丙型肝炎是一种引起肝脏炎症的病毒性疾病，可能导致肝功能减退或肝衰竭。据2016年的统计数据，全球有1.3至1.5亿丙肝患者。中国慢性丙肝患者约为1000万人，其中250万人急需治疗。针对那些之前用抗病毒药物未治愈的丙肝患者，美国食品和药物管理局（FDA）近日批准了一种新的复方药片。
Vosevi用于治疗慢性丙型肝炎病毒（HCV）1-6型且无肝硬化（肝病）或轻度肝硬化的患者。Vosevi是一种固定剂量的复方药片，含有两种先前批准的药物——sofosbuvir和velpatasvir，以及一种新药——voxilaprevir。Vosevi是第一个被批准用于之前已经使用sofosbuvir或其他药物的患者的治疗，这些药物通过抑制一种名为NS5A的蛋白质，直接作用于HCV。
FDA药品评估与研究中心抗菌产品主任Edward Cox博士称，直接作用的抗病毒药物可以防止病毒增殖并常用于治疗HCV。Vosevi为一些过去其他药物未成功治愈的患者提供治疗选择。
一些慢性HCV的患者可能出现黄疸（眼睛或皮肤黄）和发生并发症，如出血、腹部积水、感染、肝癌和死亡。有至少6种不同的HCV基因型或菌株，它们在基因方面是不同的病毒组。了解病毒的毒株可以为提出治疗建议提供帮助。大约有75%的美国人有1型HCV1；20~25%的人有2型或3型；少数患者感染了4型、5型或6型。
通过两个3期临床试验来评估安全性和有效性，纳入大约750名无肝硬化和无轻度肝硬化的成年人。
第一项试验对比了接受12周Vosevi治疗与安慰剂的1型HCV成年患者，并且他们之前接受的NS5A抑制剂药物的治疗失败了。2型、3型、4型、5型或6型的患者都接受了Vosevi。
第二项试验对12周Vosevi治疗与之前批准的药物sofosbuvir和velpatasvir对1型、2型或3型成年患者进行了对比，这些患者使用sofosbuvir治疗失败而非NS5A抑制剂。
两项试验的结果显示，在完成治疗后的12周内，接受Vosevi治疗的患者中，有96~97%的患者在血液中没有发现病毒，这表明患者的感染已经治愈。
对Vosevi的治疗建议因病毒基因型和既往治疗史有差异。服用Vosevi的患者最常见的不良反应是头痛、疲劳、腹泻和恶心。Vosevi对正在服用利福平的患者禁忌。
已经报告在共同感染HCV/HBV的成年患者中乙型肝炎病毒（HBV）再激活，他们正在接受或已经完成了HCV直接作用的抗病毒药物治疗，并且没有接受HBV抗病毒治疗。对HBV再激活患者使用直接作用的抗病毒药物治疗，可能会导致一些病人出现严重的肝脏问题或死亡。卫生保健专业人员应该在使用Vosevi前对所有患者进行筛查，以确定当前或此前是否有HBV感染。
FDA批准了优先审查的应用和突破性治疗的设计，批准Vosevi上市。
INDICATION
VOSEVI is indicated for the treatment of adults with chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis who have:
•genotype 1, 2, 3, 4, 5 or 6 and were previously treated with an NS5A inhibitor.
•genotype 1a or 3 and were previously treated with sofosbuvir without an NS5A inhibitor; additional benefit of VOSEVI over sofosbuvir/velpatasvir was not shown in adults with genotype 1b, 2, 4, 5 or 6 infection in this population.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS
Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with VOSEVI. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.
Contraindications
•VOSEVI is contraindicated with rifampin.
Warnings and Precautions
•Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with VOSEVI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. A fatal cardiac arrest was reported in a patient taking amiodarone who was coadministered a sofosbuvir containing regimen. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical eva luation if they develop signs or symptoms of bradycardia.
•Risk of Reduced Therapeutic Effect Due to Concomitant Use of VOSEVI with P-gp Inducers and/or Moderate to Potent Inducers of CYP2B6, CYP2C8 or CYP3A4: St. John's wort and carbamazepine are not recommended for use with VOSEVI as they may significantly decrease sofosbuvir, velpatasvir, and/or voxilaprevir plasma concentrations.
Adverse Reactions
•The most common adverse reactions (≥10%, all grades) with VOSEVI were headache, fatigue, diarrhea, and nausea.
Drug Interactions
•Coadministration of VOSEVI is not recommended with phenytoin, phenobarbital, oxcarbazepine, rifabutin, rifapentine, atazanavir, lopinavir, tipranavir/ritonavir, efavirenz, rosuvastatin, pitavastatin, and cyclosporine due to changes (decreased or increased) in concentrations of sofosbuvir, velpatasvir, voxilaprevir, and/or the other agent.
Consult the full Prescribing Information for VOSEVI for more information on potentially significant drug interactions, including clinical comments. |
