肝胆相照论坛

标题: 好消息！ARO-HBV开始三联用药临床试验 [打印本页]

作者: sir 时间: 2019-4-24 22:56 标题: 好消息！ARO-HBV开始三联用药临床试验

Arrowhead今天宣布开始ARO-HBV队列12的三联用药临床试验，具体的联合使用药物的方案由强生制定，目前还没有公布具体信息，三联方案估计是核苷+ARO-HBV+干扰素（或者是强生的处于二期的衣壳抑制剂也有可能），RNAi到底能不能实现功能性治愈就看三联方案的结果了。

作者: fuke 时间: 2019-4-24 23:01

三联用药应该是之前的两个联合加干扰素，核衣壳应该不会。

作者: newchinabok 时间: 2019-4-24 23:01

sir 发表于 2019-4-24 22:56
Arrowhead今天宣布开始ARO-HBV队列12的三联用药临床试验，具体的联合使用药物的方案由强生制定，目前还没有 ...

消息源有链接吗？

作者: sir 时间: 2019-4-24 23:09

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arrowhead官网

作者: newchinabok 时间: 2019-4-24 23:09

sir 发表于 2019-4-24 23:09
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arrowhead官网

查了没看见

作者: sir 时间: 2019-4-24 23:12

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investor-press release

作者: newchinabok 时间: 2019-4-24 23:14

sir 发表于 2019-4-24 23:12
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investor-press release

也查了，能不能复制一点文字

作者: newchinabok 时间: 2019-4-24 23:17

查遍了，没看见？

作者: sir 时间: 2019-4-24 23:17

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Arrowhead Begins Triple Combination Cohort in Chronic HBV Patients and Earns $25 Million
Milestone Payment from Janssen
April 24, 2019
PASADENA, Calif.--(BUSINESS WIRE)--Apr. 24, 2019-- Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today announced that it has begun
dosing in a new triple combination cohort (cohort 12) that includes JNJ-3989 (formerly ARO-HBV) and additional undisclosed agents selected by
Janssen Pharmaceuticals, Inc. in its ongoing Phase 1/2 study (AROHBV1001) in patients with chronic hepatitis B virus (HBV). In connection with the
start of this new cohort, Arrowhead has earned a $25 million milestone payment from Janssen Pharmaceuticals, Inc., part of the Janssen
Pharmaceutical Companies of Johnson & Johnson.
Christopher Anzalone, Ph.D., president and chief executive officer at Arrowhead, said: “Both Arrowhead and Janssen share the aim to advance
transformational medicines that achieve higher rates of functional cure with a finite treatment duration for patients with chronic hepatitis B viral
infection. Beginning this new triple combination cohort in our ongoing AROHBV1001 study has the potential to generate valuable data rapidly.”
AROHBV1001 (NCT03365947) is a Phase 1/2 clinical study evaluating the safety, tolerability, and pharmacokinetic effects of single-ascending doses
(SAD) of ARO-HBV in healthy adult volunteers, as well as the safety, tolerability, and pharmacodynamic effects of multiple-ascending doses (MAD) of
ARO-HBV in patients with chronic HBV.
Arrowhead entered into a license and collaboration agreement with Janssen in October 2018 to develop and commercialize ARO-HBV. Under the
initial terms of the HBV license agreement, Arrowhead was eligible to receive a $50 million milestone payment linked to a Phase 2 study. Arrowhead
and Janssen subsequently amended the HBV license agreement to accelerate the payment of $25 million of the $50 million Phase 2 milestone with
the initiation of cohort 12 of the AROHBV1001 trial. Arrowhead is eligible to receive the remaining $25 million upon the initiation of a Phase 2 study by
Janssen.
Hepatitis B

作者: sir 时间: 2019-4-24 23:19

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Arrowhead在慢性HBV患者中开始了三重组合队列，收入2500万美元。

Janssen的里程碑付款

2019年4月24日

加利福尼亚州帕萨迪纳——（商业电报）——2019年4月24日——箭头制药公司（Nasdaq:ARWR）今天宣布，该公司已经开始

在一个新的三重组合队列（队列12）中给药，包括JNJ-3989（以前的ARO-HBV）和其他未公开的药物，这些药物由

Janssen Pharmaceuticals，Inc.正在对慢性乙型肝炎病毒（HBV）患者进行1/2阶段研究（arohbv1001）。关于

从这个新的团队开始，Arrowhead已经从Janssen制药公司（Janssen Pharmaceuticals，Inc.）获得了2500万美元的里程碑式付款。

强生制药公司。

箭头公司总裁兼首席执行官克里斯托弗·安佐尼博士说：“箭头公司和詹森公司都有共同的前进目标。

慢性乙型肝炎病毒患者在有限治疗时间内获得更高功能治愈率的转化药物

感染。在我们正在进行的arohbv1001研究中，开始这个新的三重组合队列具有快速生成有价值数据的潜力。”

arohbv1001（NCT03365947）是一项1/2阶段临床研究，评估单次递增剂量的安全性、耐受性和药代动力学效应。

健康成人志愿者ARO-HBV（SAD）及多剂量递增（MAD）对ARO-HBV的安全性、耐受性和药效学影响。

慢性乙型肝炎患者的ARO-HBV。

Arrowhead于2018年10月与Janssen签订了一份许可和合作协议，以开发和商业化ARO-HBV。下

根据HBV许可协议的初始条款，Arrowhead有资格获得与第2阶段研究相关的5000万美元里程碑付款。箭头

Janssen随后修订了HBV许可协议，以加速支付5000万美元的第二阶段里程碑的2500万美元。

arohbv1001试验第12队列的开始。在Janssen进行的第二阶段研究开始后，Arrowhead有资格获得剩余的2500万美元

作者: newchinabok 时间: 2019-4-24 23:27

sir 发表于 2019-4-24 23:19
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Arrowhead在慢性HBV患者中开始了三重组合队列，收入2500万美元。

感谢分享

新的三组联合队列(队列12)，包括JNJ-3989(以前是ARO-HBV)和其他未公开的药物

作者: 乙肝人1949 时间: 2019-4-24 23:28

持续跟进

作者: Fater 时间: 2019-4-24 23:30

巨大的好消息！期待！

作者: rxsm 时间: 2019-4-24 23:31

该出手就出手啊……

作者: hchu 时间: 2019-4-25 07:50

“慢性乙型肝炎病毒患者在有限治疗时间内获得更高功能治愈率的转化药物。”

收下了。谢谢！

作者: 齐欢畅 时间: 2019-4-25 08:24

Arrowhead Begins Triple Combination Cohort in Chronic HBV Patients and Earns $25 Million Milestone Payment from Janssen
Apr 24, 2019 at 7:30 AM EDT
PASADENA, Calif. --(BUSINESS WIRE)--Apr. 24, 2019-- Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today announced that it has begun dosing in a new triple combination cohort (cohort 12) that includes JNJ-3989 (formerly ARO-HBV) and additional undisclosed agents selected by Janssen Pharmaceuticals,
PDF Version
PASADENA, Calif.--(BUSINESS WIRE)--Apr. 24, 2019-- Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today announced that it has begun dosing in a new triple combination cohort (cohort 12) that includes JNJ-3989 (formerly ARO-HBV) and additional undisclosed agents selected by Janssen Pharmaceuticals, Inc. in its ongoing Phase 1/2 study (AROHBV1001) in patients with chronic hepatitis B virus (HBV). In connection with the start of this new cohort, Arrowhead has earned a $25 million milestone payment from Janssen Pharmaceuticals, Inc., part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

Christopher Anzalone, Ph.D., president and chief executive officer at Arrowhead, said: “Both Arrowhead and Janssen share the aim to advance transformational medicines that achieve higher rates of functional cure with a finite treatment duration for patients with chronic hepatitis B viral infection. Beginning this new triple combination cohort in our ongoing AROHBV1001 study has the potential to generate valuable data rapidly.”

AROHBV1001 (NCT03365947) is a Phase 1/2 clinical study evaluating the safety, tolerability, and pharmacokinetic effects of single-ascending doses (SAD) of ARO-HBV in healthy adult volunteers, as well as the safety, tolerability, and pharmacodynamic effects of multiple-ascending doses (MAD) of ARO-HBV in patients with chronic HBV.

Arrowhead entered into a license and collaboration agreement with Janssen in October 2018 to develop and commercialize ARO-HBV. Under the initial terms of the HBV license agreement, Arrowhead was eligible to receive a $50 million milestone payment linked to a Phase 2 study. Arrowhead and Janssen subsequently amended the HBV license agreement to accelerate the payment of $25 million of the $50 million Phase 2 milestone with the initiation of cohort 12 of the AROHBV1001 trial. Arrowhead is eligible to receive the remaining $25 million upon the initiation of a Phase 2 study by Janssen.

Hepatitis B infection is a life-threatening viral infection of the liver, which can cause cirrhosis — scarring of liver tissue — and liver cancer if the infection becomes chronic. The World Health Organization cites that hepatitis B is a global public health problem with 257 million people living with the disease, resulting in 887,000 deaths in 2015.1 While a preventive vaccine is available, cure rates for those infected remain low and most patients will endure lifelong therapy.

About Arrowhead Pharmaceuticals

Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing.

For more information, please visit www.arrowheadpharma.com, or follow us on Twitter @ArrowheadPharma. To be added to the Company's email list and receive news directly, please visit http://ir.arrowheadpharma.com/email-alerts.

Safe Harbor Statement under the Private Securities Litigation Reform Act:

This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of various factors and uncertainties, including the safety and efficacy of our product candidates, the duration and impact of regulatory delays in our clinical programs, our ability to finance our operations, the likelihood and timing of the receipt of future milestone and licensing fees, the future success of our scientific studies, our ability to successfully develop and commercialize drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, and the enforcement of our intellectual property rights. Our most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q discuss some of the important risk factors that may affect our business, results of operations and financial condition. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances.

作者: 齐欢畅 时间: 2019-4-25 08:26

作者: StephenW 时间: 2019-4-25 09:14

本帖最后由 StephenW 于 2019-4-25 09:15 编辑

我认为第三种药物可能是他们自己的TLR7激动剂.

https://www.healio.com/hepatology/chronic-hepatitis/news/online/%7B340266ff-3b48-479f-96e3-a6e11f6ccfb2%7D/video-janssen-hbv-pipeline-focuses-on-increasing-functional-cure-rates

VIENNA — In this exclusive video from the International Liver Congress 2019, James Merson, PhD, global therapeutic area head for infectious diseases at Janssen, discusses the company’s pipeline for hepatitis B with a focus on improving functional cure rates.

“For us at Janssen, HBV and being able to increase functional cure rates of patients living with HBV is an important part of our strategy as to how we can manage the disease more effectively than the current treatments do today,” Merson told Healio Gastroenterology and Liver Disease.

“We have a number of different modalities that we’re looking at to increase functional cure rates,” he continued. “Standard of care today — nucleos(t)ide analogues — get around 3% functional cure rates. We’re looking to make a meaningful difference for those patients, so they no longer have to take lifelong therapies to manage their disease.”

Merson provided details on the company’s HBV pipeline that includes two capsid assembly modulators that have shown “impressive” antiviral activity in phase 2a studies, a small interfering RNA molecule that has demonstrated HBV surface antigen suppression in a phase 2a study that continued after 3 months of stopping treatment, and a toll-like receptor 7 agonist that has shown promise in early phase 1 trials.

“As we look forward, we are trying to find the optimal doses and dosing frequency for each of these modulators and how best to combine each one of those with various partners to see whether we can truly increase the functional cure rates in patients chronically infected with HBV rates.”

Reference:

Harrison SA. Abstract SAT-300. Presented at: International Liver Congress; April 10-14, 2019; Vienna, Austria.

Disclosure: Merson is the global therapeutics area head for infectious diseases at Janssen.
维也纳 - 在2019年国际肝病大会的独家视频中，Janssen传染病全球治疗领域负责人James Merson博士讨论了该公司的乙型肝炎管道，重点是提高功能性治愈率。

“对于我们在Janssen，HBV以及能够提高HBV患者的功能治愈率是我们策略的一个重要部分，因为我们比目前的治疗方法更有效地治疗疾病，”Merson告诉Healio Gastroenterology and Liver疾病。

“我们有许多不同的方式，我们正在寻求提高功能治愈率，”他继续说。 “今天的护理标准 - 核苷（酸）类似物 - 大约3％的功能治愈率。我们希望为那些患者创造意义差异，因此他们不再需要终生疗法来治疗他们的疾病。”

Merson提供了该公司HBV管道的详细信息，其中包括两个衣壳装配调节剂，这些调节剂在2a期研究中显示出“令人印象深刻的”抗病毒活性，这是一种小干扰RNA分子，在2a期研究中证实HBV表面抗原抑制，持续3个月后停止治疗，以及在早期1期试验中显示出前景的Toll样受体激动剂。

“在我们展望未来的过程中，我们正在努力寻找每种调节剂的最佳剂量和给药频率，以及如何最好地将这些调节剂中的每一种与各自的合作伙伴相结合，看看我们是否能够真正提高慢性感染患者的功能治愈率。 HBV率。“

参考：

哈里森SA。摘要SAT-300。发表于：国际肝脏大会; 2019年4月10日至14日;维也纳，奥地利。

披露：Merson是Janssen传染病的全球治疗领域负责人。

作者: newchinabok 时间: 2019-4-25 09:22

StephenW 发表于 2019-4-25 09:14
我认为第三种药物可能是他们自己的TLR7激动剂.

有道理。

作者: 左罗 时间: 2019-4-25 10:55

令人欣慰的好消息，当然值得期待！

作者: 左罗 时间: 2019-4-25 11:05

这个东东降HBsAg的效果如何？一定很好吧！

作者: sir 时间: 2019-4-25 11:06

回复 StephenW 的帖子

TLR7也有可能，不过强生的TLR7激动剂目前只完成了phase 1a, phase 1b疗效部分可能还没做，国内正大天晴也还在做phase1a，TLR7的疗效及安全性还没有明确的情况下就联合用药貌似不太合理,除非已经完成了phase1b但是目前没有任何有关的信息

作者: StephenW 时间: 2019-4-25 11:57

回复 sir 的帖子

你或许是正确的, ARO-HBV也仅在1/2期临床试验中, JNJ-4964和ARO-HBV临床试验均在新西兰进行, 在Dr Gane的的监督下.

作者: 乙肝人1949 时间: 2019-4-25 12:53

能不能理个条理?哪三药一块搞

作者: SK蜗牛 时间: 2019-4-25 14:18

这确实是好消息，终于开始三联疗法了，也许可以实现乙肝的功能性治愈，期待

作者: hchu 时间: 2019-4-25 15:38

记得当年的幽门杆菌，自从有了第一个三联疗法，后面就涌出了多个三联疗法，现在是四联疗法，基本是药到菌除。希望成功。问题是不知成功后一个疗程要多少钱。

作者: newchinabok 时间: 2019-4-25 16:42

hchu 发表于 2019-4-25 15:38
记得当年的幽门杆菌，自从有了第一个三联疗法，后面就涌出了多个三联疗法，现在是四联疗法，基本是药到菌除 ...

RNAi药皮下注射，一月一针，三针就降到100以下，就算一针10万，30万也有一半人能承受，就看治愈率如何。更何况不会一针10万

作者: 天上飞鱼 时间: 2019-4-25 17:09

未来联合用药可能会两大方案，理想状态是：RNAI联合核苷和免疫激活药物，价格高，见效快，半年内药到病除；核衣壳抑制剂联合核苷和免疫激活药物，药效慢，价格相对低廉，一年内见效。当然如果两个联合方案均效果不佳，也不排除出现四联方案的可能，RNAI联合核衣壳抑制剂、核苷和免疫药物。

作者: StephenW 时间: 2019-4-25 17:35

天上飞鱼发表于 2019-4-25 17:09
未来联合用药可能会两大方案，理想状态是：RNAI联合核苷和免疫激活药物，价格高，见效快，半年内药到病除； ...

免疫激活药物需要非常低的血清hbvdna和HBsAg.
针对S genes的RNAI只能降低血清HBsAg, 但不能降低血清hbvdna.
核衣壳抑制剂联合核苷可以防止补充cccDNA库, 从长远来看，可以将cccDNA池减少到零. 大三需要更长的时间. 但是来自整合hbvdna的血清HBsAg不能减少.

REPLICOR三联疗法, NAP + TDF + PEGIFN, 已经尝试在小三, 可以提高功能治愈率.
根据REPLICO, 免疫激活药物需要血清HBsAg小于1 iu / ml.

作者: newchinabok 时间: 2019-4-25 18:31

StephenW 发表于 2019-4-25 17:35
免疫激活药物需要非常低的血清hbvdna和HBsAg.
针对S genes的RNAI只能降低血清HBsAg, 但不能降低血清hbvdn ...

免疫激活药物需要非常低的血清hbvdna和HBsAg.此言谬矣! 干挠素治愈病人中，hbsag和hbvDNA高的人不少

作者: StephenW 时间: 2019-4-25 18:46

newchinabok 发表于 2019-4-25 18:31
免疫激活药物需要非常低的血清hbvdna和HBsAg.此言谬矣! 干挠素治愈病人中，hbsag和hbvDNA高的人不少 ...

"干挠素治愈病人中，hbsag和hbvDNA高的人不少" - 但不是太多, 低于10％.

干挠素 + TDF/ETV HBsAg清除率失<20％.

作者: newchinabok 时间: 2019-4-25 18:50

本帖最后由 newchinabok 于 2019-4-25 19:00 编辑

StephenW 发表于 2019-4-25 18:46
"干挠素治愈病人中，hbsag和hbvDNA高的人不少" - 但不是太多, 低于10％.

干挠素 + TDF/ETV HBsAg清除 ...

RNAI+免疫药能不能治病，治愈率有多高？现在下结论太早

作者: 天上飞鱼 时间: 2019-4-25 19:28

很奇怪强生没有公布具体的三联用药方案，难道属于商业机密？或者还没有考虑好到底联合哪一种药物，springbank的sb9200也正在设计联合用药方案，不排除加入联合用药豪华套餐的可能

作者: 齐欢畅 时间: 2019-4-25 20:19

hchu 发表于 2019-4-25 15:38
记得当年的幽门杆菌，自从有了第一个三联疗法，后面就涌出了多个三联疗法，现在是四联疗法，基本是药到菌除 ...

作者: 平凡之路123 时间: 2019-4-25 20:35

如何控制好副作用是关键，干扰素的副作用太强了，如果有免疫药会更好。

作者: mingbai 时间: 2019-4-25 23:04

应该年底有试验结果了吧？天佑乙人。

作者: 齐欢畅 时间: 2019-4-26 18:02

天佑乙人。

作者: 乙肝人1949 时间: 2019-4-26 19:04

前几年陈月杰(北京哪个医院忘记了)在有条件的情况下，核苷+干扰素，治愈率为30%。如果老外今年加入更多药，优化序贯，治愈率期待提高到70-80%，加油啊

作者: 齐欢畅 时间: 2019-4-26 19:35

乙肝人1949 发表于 2019-4-26 19:04
前几年陈月杰(北京哪个医院忘记了)在有条件的情况下，核苷+干扰素，治愈率为30%。如果老外今年加入更多药， ...

作者: 小牡丹 时间: 2019-4-26 19:49

干扰素就是忆苦思甜时代的典型食物。可怜中国的医学家，天天忆苦思甜，迟早会肠梗阻。

作者: 小牡丹 时间: 2019-4-26 19:51

必须撇开干扰素思路，另辟蹊径才能有出路。

作者: 平凡之路123 时间: 2019-4-26 20:13

回复乙肝人1949 的帖子

效果应该没有这么好。基本上表抗低于1500，病毒阴性就具备干扰素条件了。干扰素可以进一步降低表抗，但是副作用也大，能撑到表抗阴性的，可能也就10%了。

作者: 乙肝人1949 时间: 2019-4-26 21:01

治愈率慢慢提高也是一种思路。另一种思路就是毕其功于一役，一锤子搞定。如清霉素治感染。都可以尝试，那个陈月杰的成果咱们平常心看待

作者: 齐欢畅 时间: 2019-4-26 23:10

其实联合用药的可能性还有很多，大家不要灰心。不过，干扰素治愈率10%是有的。联合用药肯定会更好的效果。我倒看好新加坡莱恩公司的tcr -t疗法

作者: 齐欢畅 时间: 2019-4-26 23:12

而早在2018年6月，Lion TCR已经筹集了2000万美元的A轮融资，资金正是用于其在中国和新加坡的主要医院推行其领先的候选产品LioCyx™(针对肝癌—HCC的个性化HBV特异性TCR-T细胞疗法)正在进行的临床试验，以及扩大其产品管线，包括对抗病毒相关的实体瘤和清除慢性乙型病毒性肝炎。

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