and which parameters affected patient responses to each therapeutic.

StephenW

强生，葛兰素史克（GSK）和Vir / Alnylam提供了乙肝治疗候选药物的阳性数据，但治愈的希望依然渺茫
GlobalData医疗保健
2020年9月9日（最后更新时间：2020年9月9日15:16）
在8月最后一周举行的数字国际肝脏大会上，强生（Johnson＆Johnson），葛兰素史克（GlaxoSmithKline）和Vir Biotechnology / Alnylam提供了来自其乙肝药物临床研究的积极数据。所有公司都在寻找一种能够治愈慢性乙型肝炎（CHB）的功能性疗法，该病在全球影响着超过2.5亿人，并可能导致肝衰竭和肝癌，其中许多病例在中国和巴西。常规的核苷酸类似物治疗（NA），例如替诺福韦富马酸二甲氧吡啶（TDF）或恩替卡韦，可以降低乙型肝炎病毒载量，以表面抗原HBsAg衡量，它是慢性乙型肝炎病毒（HBV）感染的标志，但是它无法从人肝细胞中清除病毒。有希望的新数据正在涌现；但是，这些药物来自小型试验，目前尚不清楚这些药物是否可以代表这种慢性病的治愈方法。

强生的子公司Janssen Pharmaceuticals和Arrowhead的RNA干扰（RNAi）治疗JNJ-3989与常规NA治疗联合使用仅三剂后，最多可以减少HBsAg长达48周。在有38名参与者的II期试验中，三剂JNJ-3989的间隔时间为28天，并观察了长达50周的参与者。在15例患者中，HBsAg水平平均下降超过2 log10 IU / mL，并一直保持较低水平，直到观察期结束。研究人员说，这些数据表明，HBsAg首次减少了很长时间。

GSK还提供了来自IIa期临床试验的31位患者的反义寡核苷酸GSK'836（GSK3228836）的阳性数据，表明该药物在NA初始治疗中治疗4周后，HBsAg平均平均降低HBsAg 1.56 log10 IU / mL。本组12例。

Vir Technology与RNAi专家Alnylam合作开发了VIR-2218，该产品旨在使来自所有10种HBV基因型的闭合环状DNA（cccDNA）和整合DNA的所有HBV转录子沉默。在正在进行的II期研究中，接受50mg剂量药物的24名患者在12周后显示HBsAg水平最大下降，平均较基线下降1.5 log10 IU / mL。

在通过吉利德（Gilead）的Sovaldi和Harvoni发现了丙型肝炎的功能性治愈后，制药公司现在正在尝试开发可以消除HBV感染的抗病毒药。但是，这两种病毒有一些显着差异。 HCV是一种RNA病毒，而HBV是一种DNA病毒，并且HBV在人细胞中形成稳定的共价cccDNA，并且迄今为止尚不能被药物靶向。来自GSK，J＆J和Vir / Alnylam的新数据很有希望，现在的长期研究必须显示病毒减少的持续时间以及哪些参数影响患者对每种疗法的反应。

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