NEJM:Sofosbuvir用于慢性丙肝病毒感染初治安全有效

2013-04-30 NEJM dxy

在2期临床试验中,核苷酸聚合酶抑制剂sofosbuvir用于基因1,2或3型慢性丙肝病毒(HCV)感染的初治患者表现出良好的效果。新西兰奥克兰市立医院的Eric Lawitz博士等人日前发表于国际权威杂志NEJM上的研究显示,在sofosbuvir联用聚乙二醇干扰素-2a(peginterferon-2a)和利巴韦林治疗HCV感染者(多为1或4亚型)的单组试验中发现,治疗12周时有90%的患者出现

在2期临床试验中,核苷酸聚合酶抑制剂sofosbuvir用于基因1,2或3型慢性丙肝病毒(HCV)感染的初治患者表现出良好的效果。新西兰奥克兰市立医院的Eric Lawitz博士等人日前发表于国际权威杂志NEJM上的研究显示,在sofosbuvir联用聚乙二醇干扰素-2a(peginterferon-2a)和利巴韦林治疗HCV感染者(多为1或4亚型)的单组试验中发现,治疗12周时有90%的患者出现持续性病毒应答。在非劣效性试验中,2或3型感染者接受sofosbuvir联用利巴韦林治疗方案或聚乙二醇干扰素-2a(peginterferon-2a)联用利巴韦林方案后应答率相似,均为67%。Sofosbuvir引起的不良事件发生率较聚乙二醇干扰素-2a(peginterferon-2a)低。

据估计,世界范围内有一亿七千万患者感染HCV,最常见的是基因型1型HCV。这些感染了HCV的患者中,80%会发展成慢性感染。慢性丙肝中,20%的患者会发展成肝硬化,有25%的可能发展成肝癌。尽管现在还没有疫苗可以预防丙肝,但它是一种有治愈希望的疾病。

研究人员开展了将该药用于未经治疗的HCV感染者的3期临床试验。该单组、公开标签研究中,研究者对327例1、4、5、6型HCV感染者(其中98%为1或4亚型)应用sofosbuvir联用聚乙二醇干扰素-2a(peginterferon-2a)和利巴韦林12周治疗方案。在非劣效性试验中,感染基因2或3型HCV的499例患者经随机分组后,分别接受sofosbuvir联用利巴韦林治疗12周方案或聚乙二醇干扰素-2a(peginterferon-2a)和利巴韦林12周治疗方案。在此两项研究中,主要终点是治疗结束后12周的持续病毒学应答情况。

结果显示,在单组研究中,90%的患者出现持续病毒学应答(95% 置信区间,87%-93%)。在非劣效性试验中,研究发现sofosbuvir联用利巴韦林治疗组和聚乙二醇干扰素-2a(peginterferon-2a)和利巴韦林治疗组均有67%的患者出现持续病毒学应答。Sofosbuvir联用利巴韦林治疗方案中,基因3型HCV染者的应答率较2型感染者低(56% vs. 97%)。研究显示,sofosbuvir治疗引起的不良事件(包括,头疼,恶心,嗜中性白细胞减少症)较聚乙二醇干扰素-2a(peginterferon-2a)少。

文章作者写道,在sofosbuvir联用聚乙二醇干扰素-2a和利巴韦林治疗HCV感染者(多为1或4型)的单组试验中发现,治疗后12周时,有90%的患者出现持续性病毒应答。在非劣效性试验中,2或3型感染者接受sofosbuvir联用利巴韦林治疗方案或聚乙二醇干扰素-2a(peginterferon-2a)和利巴韦林治疗方案后应答率相似,均为67%。Sofosbuvir引起的不良事件发生率较聚乙二醇干扰素-2a低。

药物:Sofosbuvir/GS-7977

开发者:吉利德科学公司

适应证:丙型肝炎病毒

开发阶段:Ⅲ期

相关临床研究结果:针对25例患者的Ⅱ期研究显示,丙肝病毒基因1型感染者服用该核苷酸药物及吉利德的NS5A抑制剂GS-5885,其SVR4达到了100%。而且其副作用是可以接受的。

inThought获批指数和评价:该药的inThought获批指数为60%。Sofosbuvir是十分有前途的丙肝治疗药物。预计该药获批时间为2015年3月。

分析师评价:GfK HealthCare研究和咨询部高级副总裁马里捷·塔博认为,Sofosbuvir属于每日一次口服剂,比目前每周注射一次的相关治疗药物更便捷。如果该药物没有安全问题出现,2014年有望获得批准。不过该药也面临着其他新的口服丙型肝炎病毒治疗药物的竞争。
丙肝相关的拓展阅读:

Sofosbuvir for Previously Untreated Chronic Hepatitis C Infection
Background
In phase 2 trials, the nucleotide polymerase inhibitor sofosbuvir was effective in previously untreated patients with chronic hepatitis C virus (HCV) genotype 1, 2, or 3 infection.
Methods
We conducted two phase 3 studies in previously untreated patients with HCV infection. In a single-group, open-label study, we administered a 12-week regimen of sofosbuvir plus peginterferon alfa-2a and ribavirin in 327 patients with HCV genotype 1, 4, 5, or 6 (of whom 98% had genotype 1 or 4). In a noninferiority trial, 499 patients with HCV genotype 2 or 3 infection were randomly assigned to receive sofosbuvir plus ribavirin for 12 weeks or peginterferon alfa-2a plus ribavirin for 24 weeks. In the two studies, the primary end point was a sustained virologic response at 12 weeks after the end of therapy.
Results
In the single-group study, a sustained virologic response was reported in 90% of patients (95% confidence interval, 87 to 93). In the noninferiority trial, a sustained response was reported in 67% of patients in both the sofosbuvir-ribavirin group and the peginterferon-ribavirin group. Response rates in the sofosbuvir-ribavirin group were lower among patients with genotype 3 infection than among those with genotype 2 infection (56% vs. 97%). Adverse events (including fatigue, headache, nausea, and neutropenia) were less common with sofosbuvir than with peginterferon.
Conclusions
In a single-group study of sofosbuvir combined with peginterferon-ribavirin, patients with predominantly genotype 1 or 4 HCV infection had a rate of sustained virologic response of 90% at 12 weeks. In a noninferiority trial, patients with genotype 2 or 3 infection who received either sofosbuvir or peginterferon with ribavirin had nearly identical rates of response (67%). Adverse events were less frequent with sofosbuvir than with peginterferon. (Funded by Gilead Sciences; FISSION and NEUTRINO ClinicalTrials.gov numbers, NCT01497366 and NCT01641640 , respectively.).

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