Drugs in Development: Update

StephenW

Drugs in Development:  Update
                   —Alan Franciscus, Editor-in-Chief                                   

GS-7977
                                                                      On March 6, 2012 interim results from an arm of the  ELECTRON phase 2 study were released at the Conference on Retroviruses and  Opportunistic Infections (CROI).  This  particular arm treated HCV genotype 1, prior null responders—the hardest group  to retreat—with GS-7977 (HCV polymerase inhibitor) plus ribavirin (RBV) (no  interferon (PEG)).  The arm enrolled 10  patients who were treated for 12 weeks with GS-7977 plus ribavirin.  Of the nine patients who were HCV RNA  undetectable at the end of treatment, eight patients relapsed within 4 weeks  post treatment.  One patient who did  achieve SVR12 had favorable predictors of successful response—female,  Caucasian, IL28B CC genotype and a low fibrosis score.

                                  

Comments:  This is very disappointing news in the light  of all of the positive stories about GS-7977/RBV therapy (without interferon)  that have been released.  But it is  important to keep in mind a couple of important issues when interpreting these  results:  

                  

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  The null responder population is and will be  the most difficult to treat population.   GS-7977 plus ribavirin in genotypes 2 and 3 has cure rates in phase 2  studies of up to 100% and HCV genotype 1 treatment-naïve patients in phase 2  studies have had up to 91% cure rates.

•                      

  In this difficult to treat population there is  most likely a need to add another direct acting antiviral (DAA) or treat for a  longer period of time.  Gilead has an  entire portfolio of other DAAs that can be combined with GS-7977 including  GS-9256—HCV protease inhibitor, and GS-9190—HCV polymerase inhibitor.

•                      

  There are two other interferon-free  collaborations of GS-7977 with other pharmaceutical companies:

  
  
  •                         

    BMS’s daclatasvir—NS5A inhibitor with GS-7977 with and  without RBV, and

  •                         

    Tibotec’s TMC435—HCV protease inhibitor with and without  RBV.

    
    

                  

The bottom line is not to give up hope—we will get to the  100% cure rates for genotypes 1, 2, 3, 4, 5, and 6 eventually—it’s just a  matter of finding the right combination of drugs and the optimal treatment  durations—that’s what clinical trials are all about.

StephenW

在发展中的药物：更新
艾伦·弗朗西斯，编辑，首席

GS-7977
3月6日，电子2期研究的手臂从2012年中期业绩公布的逆转录病毒和机会性感染（CROI）会议。这种特殊的手臂治疗丙型肝炎病毒基因型1，前空反应最难的一组撤退，GS-7977（丙型肝炎病毒聚合酶抑制剂）加病毒唑（利巴韦林）（无干扰素（PEG））。手臂招收10人与GS-7977加利巴韦林治疗12周的患者。九个人丙型肝炎病毒RNA在治疗结束时检测不到的患者，8例复发治疗后4个星期内。一个病人没有实现SVR12有利的预测成功应对女性，白人，IL28B CC基因型和低纤维化评分。

评论：这是在所有有关GS-7977/RBV治疗积极的故事（不包括干扰素）已发布的消息非常失望。但重要的是在解释这些结果时，要记住几个重要问题：

    空应答人口，将是最难以治疗的人口。 GS-7977基因型2和3加利巴韦林治疗率在相2 100％和丙型肝炎病毒基因型1治疗天真的有2项研究，治愈率高达91％的患者在第一阶段的研究。

    在这个艰难的治疗人群是最有可能需要添加另一个直接作用抗病毒药物（的DAA）或一个较长时间的治疗。 Gilead公司拥有的GS-7977 GS-9256-HCV蛋白酶抑制剂，GS-9190-HCV聚合酶抑制剂，可以结合其他DAAS整个投资组合。

    还有其他两个GS-7977-干扰素免费与其他制药公司的合作：

        拜耳的daclatasvir GS-7977-NS5A的抑制剂与无利巴韦林，

        Tibotec公司的TMC435-HCV蛋白酶抑制剂与利巴韦林和无。

底线并不是放弃希望，我们将得到的基因型1，2，3，4，5和6的100％痊愈率最终，它是刚刚1找到的药物正确的结合问题和最佳的治疗工期，这是临床试验都是。