美国食品和药物管理局批准Gilead公司的Sovaldi （ TM ） （ Sofosb

StephenW

www.natap.org
U.S. Food and Drug Administration Approves Gilead's Sovaldi(TM) (Sofosbuvir) for the Treatment of Chronic Hepatitis C                                                                                                      U.S. Food and Drug Administration Approves Gilead’s Sovaldi™       (Sofosbuvir) for the Treatment of Chronic Hepatitis C                                                                                                                                              – Sovaldi Approved for Use in Genotypes 1, 2, 3 or 4 –   
      – High Cure Rates (SVR12) and Shortened, 12-Week Course of Therapy       for Many Patients –   
      – First Ever Oral Treatment Regimen for Genotypes 2 or 3 –   
      – First Regimen for Patients Awaiting Liver Transplantation to       Prevent HCV Recurrence –   


FOSTER CITY, Calif.--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the U.S. Food       and Drug Administration (FDA) has approved Sovaldi™ (sofosbuvir) 400 mg       tablets, a once-daily oral nucleotide analog polymerase inhibitor for       the treatment of chronic hepatitis C (CHC) infection as a component of a       combination antiviral treatment regimen. Sovaldi’sefficacy       has been established in subjects with hepatitis C virus (HCV) genotypes       1, 2, 3 or 4 infection, including those with hepatocellular carcinoma       meeting Milan criteria (awaiting liver transplantation) and those with       HCV/HIV-1 co-infection. Recommended regimens and treatment duration for       Sovaldi combination therapy in HCV mono-infected or HCV/HIV-1       co-infected patients follows:   

“In       clinical studies, Sovaldi in combination with other agents achieved very       high cure rates while shortening the duration of treatment to as little       as 12 weeks and reducing or completely eliminating the need for       interferon injections, depending on the viral genotype.”

   

					Treatment					Duration
Genotype 1 or 4					Sovaldi + peg-interferon alfa + ribavirin					12 weeks
Genotype 2					Sovaldi + ribavirin					12 weeks
Genotype 3					Sovaldi + ribavirin					24 weeks

      Sovaldi in combination with ribavirin for 24 weeks can be considered for       CHC patients with genotype 1 infection who are interferon ineligible.       Additionally, Sovaldi should be used in combination with ribavirin for       treatment of CHC patients with hepatocellular carcinoma awaiting liver       transplantation for up to 48 weeks or until liver transplantation to       prevent post-transplant HCV infection. Treatment regimen, duration and       response to Sovaldi are dependent on viral genotype and patient       population, and associated baseline factors. Monotherapy is not       recommended. Full Prescribing Information will be available on www.Gilead.com.   
      The FDA granted Sovaldi Priority Review and Breakthrough Therapy       designation, which is granted to investigational medicines that may       offer major advances in treatment over existing options.   
      “I believe that Sovaldi will have a major impact on public health by       significantly increasing the number of Americans who are cured of       hepatitis C,” said Ira Jacobson, MD, Chief of the Division of       Gastroenterology and Hepatology, Weill Cornell Medical College, New York       City and a principal investigator in the Sovaldi clinical trials. “In       clinical studies, Sovaldi in combination with other agents achieved very       high cure rates while shortening the duration of treatment to as little       as 12 weeks and reducing or completely eliminating the need for       interferon injections, depending on the viral genotype.”   
      Chronic hepatitis C affects an estimated 4 million people in the United       States, the majority of whom are “baby boomers” – individuals born       between 1945 and 1965. The disease is the nation’s leading cause of       liver cancer and liver transplantation, and in recent years has       surpassed HIV/AIDS as a cause of death. The current standard of care for       HCV involves up to 48 weeks of therapy with a pegylated interferon       (peg-IFN)/ribavirin (RBV)-containing regimen, which may not suitable for       certain types of patients.   
      “It is our hope that Sovaldi will mark the beginning of a new era in       hepatitis C treatment. Gilead is proud to have played a role in bringing       about this important therapeutic advance and we would like to extend our       thanks to the many patients and physicians who partnered with us on       Sovaldi’s clinical studies,” said John C. Martin, PhD, Chairman and       Chief Executive Officer, Gilead Sciences.   
      Sovaldi’s approval is supported primarily by data from four Phase 3       studies, NEUTRINO, FISSION, POSITRON and FUSION, which evaluated 12 or       16 weeks of treatment with Sovaldi combined with either RBV or RBV plus       peg-IFN. Three of these studies evaluated Sovaldi plus RBV in genotype 2       or 3 patients who were either treatment-naïve (FISSION),       treatment-experienced (FUSION) or peg-IFN intolerant, ineligible or       unwilling (POSITRON). NEUTRINO evaluated Sovaldi in combination with       Peg-IFN/RBV in treatment naïve patients with genotypes 1, 4, 5 or 6. In       these studies, Sovaldi-based therapy was found to be superior to       historical controls (NEUTRINO and FUSION) or to placebo (POSITRON), or       non-inferior to currently available treatment options (FISSION) based on       the proportion of patients who had a sustained virologic response (HCV       undetectable) 12 weeks after completing therapy (SVR12). Patients who       achieve SVR12 are considered cured of HCV. Trial participants taking       Sovaldi-based therapy achieved SVR12 rates of 50-90 percent. For full       study details, see the Clinical Studies section of the full Prescribing       Information.   
      During the FDA’s review, data from two additional Phase 3 studies,       VALENCE and PHOTON-1, were added to the NDA as a result of the       Breakthrough Designation status. In the VALENCE study, patients with       genotype 3 HCV infection were treated with Sovaldi and RBV for 24 weeks.       Eighty-four percent of patients in this trial achieved SVR12. The       PHOTON-1 study evaluated Sovaldi and RBV for 12 weeks in patients with       genotype 2 HCV infection co-infected with HIV-1 and for 24 weeks in       patients with genotypes 1 or 3 HCV co-infected with HIV-1. Trial       participants achieved SVR12 rates of 76-92 percent. In all Phase 3       studies of Sovaldi, no viral resistance to the drug was detected among       patients who relapsed following completion of therapy.   
      To date, nearly 3,000 patients have received at least one dose of       Sovaldi in Phase 2 or 3 studies. Sovaldi combination therapy was well       tolerated in clinical studies. Adverse events were generally mild and       there were few treatment discontinuations due to adverse events. The       most common adverse events occurring in at least 20 percent of patients       receiving Sovaldi in combination with Peg-IFN/RBV were fatigue,       headache, nausea, insomnia and anemia; see below for Important Safety       Information regarding contraindications, warnings and precautions,       adverse reactions and drug interactions.   
      On November 22, 2013, the Committee for Medicinal Products for Human Use       (CHMP) of the European Medicines Agency (EMA) issued a positive opinion       on Gilead’s application for marketing authorization for Sovaldi. The       CHMP opinion was adopted following an accelerated review procedure,       which is reserved for medicinal products that are expected to be of       major public health interest. This assessment does not guarantee       marketing authorization by the European Commission. If approved, Sovaldi       could be available in the European Union in the first quarter of 2014.       Applications for marketing approval of Sovaldi are also pending in       Australia, Canada, New Zealand, Switzerland and Turkey.   
      Dr. Jacobson is a paid consultant to Gilead.   
      The Wholesaler Acquisition Cost (WAC) of a 28-tablet bottle of Sovaldi       in the United States is $28,000.   
      U.S. Patient Assistance Program   
      Gilead is committed to ensuring that people with hepatitis C can access       Sovaldi and has launched Support Path™ (www.MySupportPath.com)       to provide assistance to patients who are uninsured, underinsured or who       need financial assistance to pay for the medicine. The program consists       of an integrated offering of support services for patients and       providers, including:   
   

•         Access to dedicated case managers to help patients and their providers         with insurance-related needs, including identifying alternative         coverage options such as federally-insured programs (e.g., Medicaid,         Medicare) and health exchanges.
•         Education and support, including a 24/7 nursing support service line         and the ability to schedule an onsite visit from a clinical educator.
•         The Sovaldi Co-pay Coupon Program, which provides co-pay assistance         for eligible patients with private insurance who need assistance         paying for out-of-pocket medication costs. Most patients will pay no         more than $5 per co-pay. Co-pay assistance can also be applied toward         deductibles and co-insurance obligations.
•         Gilead will provide support to the Patient Access Network (PAN)         Foundation, an independent non-profit organization that provides         assistance for eligible federally-insured and privately-insured         patients who need help covering out-of-pocket medication costs.
•         The Support Path Patient Assistance Program will provide Sovaldi at no         charge for eligible patients with no other insurance options.
  

      Information about how to apply for any of these forms of assistance can       be found at www.MySupportPath.com       or by calling 1-855-7MyPath (1-855-769-7284) between 9 a.m. - 8 p.m. EST.   
      Global Availability   
      Gilead is committed to helping ensure access to Sovaldi in       resource-limited settings. The company is developing a hepatitis C       treatment access program, focusing on those countries with the greatest       HCV burden. Full program details will be announced in the coming months.   
      About Sovaldi   
      Sovaldi is an oral nucleotide analog inhibitor of the HCV NS5B       polymerase enzyme, which plays an essential role in HCV replication.       Sovaldi is a direct-acting agent, meaning that it interferes directly       with the HCV life cycle by suppressing viral replication. Treatment       regimen and duration for Sovaldi are dependent on both viral genotype       and patient population. Treatment response varies based on baseline host       and viral factors. Monotherapy is not recommended for treatment of CHC.   
      Note to editors: Additional multimedia and information can be found       at http://smp.businesswire.com/pages/fda-approves-sovaldi-sofosbuvir-400-mg-tablets-treatment-chronic-hepatitis.   
      IMPORTANT SAFETY INFORMATION   
      Contraindications   
      Sovaldi combination treatment with ribavirin or with peginterferon alfa       plus ribavirin is contraindicated in women who are pregnant or may       become pregnant and men whose female partners are pregnant because of       the risk for birth defects and fetal death associated with ribavirin.       Contraindications to peginterferon alfa and ribavirin also apply to       Sovaldi combination treatment. Refer to the prescribing information of       peginterferon alfa and ribavirin for a list of their contraindications.   
      Warnings and Precautions   
   

•         Pregnancy: Use with Ribavirin or Peginterferon Alfa/Ribavirin: Ribavirin         therapy should not be started unless a report of a negative pregnancy         test has been obtained immediately prior to initiation of therapy.         Female patients of childbearing potential and their male partners must         use two forms of non-hormonal contraception during treatment and for         at least 6 months after treatment has concluded. Routine monthly         pregnancy tests must be performed during this time. Refer to the         prescribing information for ribavirin.
•         Use with Potent P-gp Inducers: Rifampin and St. John’s wort         should not be used with Sovaldi as they may significantly decrease         sofosbuvir plasma concentration, reducing its therapeutic effect.
  

      Adverse Reactions   
      Most common (≥20%, all grades) adverse reactions for:   
   

•         Sovaldi + peginterferon alfa + ribavirin combination therapy were         fatigue, headache, nausea, insomnia, and anemia
•         Sovaldi + ribavirin combination therapy were fatigue, and headache
  

      Drug Interactions   
      In addition to rifampin and St. John’s wort, coadministration of Sovaldi       is not recommended with carbamazepine, oxcarbazepine, phenobarbital,       phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such       coadministration is expected to decrease the concentration of       sofosbuvir, reducing its therapeutic effect.   

StephenW

www.natap.org

美国食品和药物管理局批准Gilead公司的Sovaldi （ TM ） （ Sofosbuvir ）治疗慢性丙型肝炎的治疗
美国食品和药物管理局批准Gilead公司的Sovaldi ™ （ Sofosbuvir ）治疗慢性丙型肝炎的治疗

- Sovaldi在基因型1 ， 2 ， 3或4批准的用途 -

- 高的治愈率（ SVR12 ）缩短，治疗12周的课程为许多患者 -

- 第一次口服治疗方案基因型2或3 -

- 第一次治疗的患者等待肝移植预防HCV复发 -



福斯特城，加利福尼亚州 - （美国商业资讯） - 吉利德科学公司（Nasdaq ： GILD ）今天宣布，美国食品和药物管理局（FDA ）已批准Sovaldi ™ （ sofosbuvir ） 400毫克片剂，每日一次口服核苷酸类似物聚合酶抑制剂，用于治疗慢性丙型肝炎（CHC）感染的治疗中作为一个组合的抗病毒治疗方案的组成部分。 Sovaldi的功效已经建立的受试者的丙型肝炎病毒（HCV）基因型1，2， 3或4感染，包括那些与肝细胞癌会议Milan标准（等待肝移植）和那些与HCV/HIV-1共同感染。推荐治疗方案和治疗时间为Sovaldi联合治疗丙型肝炎病毒单感染或HCV/HIV-1合并感染的患者如下：

    “在临床研究中， Sovaldi与其他药剂组合来实现非常高的治愈率，缩短治疗时间，以少至12周，减少或完全省去了干扰素注射剂，根据不同的病毒基因型。 ”

  治疗持续时间
基因型1或4      Sovaldi + PEG -干扰素α+利巴韦林  12周
基因型2           Sovaldi +利巴韦林   12周
基因型3           Sovaldi +利巴韦林   24周


Sovaldi与利巴韦林联合治疗24周可以考虑CHC患者的基因型1感染谁是干扰素不合格。此外， Sovaldi应使用与利巴韦林联合治疗CHC肝癌患者等待肝移植48周或直到肝移植，以防止移植后HCV感染的。治疗方案，持续时间和响应Sovaldi依赖于病毒基因型和患者人群，以及相关的基线因素。单药治疗不推荐使用。完整处方信息将可在www.Gilead.com 。

美国食品药物管理局批准Sovaldi优先审核和突破疗法称号，这是给予研究药物可能提供重大进展的治疗比现有的方案。

“我相信， Sovaldi将不得不显著提高谁是治愈丙肝的美国人的数量对公共健康产生重大影响， ”艾拉·雅各布森博士胃肠病学和肝病学杂志，威尔康乃尔医学院，纽约分部的首席说市和Sovaldi临床试验的主要研究者。 “在临床研究中， Sovaldi与其他药剂组合来实现非常高的治愈率，缩短治疗时间，以少至12周，减少或完全省去了干扰素注射剂，根据不同的病毒基因型。 ”

慢性丙型肝炎影响了大约400万人在美国，其中大部分是“婴儿潮” -  1945年和1965年之间出生的人。本病是肝癌和肝移植的全国领先的原因，并在最近几年已经超越了艾滋病毒/艾滋病死亡的原因。关心的用于HCV的当前标准涉及多达48个星期的治疗用聚乙二醇化干扰素（ PEG-IFN ） /利巴韦林（ RBV）的含方案，这可能不适合于某些类型的患者。

“这是我们的希望， Sovaldi将标志着在丙型肝炎治疗的一个新时代的开始。基列是自豪地发挥在实现这一重要的治疗进展，我们希望我们的感谢延伸到许多患者和医生谁与我们合作的Sovaldi的临床研究中的作用，说：“约翰·C ·马丁博士，董事长兼首席总裁，吉利德科学。

Sovaldi的认可主要是由来自四个阶段的数据支持3项研究，中微子，裂变，正电子和融合，从而评估了12或16周， Sovaldi治疗结合两种或利巴韦林利巴韦林加PEG-IFN的。这三个研究评估Sovaldi加利巴韦林在基因型2或3的病人谁要么治疗初治（裂变） ，处理有经验的（融合）或PEG-IFN不能耐受，无资格或不愿意（正电子） 。中微子评估Sovaldi与PEG-IFN/RBV联合治疗初治患者的基因型1 ， 4 ， 5或6 。在这些研究中， Sovaldi为基础的治疗被认为是目前可用的治疗方案（裂变）的基础上谁的病人有持续的比例优于历史对照（中微子和融合）或安慰剂（正电子） ，或者非劣病毒学应答（ HCV检测不到）完成治疗（ SVR12 ）后12周。患者谁达到SVR12被认为是治愈丙型肝炎病毒。受试者服用Sovaldi为基础的治疗取得了50-90 ％的SVR12费率。为充分研究的详细信息，请参阅完整的处方信息的临床研究部分。

在FDA的审查，从另外两个阶段的数据3项研究，价态和光子- 1 ，分别加入新发展区作为突破口指定状态的结果。在价的研究中，患者的基因3型HCV感染与Sovaldi和RBV治疗24周。患者在本试验中百分之八十四达到SVR12 。光子- 1研究评估Sovaldi和RBV治疗12周的患者2型HCV感染合并感染HIV-1和24周患者的基因型1或3 HCV合并感染HIV - 1 。试验参与者达到了76-92 ％的SVR12费率。在Sovaldi所有3阶段研究，无病毒对药物产生抗药性之间谁复发以下完成治疗的患者进行检测。

迄今为止，已有近3000名患者已收到Sovaldi的至少一个剂量在第2阶段和3项研究。 Sovaldi联合治疗耐受性良好，在临床研究中。不良反应一般轻微，有因不良反应少的治疗终止。在至少20 ％的接受Sovaldi与PEG-IFN/RBV结合患者发生的最常见的不良反应有乏力，头痛，恶心，失眠和贫血;见下面的重要安全信息有关的禁忌症，警告和注意事项，不良反应和药物相互作用。

于2013年11月22日，欧洲药品管理局（EMA ）的医药产品委员会为人力使用（CHMP ）发行Gilead公司的申请，对Sovaldi营销授权一个积极的意见。下一个加速审查程序，这是保留给那些有望成为重大的公共卫生利益的药品的CHMP的意见被采纳。这一评估并不由欧盟委员会保证市场授权。如果获得批准， Sovaldi可能取得欧盟在2014年第一季度。申请Sovaldi的销售许可也正在申请在澳大利亚，加拿大，新西兰，瑞士和土耳其。

雅各布森博士是支付顾问基列。

28片剂瓶Sovaldi在美国的批发商收购成本（ WAC ）为28,000元。

美患者援助计划

Gilead公司致力于确保人们与丙型肝炎可以访问Sovaldi并已推出支持路径™ （ www.MySupportPath.com ）提供援助，以病人谁是保险，保险不足或谁需要财政援助，以支付医药。该计划包括支持服务的患者和提供一个集成的产品，其中包括：

    访问专用的个案经理，以帮助患者和他们的供应商与保险有关的需求，包括确定替代覆盖选项，如联邦保险的方案（例如，医疗补助，医疗保险）和卫生交流。
    教育和支持，包括一个24/7的护理支持服务专线，并从临床教育家安排进行实地访查的能力。
    该Sovaldi共付优惠券项目，它提供了符合条件的患者有私人保险谁需要帮助支付了自付药费共付援助。大多数患者将支付不超过5美元共付额。共付援助，也可以对免赔额和共同保险义务的适用。
    吉利德将提供支持，以病人接入网络（ PAN）的基金会，一个独立的非营利组织，提供援助资格联邦政府保险和私人保险的病人谁需要帮助，涵盖了自付药费。
    支持路径患者援助计划将提供Sovaldi在不收费的符合条件的患者没有其他保险的选择。

晚上8点EST  - 关于如何申请上述任何形式的援助信息，可www.MySupportPath.com或致电1 -855- 7MyPath （ 1-855-769-7284 ）上午9时之间被发现。

全球可用性

吉利德致力于帮助确保获得Sovaldi在资源有限的环境。该公司正在开发一种丙型肝炎治疗的访问计划，重点对这些国家以最大的丙型肝炎病毒的负担。完整的程序细节将在未来几个月内公布。

关于Sovaldi

Sovaldi是丙型肝炎病毒NS5B聚合酶的酶，它在HCV的复制中发挥核心作用的口服核苷酸类似物抑制剂。 Sovaldi是一种直接作用剂，也就是说，它会干扰直接与HCV生命周期中通过抑制病毒复制。治疗方案和持续时间Sovaldi依赖于这两个病毒的基因型和患者人群。基于基线宿主和病毒因素对治疗的反应各不相同。单药治疗不推荐用于治疗慢性丙型肝炎。

编者注：其他多媒体和信息可以在这里找到

重要安全信息

禁忌

与利巴韦林或聚乙二醇干扰素α联合利巴韦林Sovaldi联合治疗是禁忌的妇女谁是怀孕或可能会因为与利巴韦林相关的出生缺陷和胎儿死亡的风险的孕妇和人，他们的女性伴侣怀孕。禁忌症对聚乙二醇干扰素α和利巴韦林也适用于Sovaldi联合治疗。请参阅聚乙二醇干扰素α和利巴韦林的处方信息，他们的禁忌列表。

警告和注意事项

    妊娠：使用利巴韦林或聚乙二醇干扰素α /利巴韦林：利巴韦林治疗不应该被启动，除非一个妊娠试验阴性的报告已经前已开始治疗获得。生育潜力和她们的男性伴侣的女性患者必须使用两种形式的非激素避孕期间的治疗和至少6个月后的治疗已经结束。例行月度妊娠试验必须在这段时间内进行。请参考利巴韦林处方信息。
    使用具有强效P-gp的诱导剂：利福平和圣约翰草不应该与Sovaldi使用，因为它们可能会显著降低sofosbuvir血药浓度，降低其治疗效果。

不良反应

最常见（ ≥ 20 ％ ，所有级别）的不良反应为：

    Sovaldi +聚乙二醇干扰素α +利巴韦林联合治疗有乏力，头痛，恶心，失眠，贫血
    Sovaldi +利巴韦林联合治疗有乏力，头痛等症状

药物相互作用

除了利福平和圣约翰草， Sovaldi合用，不建议用卡马西平，奥卡西平，苯巴比妥，苯妥英钠，利福布丁，利福喷丁，和替拉那韦/利托那韦。这样的共同给药预计降低sofosbuvir的浓度，从而降低其疗效。