Arrowhead and Collaborator Janssen Present Phase 2 Clinical Data for Investigati

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Arrowhead and Collaborator Janssen Present Phase 2 Clinical Data for Investigational Hepatitis B Regimens at The Liver Meeting® 2019
Nov 8, 2019 at 8:00 AM EST
PASADENA, Calif. --(BUSINESS WIRE)--Nov. 8, 2019-- Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today announced Phase 2 clinical data on a double combination of JNJ-3989 (formerly ARO-HBV) and a nucleos(t)ide analog (NA), and the first clinical data on a triple combination of JNJ-3989, JNJ-6379,
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PASADENA, Calif.--(BUSINESS WIRE)--Nov. 8, 2019-- Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today announced Phase 2 clinical data on a double combination of JNJ-3989 (formerly ARO-HBV) and a nucleos(t)ide analog (NA), and the first clinical data on a triple combination of JNJ-3989, JNJ-6379, and an NA, with collaborator Janssen Pharmaceuticals, Inc., part of the Janssen Pharmaceutical Companies of Johnson & Johnson. The data is being presented in two poster presentations at The Liver Meeting®, the Annual Meeting of the American Association for the Study of Liver Disease (AASLD).

Janssen is currently conducting Phase 2b studies of JNJ-3989 in combination with JNJ-6379 and an NA for the treatment of chronic hepatitis B virus infection. Arrowhead entered into a license and collaboration agreement with Janssen in October 2018 to develop and commercialize JNJ-3989.

JNJ-3989 is a liver-targeted investigational antiviral therapeutic for subcutaneous injection designed to treat chronic HBV (CHB) infection via the ribonucleic acid interference (RNAi) mechanism. JNJ-6379 is an investigational orally administered capsid assembly modulator of the class that forms normal capsid structures (CAM-N).

Poster Details:

Dose Response with the RNA Interference Therapy JNJ-3989 Combined with Nucleos(t)ide Analogue Treatment in Expanded Cohorts of Patients with Chronic Hepatitis B

Publication Number: 0696
Session: Hepatitis B - Therapeutics: New Agents
Session Date and Time: November 8, 2019 from 8:00 AM to 5:30 PM EST
Location:  Hynes Convention Center, Hall B
Authors: Dr. Edward J. Gane, et al.
Key points presented include the following:

In the AROHBV1001 study in CHB patients, JNJ-3989 in combination with an NA had strong activity against hepatitis surface antigen (HBsAg), HBV DNA and HBV RNA. Reductions in hepatitis B e antigen (HBeAg) and hepatitis B core-related antigen (HBcrAg) were generally less pronounced
HBsAg reductions were similar in HBeAg positive and HBeAg negative patients
Expanded cohorts with 100–400 mg JNJ-3989 confirmed previous findings that HBsAg declines were similar with these doses; 97% (31/32) of these patients achieved a ≥1.0 log10 (90%) reduction in HBsAg
The 25 mg and 50 mg JNJ-3989 doses were active in reducing HBsAg, and appeared less effective than higher doses
HBsAg responses with JNJ-3989 are consistent with its ability to silence HBV RNA from cccDNA and host-integrated viral DNA (which is a major source of HBsAg in certain CHB populations)
JNJ-3989 was well tolerated at doses up to 400 mg Q4w for three doses.
Overall, JNJ-3989 demonstrated anti-HBV characteristics desirable for an effective RNAi therapy
First Clinical Experience with RNA Interference [RNAi]-Based Triple Combination Therapy in Chronic Hepatitis B (CHB): JNJ-73763989 (JNJ-3989), JNJ-56136379 (JNJ-6379) And a Nucleos(T)ide Analogue (NA)

Publication Number: LP4
Session: Late-Breaking Poster Session
Session Date and Time: November 11, 2019 from 8:00 AM to 5:30 PM EST
Location:  Hynes Convention Center, Hall B
Authors: Dr. Man-Fung Yuen, et al.
Key points presented include the following:

This is the first study to investigate the safety and efficacy of a triple combination of an RNAi (JNJ-3989 200 mg 3x Q4w, three doses), a CAM-N (JNJ-6379 250 mg daily for 12 weeks) and an NA (daily) in patients with CHB
This triple combination was well tolerated, and all CHB patients achieved robust reductions in HBsAg, HBV DNA, and HBV RNA. Reductions in HBeAg and HBcrAg were generally less pronounced during the dosing period
All patients (n=12) achieved a ≥1.0 log10 IU/mL (90%) reduction (nadir ranged from –1.01 to –2.26 log10 IU/mL) in HBsAg
HBsAg reductions were similar in HBeAg positive and HBeAg negative patients
Studies of longer duration with this triple combination are underway aimed at assessing functional cure rates in patients with CHB
Copies of the poster presentations can be accessed on the Events and Presentations page under the Investors section of the Arrowhead website.

Hepatitis B infection is a life-threatening viral infection of the liver, which can cause cirrhosis — scarring of liver tissue — and liver cancer after prolonged period of chronic infection. The World Health Organization cites that hepatitis B is a global public health problem affecting 292 million people worldwide.1 While a preventive vaccine is available, cure rates for those infected remain low and most patients will endure lifelong therapy.

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Key points presented include the following:

This is the first study to investigate the safety and efficacy of a triple combination of an RNAi (JNJ-3989 200 mg 3x Q4w, three doses), a CAM-N (JNJ-6379 250 mg daily for 12 weeks) and an NA (daily) in patients with CHB
This triple combination was well tolerated, and all CHB patients achieved robust reductions in HBsAg, HBV DNA, and HBV RNA. Reductions in HBeAg and HBcrAg were generally less pronounced during the dosing period
All patients (n=12) achieved a ≥1.0 log10 IU/mL (90%) reduction (nadir ranged from –1.01 to –2.26 log10 IU/mL) in HBsAg
HBsAg reductions were similar in HBeAg positive and HBeAg negative patients
Studies of longer duration with this triple combination are underway aimed at assessing functional cure rates in patients with CHB

tianxinheyi

边缘

这个结果很不错啊，表抗的降低那么多，关键是人数达到90%，感觉比Assembly的那个还数据还好一些

newchinabok

边缘 发表于 2019-11-18 15:19
这个结果很不错啊，表抗的降低那么多，关键是人数达到90%，感觉比Assembly的那个还数据还好一些 ...

人体病毒总量很大，降百分之九十九，剩下百分之一也惊人

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如果免疫可以继续，降低到99.99%呢，可能就可以了，如果两种药物协同作用，降低99.99%也是可能的。

aiyayao

newchinabok 发表于 2019-11-18 15:39
人体病毒总量很大，降百分之九十九，剩下百分之一也惊人

All patients had HBsAg >100 IU/mL on Day 1 and 10/12 patients achieved HBsAg <100 IU/mL after 12 weeks of therapy with JNJ-3989, JNJ-6379 and an NA

引自：http://ir.arrowheadpharma.com/static-files/6d7edbe7-c5a2-46c5-9990-a9cdfec854a9
【Figure 3】

12个里面有10个 HBsAg <100 IU/mL  ， 根据之前的研究 100IU/mL 是个比较有希望的清除临界点，并没有你认为的百分之1也惊人

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aiyayao

来自台湾学者的一项自然史研究[53纳入了2491例HBeAg阴性的非肝硬化的慢性HBV感染者，对其HBsAg的转阴影响因素进行前瞻性研究观察，发现基线时的HBsAg定量水平可预测此类患者HBsAg的阴转。如果基线时HBsAg定量水平小于100IU／mL。则出现HBsAg阴转的相对危险度值为10．96．如果联合HBVDNA阴性的话，则预测患者5年和10年HBsAg清除率的准确度分别为89％和84％。这项研究说明了HBsAg定量对于没有进行抗病毒治疗患者的预后判断具有一定作用。

引自： http://www.cccm-em120.com/shiyongjianyanguokan/2014/241.pdf  【HBsAg和HBeAg定量检测的临床应用及意义】

箭头的3联实验，接近百分90可以降低到 100IU／mL 以下，那么在未来是非常有可能实现HBsAg转阴的

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aiyayao 发表于 2019-11-20 23:05
来自台湾学者的一项自然史研究[53纳入了2491例HBeAg阴性的非肝硬化的慢性HBV感染者，对其HBsAg的转阴影响因 ...