首个丙肝一日一次缓释剂新药VIEKIRA XR缓释片获FDA批准上市
近日，生物制药公司艾伯维（AbbVie）宣布，美国FDA已经批准了其产品VIEKIRA XR缓释片的新药申请（NDA）。 VIEKIRA XR是每日一次的缓释制剂，与先前获批产品VIEKIRA PAK一样，有效成分是dasabuvir、ombitasvir、paritaprevir和ritonavir，用于治疗基因1型的慢性丙型肝炎病毒成人感染者。他们包括伴有代偿性肝硬化的患者，但不包括那些晚期肝硬化伴有失代偿性肝硬化的丙肝患者。
丙型肝炎是一种由于丙型肝炎病毒感染而引起的肝脏炎症疾病，它可导致肝功能下降、肝衰竭甚至肝癌。据美国CDC统计，大约有270万美国人感染有丙型肝炎病毒。根据世界卫生组织的数据，全球估计有1.7亿人患有慢性丙型肝炎，每年有大约有50万人死于与丙肝相关的肝脏疾病。大多数感染有丙型肝炎病毒的人在肝脏损伤变得明显之前没有疾病症状，如果不进行正常治疗，这一感染过程在20到30年后，其中有10-20%的患者个体会发展为肝硬化和肝癌。目前，尚无预防丙型肝炎病毒感染的疫苗。
丙肝病毒有六种不同的基因型，不同的基因型对药物反应也不同。其中1型是最常见的丙肝亚型，约占60%。以往丙肝的治疗方法以干扰素和利巴韦林（Ribavirin）为基础，需要每周静脉注射，经48周疗程后，治愈率仍只有50％左右。
VIEKIRA XR是一个由200毫克dasabuvir、8.33毫克ombitasvir、50毫克paritaprevir和33.33毫克ritonavir组合的缓释片剂，每日一次给药三粒，必须与食物一起服用。
FDA对VIEKIRA XR的批准是基于七个3期临床试验的良好数据，2300多名患者接受VIEKIRA PAK治疗后有非常高的治愈率。同时，VIEKIRA XR也通过了与VIEKIRA PAK比较的两项生物制剂等效性试验。
艾伯维的副总裁兼首席医疗官Rob Scott博士说道：“艾伯维致力于继续推动丙型肝炎的治疗护理，这是我们对患者持续承诺的积极表现。VIEKIRA XR的成分被临床试验数据证明针对基因1b型患者有100％的治愈率，VIEKIRA XR的新药申请获批为1型丙肝患者提供了新的治疗选择方案。”
批准日期：2016年8月6日  公司：AbbVie Inc
VIEKIRA XR（达沙布韦/替勃韦韦/帕瑞普韦/利托那韦[dasabuvir/ombitasvir/paritaprevir/ritonavir]）缓释片，用于口服
美国初步批准：2014年
作用机制
VIEKIRA XR结合了三种直接作用的丙型肝炎病毒抗病毒剂和不同的作用机制[参见微生物学]。
利托那韦对HCV无活性。 利托那韦是一种有效的CYP3A抑制剂，其增加了帕利匹韦的峰和谷血浆药物浓度和总体药物暴露（即，曲线下面积）。
适应症和用法
VIEKIRA XR包括达沙布韦，丙型肝炎病毒非核苷NS5B棕榈聚合酶抑制剂ombitasvir，丙型肝炎病毒NS5A抑制剂，paritaprevir，丙型肝炎病毒NS3 /4A蛋白酶抑制剂和利托那韦，CYP3A抑制剂，用于治疗的慢性丙型肝炎病毒（HCV）成人患者：
基因型1b感染无肝硬化或与补偿性肝硬化
无肝硬化的基因型1a感染或与利巴韦林组合使用的补偿性肝硬化。
剂量和给药
开始前的测试 - 评估肝脏失代偿的实验室和临床证据。
推荐剂量：每天服用三片。 VIEKIRA XR必须服用，因为在禁食条件下给药可能导致减少的病毒学应答和可能的抗药性发展。
治疗方案和患者人群的持续时间患者人群治疗*持续时间
基因型1a，
无肝硬化VIEKIRA XR +利巴韦林12周
基因型1a，
与补偿性肝硬化VIEKIRA XR +利巴韦林24周**
基因型1b，
有或无补偿性肝硬化VIEKIRA XR 12周
*注意：遵循基因型1a给药建议在未知基因型1亚型或混合基因型1感染的患者。
基于以前的治疗史，一些患者可考虑使用VIEKIRA XR与利巴韦林联合给药12周[参见临床研究]。
HCV/HIV-1共感染：对于HCV/HIV-1共感染的患者，遵循上表中的剂量建议。
肝移植受者：在肝移植受者肝功能正常和轻度纤维化（Metavir纤维化评分≤2），VIEKIRA XR与利巴韦林的推荐的持续时间是24周。
剂量形式和强度
缓释片：200mg达沙布韦，8.33mg替勃韦韦，50mg帕瑞普韦和33.33mg利托那韦
禁忌症
中重度肝损伤患者。
如果VIEKIRA XR与利巴韦林一起施用，那么利巴韦林的禁忌症也适用于该组合方案。
与以下药物的共同给药：高度依赖于CYP3A用于清除;中度或强的CYP3A诱导剂或强的CYP2C8诱导剂;和CYP2C8的强抑制剂。
已知对利托那韦的超敏反应（例如中毒性表皮坏死松解，史蒂文斯 - 约翰逊综合征）。
警告和注意事项
肝硬化患者肝功能衰竭和肝功能衰竭：肝功能失代偿和肝功能衰竭，包括肝移植或致死性结果，主要报告在晚期肝硬化患者中。监测肝失代偿的临床体征和症状。
ALT立面：在开始VIEKIRA XR之前停止含炔雌醇的药物（推荐替代避孕方法）。在治疗的前4周对所有患者进行肝实验室检查。对于VIEKIRA XR的ALT升高，密切监测并遵循完全处方信息中的建议。
与利巴韦林联合治疗相关的风险：如果VIEKIRA XR与利巴韦林一起施用，则利巴韦林的警告和注意事项也适用于该组合方案。
药物相互作用：VIEKIRA XR和某些其它药物的伴随使用可能导致已知的或潜在显着的药物相互作用，其中一些可能导致VIEKIRA XR的治疗效果的丧失。
不良反应
在接受达沙布韦与替比夫韦，帕利匹韦，利托那韦和利巴韦林组合的受试者中，最常见的不良反应（大于10％的受试者）是疲劳，恶心，瘙痒，其他皮肤反应，失眠和虚弱。在接受达沙布韦与替比夫韦，帕利匹韦，利托那韦无利巴韦林组合的受试者中，最常报道的不良反应（大于或等于受试者的5％）是恶心，瘙痒和失眠。
药物相互作用
VIEKIRA XR的共同给药可以改变一些药物的血浆浓度，一些药物可以改变VIEKIRA XR的血浆浓度。在治疗之前和治疗期间必须考虑药物相互作用的可能性。在治疗之前和治疗期间咨询完整的处方信息，以了解潜在的药物相互作用。
如何供应/存储和处理
VIEKIRA XR每月分装一次，共28天治疗。 每月每箱包含四个每周纸箱。 每个每周纸盒包含七个每日剂量包。
每个耐儿童日剂量包装含有三片片剂。 NDC编号为0074-0063-28。
Dasabuvir，ombitasvir，paritaprevir和ritonavir 200mg/8.33mg/50mg/ 33.33mg片剂是淡黄色的，薄膜包衣的，长方形的，在一侧用“3QD”凹陷。
储存温度应低于30°C（86°F）。
完整处方资料附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2e9dc175-80cb-b598-d035-4c3d5134c096
FDA Green Lights AbbVie (ABBV) Once-Daily Viekira XR for Hepatitis C
AbbVie Receives U.S. FDA Approval of Once-Daily VIEKIRA XR™ (dasabuvir, ombitasvir, paritaprevir and ritonavir) for the Treatment of Genotype 1 Chronic Hepatitis C
-- New extended-release formulation is the first all-oral, co-formulated treatment containing the three direct-acting antiviral components of VIEKIRA PAK® for adult patients with genotype 1 (GT1) chronic hepatitis C virus (HCV) infection
- The approval marks another milestone in AbbVie's ongoing commitment to therapeutic innovation for people living with GT1 HCV
U.S. Food and Drug Administration (FDA) has approved a New Drug Application (NDA) for VIEKIRA XR (dasabuvir, ombitasvir, paritaprevir and ritonavir) extended-release tablets. VIEKIRA XR is a once-daily, extended-release co-formulation of the active ingredients in VIEKIRA PAK® (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets) and is for the treatment of patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection, including those with compensated cirrhosis (Child-Pugh A). VIEKIRA XR is not for people with decompensated cirrhosis.
VIEKIRA XR is the first co-formulated three direct-acting antiviral (DAA) treatment for adult patients with GT1 HCV. VIEKIRA XR is given once-daily as three oral tablets and must be taken with a meal. It is used without ribavirin (RBV) in GT1b patients and in combination with twice daily RBV in GT1a patients. The approval is supported by Phase 3 clinical trials for VIEKIRA PAK which include data that demonstrated 100 percent sustained virologic response 12 weeks following treatment (SVR12) in GT1b patients with 12 weeks of therapy without ribavirin and 95 percent SVR12 in GT1a patients when used with ribavirin for 12 or 24 weeks of therapy.
"AbbVie's work continues to contribute to the transformation of hepatitis C care through our focus on evolving our current therapies as part of our ongoing commitment to patients," said Rob Scott, M.D., vice president, development and chief medical officer, AbbVie. "The approval of VIEKIRA XR provides a new treatment option for genotype 1 hepatitis C patients in the U.S. with clinical trial data using the components of VIEKIRA XR demonstrating 100 percent cure rates in genotype 1b patients."
There are six major HCV genotypes (GT1-6) and GT1 is the most preva lent form of HCV in the U.S., accounting for approximately 74 percent of all cases.1 Hepatitis C continues to be an important public health issue, with the Centers for Disease Control and Prevention (CDC) estimating that in the U.S. approximately 2.7 million people are chronically infected with HCV.2
The approval of VIEKIRA XR is supported by data from seven Phase 3 clinical trials in more than 2,300 patients who received VIEKIRA PAK with or without RBV for 12 or 24 weeks and two bioavailability studies comparing the formulations.
About Clinical Studies
The components of VIEKIRA XR (administered twice daily with a meal) have been studied in seven Phase 3 clinical trials where 1076 subjects (including 181 with compensated cirrhosis) received the recommended regimen of VIEKIRA +/ RBV for 12 weeks, or for 24 weeks in GT1a patients with compensated cirrhosis. Ninety-five to 100 percent achieved SVR12, which means the hepatitis C virus is not detectable in the blood three months after treatment ends. Cure rates varied by the subtype of hepatitis C and whether or not the person had cirrhosis. Individual results may vary.
USE
VIEKIRA XR (dasabuvir, ombitasvir, paritaprevir, and ritonavir) extended-release tablets/VIEKIRA PAK® (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets) (VIEKIRA) are prescription medicines used with or without ribavirin to treat adults with genotype 1 chronic (lasting a long time) hepatitis C (hep C) virus infection.
VIEKIRA can be used in people who have compensated cirrhosis.
VIEKIRA is not for people with advanced cirrhosis (decompensated). If people have cirrhosis, they should talk to a doctor before taking VIEKIRA.
IMPORTANT SAFETY INFORMATION
When taking VIEKIRA in combination with ribavirin, people should read the Medication Guide that comes with ribavirin, especially the important pregnancy information.
What is the most important information to know about VIEKIRA?
VIEKIRA may cause severe liver problems, especially in people with certain types of cirrhosis. These severe liver problems can lead to the need for a liver transplant, or can lead to death.
VIEKIRA can cause increases in liver function blood test results, especially if people use ethinyl estradiol-containing medicines (such as some birth control products).
Ethinyl estradiol-containing medicines (combination birth control pills or patches, such as Lo Loestrin® FE, Norinyl®, Ortho Tri-Cyclen Lo®, Ortho Evra®; hormonal vaginal rings such as NuvaRing®; and the hormone replacement therapy medicine, Fem HRT®) must be stopped before starting treatment with VIEKIRA. If these medicines are used as a method of birth control, another method must be used during treatment with VIEKIRA, and for about 2 weeks after treatment with VIEKIRA ends. A doctor can provide instruction on when to begin taking ethinyl estradiol-containing medicines.
A doctor should do blood tests to check liver function during the first 4 weeks of treatment and then as needed.
A doctor may tell people to stop taking VIEKIRA if signs or symptoms of liver problems develop. A doctor must be notified right away if any of the following symptoms develop or if they worsen during treatment with VIEKIRA: tiredness, weakness, loss of appetite, nausea, vomiting, yellowing of the skin or eyes, color changes in stools, confusion, or swelling of the stomach area.
VIEKIRA must not be taken if people:
have certain liver problems
take any of the following medicines: alfuzosin hydrochloride (Uroxatral®) carbamazepine (Carbatrol®, Epitol®, Equetro®, Tegretol®, TEGRETOL®-XR, TERIL®) cisapride (Propulsid®) colchicine (Colcrys®), in patients who have certain kidney or liver problems dronedarone (Multaq®) efavirenz (Atripla®, Sustiva®) ergot-containing medicines, including ergotamine tartrate (Cafergot®, Ergomar®, Ergostat®, Medihaler®, Migergot®, Wigraine®, Wigrettes®), dihydroergotamine mesylate (D.H.E. 45®, Migranal®), methylergonovine (Ergotrate®, Methergine®) ethinyl estradiol-containing medicines gemfibrozil (Lopid®) lovastatin (Advicor®, Altoprev®, Mevacor®) lurasidone (Latuda®) midazolam (when taken by mouth) phenytoin (Dilantin®, Phenytek®) phenobarbital (Luminal®) pimozide (Orap®) ranolazine (Ranexa®) rifampin (Rifadin®, Rifamate®, Rifater®, Rimactane®) sildenafil citrate (Revatio®), when taken for pulmonary artery hypertension (PAH) simvastatin (Simcor®, Vytorin®, Zocor®) St. John's wort (Hypericum perforatum) or a product that contains St. John's
wort triazolam (Halcion®)
have had a severe skin rash after taking ritonavir (Norvir®)
What should people tell a doctor before taking VIEKIRA?
If they have: liver problems other than hep C infection, HIV infection, or any other medical conditions.
If they have had a liver transplant.
If they take the medicines tacrolimus (Prograf®) or cyclosporine (Gengraf®, Neoral®, Sandimmune®), a doctor should check blood levels and, if needed, may change the dose of these medicines or how often they are taken, both during and after treatment with VIEKIRA.
If they are pregnant or plan to become pregnant or if they are breastfeeding or plan to breastfeed. It is not known if VIEKIRA will harm a person's unborn baby or pass into breast milk. A doctor should be consulted about the best way to feed a baby if taking VIEKIRA.
About all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some medicines interact with VIEKIRA.
A new medicine must not be started without telling a doctor. A doctor will provide instruction on whether it is safe to take VIEKIRA with other medicines.
When VIEKIRA is finished, a doctor should be consulted on what to do if one of the usual medicines taken was stopped or if the dose changed during VIEKIRA treatment.
What are the common side effects of VIEKIRA?
For VIEKIRA used with ribavirin, side effects include tiredness, nausea, itching, skin reactions such as redness or rash, sleep problems, and feeling weak.
For VIEKIRA used without ribavirin, side effects include nausea, itching, and sleep problems.
These are not all of the possible side effects of VIEKIRA. A doctor should be notified if there is any side effect that is bothersome or that does not go away.
This is the most important information to know about VIEKIRA. For more information, talk to a doctor.
People are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.