丙肝鸡尾酒疗法

　　2015年2月19日，FDA批准艾伯维的全口服无干扰素治疗方案VIEKIRA PAK，该方案用于治疗慢性基因1型(GT1)丙型肝炎病毒感染患者，也可用于HCV/HIV-1合并感染(丙肝病毒合并人类免疫缺陷病毒1型)患者和肝移植患者。

　　Viekira Pak是一种全口服无干扰素丙肝鸡尾酒疗法，由固定剂量ombitasvir/paritaprevir/ritonavir(25mg/150mg/100mg，每日一次)和dasabuvir(250mg，每日两次)组成。根据Viekira Pak的处方信息，该治疗方案的推荐用量为：

　　每天2片固定剂量组合(ombitasvir/paritaprevir/ritonavir，12.5mg/75mg/50mg，早餐时服药)和每日2片dasabuvir(250mg，早餐、晚餐时各服一片)。

　　背景资料

　　2014年3月4日讯 /生物谷BIOON/ --目前，艾伯维(AbbVie)正稳步推进其丙肝鸡尾酒疗法。在第21届逆转录病毒和机会性感染大会(CROI 2014)上，该公司公布的关键III期M13-961(PEARL-III)研究的详实数据表明，其所开发的丙肝鸡尾酒疗法对难治性丙肝群体的治愈率几乎达到了100%。

　　AbbVie开发的丙肝鸡尾酒疗法由固定剂量ABT-450/ritonavir/ABT-267(150mg/100mg/25mg，每日一次)和ABT-333(250mg，每日2次)有或无利巴韦林(基于体重，每日2次)组成。ABT-450、ABT-267、ABT-333三者分别具有不同的作用机制，能够中断HCV复制过程，

　　PEARL-III研究仅是AbbVie丙肝鸡尾酒疗法临床项目的6个III期研究之一，该公司预计于下一季度向FDA提交监管文件。而竞争对手吉利德(Gilead)已在2月份向FDA提交了其鸡尾酒疗法(ledipasvir/sofosbuvir)的监管文件。双方均预计在今年将各自的丙肝鸡尾酒疗法推向市场。不过，值得注意的是，这2家公司在其2014年指南中均未提及各自鸡尾酒疗法的销售预期。

　　关于PEARL-III研究：

　　PEARL-III是一项全球性、多中心、随机、双盲、安慰剂对照研究，在初治(treatment-naive)非肝硬化基因型1b HCV成人感染者中开展，评估了AbbVie丙肝鸡尾酒疗法单独及联合利巴韦林(RBV)用于为期12周治疗的疗效和安全性。

　　该项研究包含419名无肝硬化证据的初治基因型1b感染者，209名患者随机分配接受12周的鸡尾酒疗法(无利巴韦林)，210名患者接受12周的鸡尾酒疗法和利巴韦林治疗。接受鸡尾酒疗法(无利巴韦林)的患者组有99.0%(n=207/209)的患者在治疗12周后实现了持续病毒学应答(SVR12)，鸡尾酒+利巴韦林组有99.5%(n=209/210)的患者实现SVR12。鸡尾酒疗法(无利巴韦林)治疗组以安慰剂代替利巴韦林。

　　该项研究达到了主要重点和次要终点。同时，在治疗后12周内，未记载到任何病情复发病例。(生物谷Bioon.com)

　　英文原文：AbbVie's hep C cocktail aces its latest PhIII study with a sky-high cure rate

　　BOSTON, March 3, 2014 /PRNewswire/ -- The first detailed results from AbbVie's (NYSE: ABBV) pivotal phase III study, PEARL-III, were presented today as part of the 21st Conference on Retroviruses and Opportunistic Infections (CROI) press conference and will also be presented as a late-breaker at the conference on March 4. PEARL-III evaluated the efficacy and safety of 12 weeks of treatment with AbbVie's investigational therapy with or without ribavirin (RBV) in non-cirrhotic, adult patients with chronic genotype 1b (GT1b) hepatitis C virus (HCV) infection who were new to treatment.

　　The PEARL-III study met its primary and secondary endpoints. In the 419-patient study, sustained virologic response rates 12 weeks post-treatment (SVR12) of 99.5 and 99.0 percent were achieved with the AbbVie regimen with and without RBV, respectively. There were no study drug discontinuations due to adverse events.

　　"Results from PEARL-III are encouraging, as they demonstrate AbbVie's regimen can achieve high rates of SVR, with and without ribavirin across several patient characteristics in those with genotype 1b chronic hepatitis C infection," said Peter Ferenci, M.D., professor of Gastroenterology and Hepatology, Medical University of Vienna.

　　PEARL-III enrolled patients across different demographics and characteristics. Response rates in patients with certain characteristics (male gender, Black race and IL28B non-CC genotypes) were examined, as these patient populations have historically been associated with having a decreased response to treatment. High response rates were observed across all patients in the study, including those with these characteristics.

　　"We are excited about the strong PEARL-III results which demonstrate the AbbVie regimen achieved high SVR rates with no discontinuations due to adverse events in patients new to treatment with genotype 1b infection," said Scott Brun, M.D., vice president, pharmaceutical development, AbbVie. "Additionally, with these data, we continue to be on track to begin major regulatory submissions in the second quarter of 2014. AbbVie will continue to disclose additional detailed phase III study results at future scientific congresses and in publications."

　　About Study M13-961 (PEARL-III)

　　PEARL-III is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with AbbVie's regimen with and without RBV in non-cirrhotic, GT1b HCV-infected, treatment-naive adult patients.

　　The study population consisted of 419 GT1b treatment-naive patients with no evidence of liver cirrhosis: 209 patients randomized to the regimen without RBV for 12 weeks, and 210 patients randomized to the regimen with RBV for 12 weeks. Following 12 weeks of treatment, 99.0 percent receiving the regimen without RBV (n=207/209) and 99.5 percent receiving the regimen with RBV (n=209/210) achieved SVR12. Patients in the treatment arm without RBV received placebo in substitution for RBV.

　　Patients with different demographics and characteristics were enrolled in the study, including gender, race (Black vs. non-Black), Hispanic/Latino ethnicity, age, geographic region, body mass index (BMI), liver fibrosis stage, IL28B genotype and viral load.

　　Across treatment arms in PEARL-III, there were no documented relapses within 12 weeks post-treatment. No on-treatment virologic failures occurred in the treatment arm without RBV and a single virologic failure occurred in the treatment arm with RBV. While all patients in the study completed therapy, two patients in the arm without RBV were lost to follow-up and therefore were considered treatment failures.

　　The most commonly reported adverse events (>10 percent for either arm) were headache, fatigue, pruritus, nausea and asthenia, with pruritus and nausea occurring at a statistically higher rate in the treatment arm with RBV compared to the arm without RBV. Anemia occurred more commonly among patients in the RBV-containing arm with clinically significant anemia requiring RBV dose reductions occurring in 9 percent of these patients.

　　Additional information about AbbVie's phase III studies can be found onwww.clinicaltrials.gov.

　　About AbbVie's Investigational HCV Regimen

　　The AbbVie investigational regimen consists of the fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ABT-267 (25mg), dosed once daily, and ABT-333 (250mg) with or without RBV (weight-based), dosed twice daily. The combination of three different mechanisms of action interrupts the HCV replication process with the goal of optimizing SVR rates across different patient populations.

　　AbbVie's HCV Development Program

　　The AbbVie HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating an interferon-free, all-oral regimen with and without RBV with the goal of producing high SVR rates in as many patients as possible, including those that typically do not respond well to treatment, such as previous non-responders to interferon-based therapy or patients with advanced liver fibrosis or cirrhosis.

　　ABT-450 was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors. ABT-450 is being developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of HCV.

　　Safety Information for Ribavirin and Ritonavir

　　Ribavirin and ritonavir are not approved for the investigational use discussed above, and no conclusions can or should be drawn regarding the safety or efficacy of these products for this use.

　　There are special safety considerations when prescribing these drugs in approved populations.

　　Ritonavir must not be used with certain medications due to significant drug-drug interactions and in patients with known hypersensitivity to ritonavir or any of its excipients.

　　Ribavirin monotherapy is not effective for the treatment of chronic hepatitis C virus and must not be used alone for this use. Ribavirin causes significant teratogenic effects and must not be used in women who are pregnant or breast-feeding and in men whose female partners are pregnant. Ribavirin must not be used in patients with a history of severe pre-existing cardiac disease, severe hepatic dysfunction or decompensated cirrhosis of the liver, autoimmune hepatitis, hemoglobinopathies, or in combination with peginterferon alfa-2a in HIV/HCV co-infected patients with cirrhosis and Child-Pugh score greater than or equal to 6.

　　See approved product labels for more information.

　　About AbbVie

　　AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. AbbVie employs approximately 25,000 people worldwide and markets medicines in more than 170 countries.

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