每日1次复方片剂Stribild获准用于初治的HIV感染

圣路易斯(MD Consult) –2012年8月27日，Gilead Sciences公司与美国食品药品管理局(FDA)联合宣布，Stribild(埃替拉韦150 mg/cobicistat 150 mg/恩曲他滨200 mg/富马酸替诺福韦酯300 mg)每日1次的单一片剂方案已获准用于从未接受过治疗的成年人类免疫缺陷病毒-1(HIV-1)感染患者。Stribild包含以前批准的2种HIV治疗药物和2种新药——埃替拉韦和cobicistat。埃替拉韦是一种HIV整合酶链转移抑制剂，cobicistat是一种药代动力学增强剂，可抑制代谢某些HIV药物的酶，以延长埃替拉韦的疗效。恩曲他滨和延胡索酸泰诺福韦酯的复合制剂已于2004年通过核准，商品名为Truvada，可阻断HIV复制所需的另一种酶。

Stribild通过核准是基于2项3期关键研究的48周数据的支持，在这些研究中，单一片剂方案相对于Atripla(依非韦伦600 mg/恩曲他滨200 mg/富马酸替诺福韦酯300 mg)和一种包含利托那韦强化的阿扎那韦加Truvada(恩曲他滨/富马酸替诺福韦酯)治疗方案达到了非劣效性标准。这些研究旨在评估治疗48周后血液中检测不出HIV水平的患者百分率。结果显示，Stribild、Atripla和Truvada+阿扎那韦+利托那韦治疗者中，血液中检测不出HIV水平的患者分别占88%~ 90%、84%和87%。

在所有关于Stribild的研究中，多数不良事件为轻至中度。临床试验中观察到的常见不良反应包括恶心和腹泻。严重不良反应包括新发肾功能受损或肾功能受损加重、骨密度降低、脂肪再分配和免疫重建综合征。Stribild产品说明书中包含关于乳酸酸中毒/严重肝肿大伴脂肪变性以及治疗后乙型肝炎急性加重的黑框警告。

爱思唯尔版权所有  未经授权请勿转载

ST LOUIS (MD Consult) - On August 27, 2012, Gilead Sciences and the US Food and Drug Administration (FDA) announced the approval of Stribild (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg), a once-daily single tablet regimen for the treatment of human immunodeficiency virus-1 (HIV-1) infection in treatment-naïve adults. Stribild contains 2 previously approved HIV drugs plus 2 new drugs, elvitegravir and cobicistat. Elvitegravir is an HIV integrase strand transfer inhibitor, and cobicistat is a pharmacokinetic enhancer that inhibits an enzyme that metabolizes certain HIV drugs and is used to prolong the effect of elvitegravir. The combination of emtricitabine and tenofovir disoproxil fumarate, approved in 2004 and marketed as Truvada, blocks the action of another enzyme that is needed for HIV replication.

The approval of Stribild is supported by 48-week data from 2 pivotal phase 3 studies in which the single tablet regimen met its primary objective of noninferiority compared with Atripla (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg), and to a regimen containing ritonavir-boosted atazanavir plus Truvada (emtricitabine/tenofovir disoproxil fumarate). The studies were designed to measure the percentage of patients who achieved undetectable HIV blood levels after 48 weeks. Results showed that between 88% and 90% of patients treated with Stribild demonstrated undetectable blood levels of HIV, compared with 84% treated with Atripla and 87% treated with Truvada plus atazanavir and ritonavir.

In all studies of Stribild, most adverse events were mild to moderate in intensity. Common adverse effects observed in clinical trials include nausea and diarrhea. Serious adverse effects include new or worsening renal impairment, decreased bone mineral density, fat redistribution, and immune reconstitution syndrome. The Stribild label contains Boxed Warnings of lactic acidosis/severe hepatomegaly with steatosis, and post-treatment acute exacerbation of hepatitis B.