2014年12月19日，美国食品药品监督管理局（以下简称FDA）批准Viekira Pak（ombitasvir+ paritaprevir+ ritonavir片剂联合dasabuvir片剂）用于治疗基因1型慢性丙型肝炎病毒（HCV）感染者，包括合并肝硬化的患者。
丙肝是一种引起肝脏炎症的病毒性疾病，可导致肝功能下降、肝功能衰竭或肝癌。大多感染丙肝病毒的患者在出现明显肝损害前没有任何症状，这一潜伏期可达数十年。据美国疾病控制与预防中心（CDC）的数据显示，美国约有320万人感染HCV，如果得不到适当治疗，其中将有15%～30%的感染者会发展成肝硬化。
Viekira Pak包含三种新药——ombitasvir、paritaprevir和dasabuvir，这三种药物可协同抑制丙肝病毒的生长。Viekira Pak还包含了之前获批用于增加血中paritaprevir浓度的药物——ritonavir。Viekira Pak可以和利巴韦林联合使用，也可以单独使用，但是不推荐失代偿期肝硬化的患者使用。
“新一代的丙肝病毒治疗学正在改变美国丙肝患者的治疗模式，”FDA药物评价和研究中心抗菌产品办公室主任Edward Cox博士说。“我们看到口服新药的持续发展，相比以干扰素为基础的老一代治疗方案，这些新药不仅有非常高的病毒学应答率，而且更加安全。”
Viekira Pak是在过去一年里获得FDA批准、用于治疗慢性HCV感染的第四个药物。FDA于2013年11月批准了Olysio（simeprevir），于2013年12月批准了Sovaldi（索菲布韦），于2014年10月批准了Harvoni（来地帕韦+索菲布韦）。
Viekira Pak的有效性在六个临床实验中得到评估，这些试验总共入组了2308名受试者，他们是患有肝硬化和无肝硬化的慢性HCV感染者。在不同的试验中，受试者随机接受Viekira Pak治疗或安慰剂（糖衣药片）治疗；Viekira Pak联合或不联合利巴韦林治疗； Viekira Pak联合利巴韦林治疗12周或24周。
这些试验旨在确定，受试者在治疗结束至少12周后血液中是否还能检测到丙肝病毒（持续病毒学应答，或SVR），SVR用以表明患者的丙肝已经治愈。包括难治性患者在内的多种受试者群体的试验结果显示，在接受Viekira Pak推荐剂量治疗的受试者中，有91%～100%的受试者实现了持续病毒学应答。Viekira Pak的推荐剂量是12.5mg ombitasvir + 75mg paritaprevir + 50mg ritonavir片剂，一天一次，一次2片；和250mg dasabuvir片剂，一天两次，一次1片。
临床试验受试者中最常见的副作用是疲惫、瘙痒、虚弱无力或缺乏活力、恶心和睡眠困难。
Viekira Pak是第11个获得FDA突破性疗法认定并获得批准的新药。FDA将某一药物认定为突破性疗法的条件如下：申办方提出申请，且初步临床证据表明申请药物在严重或危及生命的疾病治疗中可能明显优于现有治疗。FDA经优先评审程序对Viekira Pak进行了审批。优先评审程序用于批准治疗重大疾病的药物，若获得批准，这些药物会显著优于现有上市药物的安全性或有效性。
Viekira Pak由总部设在伊利诺伊州北芝加哥的艾伯维公司推广。Olysio由总部设在新泽西州的力登公司推广。Sovaldi和Harvoni由总部设在加州福斯特市的吉利德科学公司推广。

European Commission Grants Marketing Authorizations for AbbVie's VIEKIRAX® (ombitasvir/paritaprevir/ritonavir tablets) + EXVIERA® (dasabuvir tablets) for the Treatment of Chronic Hepatitis C
- In Phase 3 clinical trials, VIEKIRAX + EXVIERA cured 95-100 percent of genotype 1 chronic hepatitis C patients, with less than 2 percent of patients experiencing virologic failure[1],[2]
- Tolerability profile shows more than 98 percent of patients completed a full course of therapy[3]
- All-oral, interferon-free regimen also approved for HCV/HIV-1 co-infection, patients on opioid substitution therapy and patients who have undergone a liver transplant[1],[2]
- VIEKIRAX + EXVIERA are the first products to be approved as a combination treatment of three direct-acting antivirals with distinct mechanisms of action targeting hepatitis C at multiple steps in the viral lifecycle[1],[2]
NORTH CHICAGO, Ill., Jan. 16, 2015 /PRNewswire/ -- AbbVie (NYSE: ABBV) announced that the European Commission has granted marketing authorizations for its all-oral, short-course, interferon-free treatment of VIEKIRAX® (ombitasvir/paritaprevir/ritonavir tablets) + EXVIERA® (dasabuvir tablets).1,2 The treatment has been approved with or without ribavirin (RBV) for patients with genotype 1 (GT1) chronic hepatitis C virus (HCV) infection, including those with compensated liver cirrhosis, HIV-1 co-infection, patients on opioid substitution therapy and liver transplant recipients.1,2 Additionally, VIEKIRAX has been approved for use with RBV in genotype 4 (GT4) chronic hepatitis C patients.1
"The approval of AbbVie's hepatitis C treatment in the European Union, following the recent approvals in the U.S. and Canada, offers patients across Europe a new and effective treatment to cure this serious disease," said Richard Gonzalez, chairman of the board and chief executive officer, AbbVie. "We are committed to working with local governments and healthcare systems to support broad access to VIEKIRAX + EXVIERA." 
The approvals follow a review under accelerated assessment by the European Medicines Agency, designated to new medicines of major public health interest. Approximately nine million people in Europe are infected with chronic hepatitis C, a major cause of liver cancer and liver transplantation.4 Genotype 1 is the most prevalent form of hepatitis C in Europe, accounting for 60 percent of cases worldwide.5 In Europe, the most prevalent sub-genotype is 1b (47 percent).6 Genotype 4, most common in the Middle East, sub-Saharan Africa and Egypt, is becoming increasingly prevalent in several European countries, including Italy, France, Greece and Spain.7 AbbVie's treatment is now licensed for use in all 28 member countries of the European Union, as well as in the U.S., Canada, Switzerland, Iceland, Liechtenstein and Norway.
"Hepatitis C is a complex disease, with multiple genotypes and special patient populations that need to be considered when determining the right treatment for an individual patient," said Stefan Zeuzem, M.D., professor of medicine and chief of the department of medicine I, J.W. Goethe University Hospital, Frankfurt, Germany. "In clinical trials, AbbVie's treatment achieved high cure rates with low rates of discontinuation across a variety of patient populations, making it an important addition to the class of therapies that is changing the way hepatitis C is being treated."
Treating hepatitis C is complex because the virus mutates and replicates rapidly. VIEKIRAX + EXVIERA are the first products to be approved as a combination treatment of three direct-acting antivirals with distinct mechanisms of action and non-overlapping resistance profiles to target hepatitis C at multiple steps in the viral lifecycle.1,2
"With the approval of VIEKIRAX + EXVIERA in the European Union, we are offering a treatment that achieved high cure rates for people living with GT1 and GT4 chronic hepatitis C," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "This is an important part of our ongoing commitment to advancing public health by applying innovative science to the development of promising medicines."
Robust Clinical Development Program
The approval of VIEKIRAX + EXVIERA is supported by a robust clinical development program designed to study the safety and efficacy of the regimen in more than 2,300 enrolled patients across 25 countries.1,2 The program consisted of six pivotal Phase 3 studies, which demonstrated that VIEKIRAX + EXVIERA cured 95-100 percent of hepatitis C patients with GT1 HCV infection who received the recommended regimen, with less than 2 percent of patients experiencing virologic failure.1,2 Additionally, more than 98 percent (n=2,011/2,053) of patients in clinical trials completed a full course of therapy.3 Most common (>20 percent) adverse reactions for VIEKIRAX + EXVIERA with RBV were fatigue and nausea.1,2
The approval of VIEKIRAX + EXVIERA is also based on the results from Phase 2 clinical trials in GT1 chronic HCV infected patients, which showed that VIEKIRAX + EXVIERA cured 97 percent (n=33/34) of liver transplant recipients, 92 percent (n=58/63) of patients co-infected with HIV-1 and 97 percent (n=37/38) of patients on opioid substitution therapy.1,2 Patients who achieve a sustained virologic response (SVR12) are considered cured of hepatitis C.
Approval of VIEKIRAX in GT4 chronic hepatitis C was based on a Phase 2 study in which patients treated with VIEKIRAX with RBV achieved 100 percent SVR12.1
About VIEKIRAX® + EXVIERA®
VIEKIRAX + EXVIERA is approved for the treatment of genotype 1 chronic hepatitis C virus infection, including patients with compensated cirrhosis. VIEKIRAX consists of the fixed-dose combination of paritaprevir 150mg (NS3/4A protease inhibitor) and ritonavir 100mg with ombitasvir 25mg (NS5A inhibitor), dosed once daily, and EXVIERA consists of dasabuvir 250mg (non-nucleoside NS5B polymerase inhibitor) dosed twice daily taken with or without ribavirin, dosed twice daily. VIEKIRAX + EXVIERA is taken for 12 weeks with or without RBV, except in GT1a patients with cirrhosis, who should take it for 24 weeks.
For the treatment of genotype 4 chronic hepatitis C patients, AbbVie's treatment consists of VIEKIRAX dosed once daily taken with RBV, dosed twice daily.
Paritaprevir was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for hepatitis C protease inhibitors and regimens that include protease inhibitors. Paritaprevir has been developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of chronic hepatitis C.
Additional information about AbbVie's hepatitis C development program can be found on www.clinicaltrials.gov.
EU Indication
VIEKIRAX is indicated in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adults. EXVIERA is indicated in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adults.
Important EU Safety Information
Contraindications:
VIEKIRAX + EXVIERA are contraindicated in patients with severe hepatic impairment (Child-Pugh C). Patients taking ethinyl estradiol-containing medicinal products must discontinue them and switch to an alternative method of contraception prior to initiating VIEKIRAX + EXVIERA. Do not give VIEKIRAX with certain drugs that are sensitive CYP3A substrates or strong inhibitors of CYP3A. Do not give VIEKIRAX and EXVIERA with strong or moderate enzyme inducers. Do not give EXVIERA with certain drugs that are strong inhibitors of CYP2C8.
Special warnings and precautions for use:
VIEKIRAX and EXVIERA are not recommended as monotherapy and should be used in combination with other medicinal products for the treatment of hepatitis C infection.
Pregnancy and concomitant use with ribavirin
When VIEKIRAX + EXVIERA are used in combination with ribavirin, women of childbearing potential or their male partners must use an effective form of contraception during the treatment and 6 months after the treatment. Refer to the Summary of Product Characteristics for ribavirin for additional information.
ALT elevations
Transient elevations of ALT to >5x ULN without concomitant elevations of bilirubin occurred in clinical trials with VIEKIRAX + EXVIERA and were more frequent in a subgroup who were using ethinyl estradiol-containing contraceptives.
Use with concomitant medicinal products
Use caution when administering VIEKIRAX with fluticasone or other glucocorticoids that are metabolized by CYP3A4. A reduction in colchicine dosage or interruption in colchicine is recommended in patients with normal renal or hepatic function. VIEKIRAX with or without EXVIERA is expected to increase exposure of statins so certain statins need to be discontinued or dosages reduced. Low dose ritonavir, which is part of VIEKIRAX, may select for PI resistance in HIV co-infected patients without ongoing antiretroviral therapy. HIV co-infected patients without suppressive antiretroviral therapy should not be treated with VIEKIRAX.
Adverse Reactions
Most common (>20 percent) adverse reactions for VIEKIRAX + EXVIERA with RBV were fatigue and nausea.