10日下午，美国FDA毫无悬念地批准了吉利德科学的全口服、一天一次的抗丙肝二联复方Harvoni（复方sofosbuvir和ledipasvir）上市，用于治疗基因1型的丙型肝炎感染。一个12周或8周疗程的Harvoni在美国预定收费分别为94500和63000美元。因为FDA这一决定在投资人预期之内，吉利德股票今天只有小幅上涨至每股106.88美元，增幅1%。

  丙型病毒性肝炎简称丙型肝炎或丙肝，是一种由丙型肝炎病毒（HCV）感染引起的病毒性肝炎。据世界卫生组织统计，全球HCV的感染率约为3%，共约1.8亿人。在美国丙肝患者大约有320万人。HCV感染主要包括免疫介导和HCV直接损伤两种，感染以后导致肝脏发炎以致肝功能下降甚至衰竭，病理表现以肝细胞坏死和淋巴细胞浸润为主。大多数的丙肝患者感染以后很久才发现肝损伤症状。感染20至30年有10%～20%的患者发展为肝硬化，1%-5%患者会因发生肝细胞癌（HCC）死亡。而且肝硬化一旦出现失代偿情况，比如出现黄疸，腹腔积液，静脉曲张破裂出血，肝性脑病等，其生存率会急剧下降。

  Harvoni是吉利德抗丙肝重磅产品Sovaldi（通用名：sofosbuvir）和固定剂量的蛋白酶NS5A抑制剂ledipasvir的复方组合。Harvoni是第一个批准用于治疗基因1型丙肝感染，且不需要联合干扰素或利巴韦林的全口服抗丙肝方案。Harvoni既可以单药使用，也可以和其它口服制剂比如利巴韦林联合使用。

  支持FDA批准Harvoni的关键数据主要来自3个共有1518例患者参与的3期临床实验。这些患者有之前未接受过治疗的（treatment-na？ve），也包括之前接受过治疗但疗效不佳并且含有肝硬化的患者。受试者随机分为Harvoni单药治疗组或和利巴韦林联合用药组。一级观察终点是治疗12周后持续病毒学应答率（SVR12）。结果发现，第一个3期实验有94%的之前未接受过治疗的患者在治疗8周后获得持续病毒学应答，而且疗程延长到12周后持续病毒学应答率增加至96%。第二个含有部分肝硬化患者的3期临床实验在治疗12周后取得99%的持续病毒学应答率。第三个临床实验评价之前接受过治疗但没有应答，并且包括一些肝硬化的患者。经过12和24周的Harvoni治疗分别有94%和99%的患者获得持续病毒学应答。这些实验中最常见的副作用是疲劳和头痛。

  Harvoni获得FDA“优先评审”资格，也是第7个获得“突破性药物”资质的药物。虽然Sovaldi是抗丙肝药物的头号明星，上市后前两个个季度的销售额分别高达23和35亿美元，但Harvoni凭借以上的诱人数据，相信一旦开始销售很快会取代Sovaldi的霸主地位，成为抗丙肝新的标准疗法。甚至部分医生建议一些早期患者等待Harvoni进入药房。

  当然吉利德也不会永远高枕无忧。艾伯维的全口服抗丙肝三联复方预计在今年12月份能获得美国FDA的批准，而且在披露的几个临床实验中平均持续病毒学应答率更高。默克的MK-5172/MK-8742二联复方的二期临床结果也引人注目，甚至部分分析师认为能直追吉利德。无论如何，短期内Harvoni将必定红极一时，年销售峰值有望超过100亿美元。
吉利德二联复方Harvoni获得FDA批准 抗丙肝新金标全口服方案出炉,香港医药国际贸易有限公司独家率先提供全球科研公司。

View the label approved on 10/10/2014 (PDF)¹¹ for HARVONI, NDA no. 205834  
 

U.S. Food and Drug Administration Approves Gilead’s Harvoni® (Ledipasvir/Sofosbuvir), the First Once-Daily Single Tablet Regimen for the Treatment of Genotype 1 Chronic Hepatitis C

-- Harvoni Achieved Cure Rates (SVR12) of 94-99 Percent in Three Phase 3 Studies --

-- Shortens Treatment Duration to Just Eight Weeks for Certain Treatment-Naïve Patients --

-- Eliminates Need for Interferon and Ribavirin for Patients with Genotype 1 Hepatitis C --

FOSTER CITY, Calif.--(BUSINESS WIRE)--Oct. 10, 2014-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the U.S. Food and Drug Administration (FDA) has approved Harvoni^® (ledipasvir 90 mg/sofosbuvir 400 mg), the first once-daily single tablet regimen for the treatment of chronic hepatitis C genotype 1 infection in adults. Harvoni combines the NS5A inhibitor ledipasvir with the nucleotide analog polymerase inhibitor sofosbuvir, approved under the tradename Sovaldi^® in December 2013. Harvoni’s efficacy has been established in patients with chronic hepatitis C virus (HCV) genotype 1 infection, with a treatment duration of eight, 12 or 24 weeks depending on prior treatment history, cirrhosis status and baseline viral load. Eight weeks of treatment with Harvoni can be considered for treatment-naïve patients without cirrhosis who have baseline HCV viral load below 6 million IU/mL.

Harvoni Product Photo

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The FDA granted Harvoni a Priority Review and Breakthrough Therapy designation, which is given to investigational medicines that may offer major advances in treatment over available therapies.

“By providing very high cure rates in as little as eight weeks and completely eliminating the need for interferon and ribavirin, which are challenging to take and tolerate, Harvoni significantly advances treatment for patients with the most common form of hepatitis C in the United States,” said Nezam Afdhal, MD, Director of Hepatology at Beth Israel Deaconess Medical Center, Professor of Medicine at Harvard Medical School and a principal investigator in the Harvoni clinical trials. “For the first time, the vast majority of patients can be cured with a once-daily pill in only eight or 12 weeks.”

Harvoni’s approval is supported by data from three Phase 3 studies, ION-1, ION-2 and ION-3. These studies eva luated eight, 12 or 24 weeks of treatment with Harvoni, with or without ribavirin, among nearly 2,000 genotype 1 HCV patients with compensated liver disease. These studies included non-cirrhotic treatment-naïve patients (ION-3), cirrhotic and non-cirrhotic treatment-naïve patients (ION-1) and cirrhotic and non-cirrhotic patients who failed prior therapy with an interferon-based regimen, including regimens containing an HCV protease inhibitor (ION-2). The primary endpoint for each study was sustained virologic response (HCV undetectable) 12 weeks after completing therapy (SVR12).

Patients who achieve SVR12 are considered cured of HCV. In these studies, ribavirin was not shown to increase response rates. Trial participants in the ribavirin-free arms (n=863) achieved SVR12 rates of 94 to 99 percent.

“Unlike other serious chronic diseases, hepatitis C can be cured and Harvoni offers patients the potential for a cure in as little as eight weeks,” said John C. Martin, PhD, Chairman and Chief Executive Officer, Gilead Sciences. “Gilead is proud to have played a role in developing a once-daily therapy that is safe, simple and well tolerated. We are now working to ensure rapid and broad access to Harvoni.”

Important Safety Information regarding warnings and precautions, adverse reactions and drug interactions is listed below. Zero percent, less than 1 percent and 1 percent of patients treated for eight, 12 and 24 weeks, respectively, discontinued treatment due to adverse events and fewer adverse events were observed in the ribavirin-free arms compared to the ribavirin-containing arms in all ION studies. The most common adverse reactions among patients treated with Harvoni (≥5 percent) were fatigue, headache, nausea, diarrhea and insomnia. For additional study details, and complete dosing information, see the Clinical Studies and Dosage and Administration sections, respectively, of the full Prescribing Information.

U.S. Patient Support Program
To assist eligible hepatitis C patients in the United States with access to Harvoni, Gilead has added the medicine to its Support Path™ (www.MySupportPath.com) program. The program consists of an integrated offering of support services for patients and providers, among them:

• Call center staffed with associates trained to help patients and their providers with insurance-related needs.
• Education and support, including a 24/7 nursing support service line.
• The Harvoni and Sovaldi Co-pay Coupon Programs, which provide 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.
• The Support Path Patient Assistance Program, which will provide Harvoni and Sovaldi at no charge for eligible patients with no other insurance options.

Gilead also provides support to independent non-profit organizations that provide assistance for eligible federally-insured and privately-insured patients who need help covering out-of-pocket medication costs.

To learn more about Support Path for Harvoni or Sovaldi, please visit www.MySupportPath.com or call 1-855-769-7284 between 9:00 a.m. – 8:00 p.m. Eastern, Monday through Friday.

IMPORTANT SAFETY INFORMATION
Warnings and Precautions
Risk of Reduced Therapeutic Effect of Harvoni Due to P-gp Inducers: Rifampin and St. John’s wort are not recommended for use with Harvoni as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.

Related Products Not Recommended: Harvoni is not recommended for use with other products containing sofosbuvir (Sovaldi).

Adverse Reactions
Most common (≥10%, all grades) adverse reactions were fatigue and headache.

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

Coadministration of Harvoni is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.

Consult the full Prescribing Information for Harvoni for more information on potentially significant drug interactions, including clinical comments.

About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North and South America, Europe and Asia Pacific.

Forward-Looking Statement
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that physicians and patients may not see advantages of Harvoni over other therapies and may therefore be reluctant to prescribe the product, and the risk that private and public payers may be reluctant to provide coverage or reimbursement for the product. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2014, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

U.S. Full Prescribing Information for Harvoni and Sovaldi is available at www.gilead.com.

Harvoni, Sovaldi and Support Path are trademarks or registered trademarks of Gilead Sciences, Inc., or its related companies.

For more information on Gilead Sciences, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

Photos/Multimedia Gallery Available: http://www.businesswire.com/multimedia/home/20141010005587/en/

Source: Gilead Sciences, Inc.

Gilead Sciences, Inc.
Patrick O’Brien, Investors, 650-522-1936
Cara Miller, Media, 650-522-1616

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