Inarigivir 25/50mg 12/24 周ACHIEVE实验结果

nevernevermind

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Data from the combined first two low dose inarigivir cohorts at weeks 12 and 24 with sequential Viread dosing demonstrate significant reductions in HBV DNA, HBV RNA and HBsAg
Data to be presented at the APASL 2018 Annual Meeting
HOPKINTON, Mass., March 14, 2018 (GLOBE NEWSWIRE) -- Spring Bank Pharmaceuticals, Inc. (SBPH) today announced that Nezam Afdhal, M.D., D.Sc., chief medical officer of Spring Bank, will make an oral presentation at the Asian Pacific Association for the Study of the Liver (APASL) 2018 Annual Meeting (March 14-18, 2018) in New Delhi, India.  The presentation will highlight combined results from both the 25 mg and 50 mg cohorts of Part A of the ongoing Phase 2 ACHIEVE trial examining the use of inarigivir soproxil for the treatment of chronic hepatitis B virus (HBV). Spring Bank is developing inarigivir, an orally-administered selective immunomodulator, as a potential backbone in a combinatorial treatment for HBV, with the goal of substantially increasing functional cure rates in a simple, safe and selective manner. All patients in the two low dose cohorts have completed sequential dosing of tenofovir disoproxil fumarate (marketed by Gilead Sciences, Inc. as Viread®) 300 mg daily for an additional 12 weeks.
“Data from the combined first two inarigivir monotherapy cohorts at weeks 12 and 24 demonstrate significant reductions in viral markers, including HBV DNA, HBV RNA and HBsAg, with a favorable safety and tolerability profile,” stated Dr. Afdhal.
The data presented at APASL includes 30 patients treated with inarigivir and 8 placebo patients from the first two low dose cohorts. Potent antiviral response, defined as > 1 log10 reduction in HBV DNA and > 3 log10 reduction (or to undetectable) in HBV RNA at the end of 12 weeks of inarigivir monotherapy treatment, was seen in 8 patients. Additionally, an enhanced anti-viral effect was observed in patients with baseline low viral burden, as measured by HBsAg (<104) and HBV DNA (<106). A dose relationship was observed between the pK and anti-viral efficacy at these initial low doses of inarigivir. Furthermore, the switch at week 12 to tenofovir disoproxil fumarate 300 mg was associated with significant reduction in HBV DNA but, as expected, showed little effect on further reductions in HBV RNA, potentially indicating the important dual mechanism of action of inarigivir as a direct acting anti-viral preventing HBV RNA encapsidation and an immuno-modulator stimulating immune-mediated clearance of cccDNA.
“When we examine the 11 HBeAg-negative patients who received inarigivir 25 mg or 50 mg monotherapy, we see a better response rate than in HBeAg-positive patients, with 55% of patients having a > 1 log10 reduction in HBV DNA and an associated > 3 log10 reduction in HBV RNA at the end of 12 weeks treatment. Additionally, 9 of the 30 (30%) patients had a > 0.5 log10 reduction in HBsAg at either week 12 or week 24 after transitioning to tenofovir disoproxil fumarate, a predictor of HBsAg loss with immune therapies such as interferon, highlighting the potential for inarigivir as a backbone treatment for HBV functional cure,” stated Dr. Afdhal.
Spring Bank also announced that it will soon complete the initial 12 weeks of patient dosing for the monotherapy treatment in the third cohort (100 mg) of Part A of the Phase 2 ACHIEVE trial. Subject to approval by the Data Safety Monitoring Board, Spring Bank anticipates starting recruitment of the fourth cohort (200 mg) in the first half of 2018.
As previously reported, Spring Bank has also entered into a clinical trial collaboration with Gilead Sciences, Inc., under which Gilead is funding and conducting a Phase 2 trial examining the co-administration of inarigivir and tenofovir alafenamide (marketed by Gilead as Vemlidy®) in patients with HBV. Similar to the protocol of Part B of the Spring Bank Phase 2 ACHIEVE trial, the protocol for this Phase 2 clinical trial involves 12 weeks concomitant administration of inarigivir (50 mg) and Vemlidy®. Following treatment, all patients will receive Vemlidy as a monotherapy for a further 36 weeks. Gilead recently initiated the inarigivir 50 mg + Vemlidy cohort of this clinical trial and it is expected that results from this study will be available in the second half of 2018.

nevernevermind

最新的结果，更详细的数据会在APASL2018 公布
新闻源为Yahoo.

StephenW

来自在第12周和第24周时连续Viread给药的组合的前两个低剂量inarigivir组的数据显示HBV DNA，HBV RNA和HBsAg显着减少
数据将在APASL 2018年会上提交
Spring Bank Pharmaceuticals，Inc.（SBPH）今天宣布，Spring Bank首席医疗官Nezam Afdhal医学博士将于2009年3月14日在马萨诸塞州剑桥市举行口头报告。亚太地区肝脏研究协会（APASL）2018年年会（2018年3月14 - 18日）在印度新德里举行。该演讲将突出显示来自正在进行的第二阶段ACHIEVE试验的A部分的25mg和50mg组群的结合的结果，该试验检查了使用奥沙瑞韦索普罗西治疗慢性乙型肝炎病毒（HBV）的情况。 Spring Bank正在开发口服给药选择性免疫调节剂 - inarigivir作为HBV联合治疗的潜在骨干，目标是以简单，安全和选择性的方式显着提高功能性治愈率。两个低剂量组群中的所有患者已经完成了连续12周的替诺福韦二吡呋酯富马酸盐（由Gilead Sciences，Inc。作为Viread？销售），每天300mg。
“Afdhal博士说：”在第12周和第24周结合的前两个inarigivir单药治疗组的数据显示病毒标志物显着减少，包括HBV DNA，HBV RNA和HBsAg，并具有良好的安全性和耐受性特征。
APASL提供的数据包括来自前两个低剂量队列的30名接受inarigivir治疗的患者和8名安慰剂患者。有效的抗病毒应答定义为HBV DNA减少> 1 log10，HBV RNA> 3 log10减少（或检测不到）。在8名患者中观察到inarigivir单药治疗12周结束时。另外，如通过HBsAg（<104）和HBV DNA（<106）所测量，在基线低病毒负荷的患者中观察到增强的抗病毒作用。在初始低剂量的inarigivir中观察到pK和抗病毒效力之间的剂量关系，在第12周时替换为替诺福韦二吡呋酯富马酸盐300mg与HBV DNA的显着减少相关，但是如预期的那样， HBV RNA的进一步降低，可能表明作为直接作用的抗病毒剂预防HBV RNA衣壳化的免疫调节剂刺激免疫介导的cccDNA的免疫调节剂的inarigivir的重要双重作用机制。
“当我们有11名HBeAg阴性患者接受单药治疗25mg或50mg单药治疗时，我们发现比HBeAg阳性患者有更好的缓解率，55％的患者HBV DNA降低> 1 log10，在12周治疗结束时HBV RNA降低≥3log10另外，30例（30％）患者中有9例在转换为替诺福韦酯替罗非昔酯富马酸盐后第12周或第24周的HBsAg降低> 0.5 log10预测HBsAg消失与干扰素等免疫疗法，突显了作为HBV功能治愈骨干治疗的潜在贫血患者，“Afdhal博士说。
春季银行还宣布，它将很快完成第二阶段ACHIEVE试验A部分第三队列（100 mg）单药治疗的最初12周患者用药。经数据安全监督委员会批准，Spring Bank预计将于2018年上半年开始招募第四批人群（200毫克）。
正如之前报道的，Spring Bank还与Gilead Sciences有限公司进行了临床试验合作，Gilead正在资助和开展第二阶段试验，审查共同施用inarigivir和替诺福韦alafenamide（由Gilead作为Vemlidy®销售）在HBV患者中。与Spring Bank Phase 2 ACHIEVE试验B部分的方案类似，本次2期临床试验研究的协议为12周，同时给予inarigivir（50 mg）和Vemlidy®。接受治疗后，所有患者Gilead最近都会接受该临床试验中的inarigivir 50 mg + Vemlidy队列的最近增加，预计该研究的结果将在2018年下半年提供。

nevernevermind

Dr. Afdhal 是SBPH的“首席药学官“
整个实验就我理解是12 wks Inarigivir (25/50 mg, 单药，低剂量）然后12 wks TDF （单药）
30人用药，8人安慰剂
有效抗病毒应答定义为：HBV DNA 减少> 1log, RNA > 3log 或检测不到
8个人达到应答。并且，增强的抗病毒效应在HBsAg < 4 log 且 DNA < 6 log 的低病毒负载病人中看到。（没看到他如何定义什么叫增强的抗病毒效应）。
HBeAg阴病人（11个）效果更好，55% 达到有效应答。
9个病人HBsAg 下降 > 0.5 log
100 mg将很快完成12wks实验。200 mg实验预期将在上半年招募病人
Gilead已经开始了(Inarigivir 50 mg + TAF) 12 wks + TAF 36 wks的实验，预计下半年有结果