Arrowhead Begins Dosing the Phase 2b MONARCH Combination Study of ARC-520 in Patients with Chronic Hepatitis B Infection
PASADENA, Calif.--(BUSINESS WIRE)-- Arrowhead Research Corporation (NASDAQ: ARWR), a biopharmaceutical company developing targeted RNAi therapeutics, dosed the first patient in the Phase 2b MONARCH combination study of ARC-520, it's RNAi-based drug for the treatment of chronic hepatitis B virus (HBV) infection. The clinical trial is currently enrolling patients at multiple centers in Australia and New Zealand. MONARCH is intended to identify one or more combinations of ARC-520 and other therapeutic agents that can potentially lead to a functional cure of chronic HBV.
"We recently reported clinical data from our Phase 2a study at AASLD showing that a single dose of ARC-520 can achieve a reduction of up to 99% in hepatitis B surface antigen, and nonclinical data at HepDART showing that multiple doses of ARC-520 were associated with immune reactivation in 7 of 9 chimpanzees studied. These data make us very eager to see results as they emerge from MONARCH and our other multiple dose studies," said Christopher Anzalone, Ph.D., Arrowhead president and CEO. "The goal of MONARCH is to identify one or more combinations of ARC-520 and other agents that enable functional cures in patients. If we can achieve this, it would represent a big leap forward in the field and provide hope for the more than 350 million people worldwide chronically infected with the hepatitis B virus."
The MONARCH study, also called Heparc-2008, is a multicenter, open-label study to evaluate ARC-520 administered alone and in combination with other therapeutics in patients with chronic hepatitis B virus infection. The primary outcome measure is the percentage of patients achieving a 1-log reduction in hepatitis B surface antigen (HBsAg) compared to baseline. Secondary outcome measures include the percentage of patients achieving HBsAg loss and time to HBsAg loss based on qualitative assay, percentage of patients achieving anti-HBs seroconversion and time to anti-HBs seroconversion (antibody to HBsAg), percentage of patients achieving a 1-log reduction in HBsAg and achieving a HBsAg level less than 100 IU/L, as well as other outcome measures.
The initial six cohorts are each planned to consist of up to twelve treatment naïve patients. Patients in cohort 1 will receive ARC-520 as monotherapy once every 4 weeks for 48 weeks (13 doses). Patients in cohorts 2-6 will be stratified by e-antigen status and HBV genotype. They will receive the same regimen of ARC-520 for 48 weeks in combination with daily entecavir for 60 weeks and pegylated interferon alpha 2a (PEG IFN) for 48 weeks. MONARCH is designed to allow for new cohorts to be added that test additional dosing regimens and different combinations as new agents become available for study. 作者: StephenW 时间: 2016-1-8 04:33
这个消息发布后，yahoo财经消息论坛上一堆strong buy的评论，希望16年是突破的一年。
我看到有人分析也许五月份应该会有可靠地消息出来，下面是一个人的评论，这个人的个人观点而已哈：
After Manetta's response one can predict the outcome leading to FC.
After 5 dosings plot of Manettta's HBsAg levels strongly indicated Sustained Viral Response as later confirmed in post treatment HBsAg levels. Taken into consideration fact that chimps do not have immune system as well evolved as humans (at least in case of HBV resistance), the signs of human SVR or even FC might be there before the 5th dosing. THe case of Manetta and other chimps give a metric to which human responses can be evaluated. Analyzing the data management can with some certitude have knowledge about the outcome of Monarch even before the full course of treatment. At the latest this can be after 5th dosing.
大意是说Manetta（出现免疫应答的那个大猩猩的名字）在注射了5个dose之后出现了持续的病毒应答。考虑到猩猩没有人类的免疫系统进化的好（至少在对抗hbv方面），人类的持续病毒应答甚至功能治愈应当出现在5个dose之前。所以根据一个月一个dose的进度来看，有人预估也许5月份之前open label的结果就能说明情况。
