EASL2012:Non-Interferon-Based Combination Therapy Offers High Response Rates for

StephenW

Source: DGNews  |  Posted 6 days ago
Non-Interferon-Based Combination Therapy Offers High Response Rates for Hepatitis C Patients: Presented at EASL

Tags:
• Hepatitis
• interferon
• peginterferon alfa-2a
• peginterferon alfa-2b
• peginterferon beta-1a
• ribavirin
• ritonavir
  

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By Chris Berrie
BARCELONA, Spain -- April 25, 2012 -- Combining ABT-450 with ritonavir
(ABT-450/r) plus ABT-333 plus ribavirin (RBV) is well tolerated, provides high
sustained virological response (SVR) in treatment-naïve patients infected with
hepatitis C virus (HCV) genotype 1, and shows relatively high SVR in previous
interferon-based nonresponders, researchers said here at the 47th Annual
Meeting of the European Association for the Study of the Liver (EASL).
At present, there are no treatment options for HCV-infected patients who are
ineligible or intolerant to the interferons.
“This is the first study combining ABT-450 with ABT-333 with ribavirin without
interferon in genotype 1 patients who were either treatment-naïve or previous
treatment failures,” stated Fred Poordad, MD, Chief of Hepatology and Liver
Transplantation at the Comprehensive Transplant Center of Cedars-Sinai Medical
Center, Los Angeles, California, presenting this open-label study here on April
21.
The study design included 3 arms, the first 2 of which treated naïve patients
with chronic HCV genotype 1 infection using ABT-333 400 mg twice daily plus RBV
1,000-1,200 mg once daily plus ABT-450/r either 250/100 mg once daily (arm 1; n
= 19) or 150/100 mg once daily (arm 2; n = 14). The third treatment arm was
similar to arm 2, but treated prior partial or null responders to previous
pegylated interferon plus RBV treatments (arm 3; n = 17).
The treatments were for 12 weeks, with 48 weeks follow-up.
These patients were mainly male, with a mean age of just over 50 years, and
were largely HCV genotype 1a. For IL28B genotype, 52.6% were CC in arm A and
35.7% in arm B, with no IL28B CC in arm 3.
The primary endpoint was extended rapid virological response (eRVR) based on
HCV RNA lower than the limit of detection from treatment weeks 4 to 12. As the
intent-to-treat analysis, these reached 90%, 79% and 59% in arms 1, 2, and 3,
respectively.
Similarly, for SVRs at weeks 4 (SVR4) and 12 (SVR12), high levels of response
were achieved for arms 1 (95%, 93%, respectively) and 2 (95%, 93%). These SVR4
and SVR12 responses were also relatively high for the previous nonresponding
patients in arm 3 (47%, 47%).
Comparisons across IL28B CT versus TT showed no differences in SVR12 either for
treatment-naïve patients, as arms 1 plus 2 (100% vs 100%) or for previous
nonresponders (50% vs 40%).
Based on clonal sequencing, Dr. Poordad highlighted the resistant variants at
baseline and at virologic failure in the previous nonresponders of arm 3. “It
is important to note that patients who had virologic failure developed
resistance variants to both the protease inhibitor as well as the polymerase
inhibitor,” he noted.
In the safety analysis, there were no deaths or serious adverse events
throughout, with only 1 adverse event leading to premature discontinuation, in
arm 1. Four patients showed adverse events assessed as severe, without
requiring study-drug interruption or discontinuation: hyperbilirubinaemia,
fatigue, pain, and vomiting.
The treatment-emergent adverse events and the laboratory abnormalities noted
were largely the same type and levels across the 3 treatment arms. Dr. Poordad
also noted that the transient asymptomatic elevation of indirect bilirubin that
was seen is consistent with the known effect of ABT-450 on the bilirubin
transporter OATO1B1.
“It does appear that ABT-450 with ritonavir, ABT-333 plus ribavirin for 12
weeks has the potential to achieve very high SVR in a high proportion of
patients without interferon,” he concluded.
Funding for this study was provided by Abbott.
[Presentation title: A 12-Week Interferon-Free Regimen of ABT-450/r +
ABT-333 + Ribavirin Achieved SVR12 in More Than 90% of Treatment-Naïve HCV
Genotype-1 Infected Subjects and 47% of Previous Non-responders. Abstract 1399]

StephenW

来源：DGNews |发表于6天前
非干扰素为基础的联合治疗丙型肝炎患者提供很高的应答率
：提交欧洲肝病学会

    标签：
        肝炎
        干扰素
        聚乙二醇干扰素α-2a
        聚乙二醇干扰素α-2b干扰素
        聚乙二醇干扰素β-1A
        利巴韦林
        利托那韦

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克里斯·贝里

巴塞罗那，西班牙 -  2012年4月25日 - 结合与ritonavir ABT生根粉-450
（ABT-450 / R），加上ABT-333加病毒唑（利巴韦林）是很好的耐受性，提供高
持续病毒学应答（SVR）在治疗过的患者感染
丙型肝炎病毒（HCV）基因1型，并显示相对高的SVR在以前的
干扰素为基础的无反应，研究人员说，在第47届
肝（EASL）研究欧洲协会的会议。

目前，丙型肝炎病毒感染的病人谁没有治疗方案
不合格或不能耐受的干扰素。

“这是第一次研究，结合利巴韦林ABT-450 ABT-333没有
1谁是天真或以前任何治疗的患者中基因型干扰素
弗雷德说：“Poordad，医学博士，首席肝病和肝治疗失败，
在Cedars-Sinai医学综合移植中心的移植
中心，洛杉矶，加利福尼亚，提出这个开放标签研究，于4月
21。

研究设计包括3个武器，其中治疗初治患者的第2
慢性丙型肝炎病毒基因型1感染使用ABT生根粉-333 400 mg，每天两次加利巴韦林
1,000-1,200毫克，每天一次加ABT生根粉-450 / R 250/100毫克，每天一次（臂1例
（臂2 = 14）= 19）或150/100毫克，每天一次。第三个治疗组为
以前手臂2类似，但治疗前部分或空反应
聚乙二醇干扰素加利巴韦林治疗（手臂3，N = 17）。

治疗12周，于48周随访。

这些患者主要是男性，平均年龄刚过50岁了，和
主要是丙型肝炎病毒基因型1A。 IL28B基因型，52.6％，CC在ARM和
在B组的35.7％，无臂3 IL28B消委会。

主要终点是延长的基础上快速病毒学应答（eRVR）
丙型肝炎病毒RNA比从4至12周的治疗检测限低。作为
意向性治疗分析，这些达到90％，79％和59％的武器1，2，3，
分别。

同样，对于SVRS周4（SVR4的）和12（SVR12），高响应水平
取得了武器1（95％，93％，分别）和2（95％，93％）。这些的SVR4
和SVR12的反应也比较高，以前无响应
手臂3例（47％，47％）。

跨IL28B CT与TT比较表明：在SVR12无显着差异，无论是对
治疗过的病人，作为武器1加2（100％和100％）或以前
无效（50％比40％）。

基于克隆测序，博士Poordad强调耐药变异
基线和手臂3以前无效的病毒学失败。 “这
重要的是要注意患者有病毒学失败发达
蛋白酶抑制剂，以及作为聚合酶的抵抗变种
抑制剂，“他说。

在安全性分析，有没有死亡或严重不良事件
各地，只有1不良事件导致过早停药，
手臂1。四名患者表现评定为严重不良事件，无
需要研究药物中断或终止：高胆红素血症，
疲劳，疼痛，呕吐。

治疗出现的不良事件和实验室异常指出
是大致相同的跨越3个治疗武器的类型和水平。博士Poordad
还指出，间接胆红素的瞬态无症状海拔
被视为与胆红素称为ABT-450的效果是一致的
转运OATO1B1。

“这确实出现与利托那韦，ABT-333加利巴韦林12 ABT-450
几个星期以来，在高的比例可能达到非常高的SVR
无干扰素的患者，他的结论。“

雅培为这项研究提供了资金。

[演讲题目：一项为期12周的ABT-450 / R-干扰素免费养生+
ABT-333 +利巴韦林取得超过90％的朴素治疗丙型肝炎病毒SVR12
基因型1感染者和47％以前的非应答。摘要1399]