2014年8月27日讯 /生物谷BIOON/ --葛兰素史克（GSK）和辉瑞（Pfizer）合资公司ViiV Healthcare 近日宣布，三合一HIV药物Triumeq（dolutegravir/abacavir/lamivudine，dolutegravir/阿巴卡韦/拉米夫定，50mg/600mg/300mg）获FDA批准，用于HIV-1感染的治疗。Triumeq是ViiV首个基于dolutegravir的固定剂量组合HIV复方片，结合了整合酶链转移抑制剂dolutegravir和2种核苷类逆转录酶抑制剂（NRTI）阿巴卡韦和拉米夫定，为众多HIV感染者提供了一种新的单片治疗方案。
Triumeq的获批，是基于2个关键性III期研究的数据，其中一项III期研究（SINGLE）调查了dolutegravir和abacavir/lamivudine作为单独的片剂；另一项研究调查了固定剂量dolutegravir/abacavir/lamivudine作为单一片剂相对于dolutegravir片和abacavir/lamivudine片组合疗法的生物等效性。
7月中旬，ViiV Healthcare宣布，与强生（JNJ）签署了一项合作协议，开发和商业化含dolutegravir（商品名Tivicay）和rilpivirine（商品名Edurant）的复方片剂。此次合作，也代表着ViiV的首个外部合作。（详见《ViiV与杨森合作开发HIV药物Tivicay/Edurant复方片》）
Edurant（rilpivirine）为高活性的抗逆转录病毒治疗（HAART）药物之一，属于非核苷类逆转录酶抑制剂（NNRTI），通过阻断HIV复制来发挥作用，该药已获批与其他抗逆转录病毒药物联合用于初治HIV-1成人感染者的治疗。如果获批，这种dolutegravir/rilpivirine固定剂量组合疗法将有望为HIV感染者提供一种选择，一旦稳定抑制病毒载量后，可从当前标准的3种药物组合疗法转向dolutegravir/rilpivirine固定剂量组合疗法。
关于Triumeq：
Triumeq（dolutegravir/abacavir/lamivudine）为每日一次的实验性三合一HIV复方单片，该药是一种基于dolutegravir的HIV治疗方案，由固定剂量的dolutegravir、abacavir（阿巴卡韦）、lamivudine（拉米夫定）组成。
关于Tivicay（dolutegravir）：
Tivicay（dolutegravir）是一种HIV整合酶抑制剂，该药为每日一次的口服药物，已获FDA、欧盟、加拿大批准，与其他抗逆转录病毒制剂联合用于既往已治疗过、或初治HIV-1成人和12岁及以上青少年感染者的治疗。
2016年Tivicay成主流
此前，独立分析公司Datamonitor Healthcare发布报告指出，Tivicay若获欧盟批准，必将对全球HIV市场产生巨大的影响，到2016年，Tivicay必将成为HIV治疗的主流整合酶抑制剂。（详见《2022年全球HIV市场将达168亿美元》）
Tivicay疗效优于Prezista或Isentress
在临床试验中，Tivicay疗效优于强生（JNJ）的蛋白酶抑制剂Prezista（darunavir，地瑞那韦），同时与当前的标准护理药物整合酶抑制剂Isentress（raltegravir，拉替拉韦）疗效相当。Isentress由默沙东（Merck & Co）开发。
Datamonitor Healthcare分析师Joseph Hedden称，Tivicay与其他一些竞争药物不同，该药不需要与药物促进剂联合用药，同时也具有一个非常有吸引力的耐药属性。在接下来几年里，以整合酶抑制剂销售额计算，这些属性将推动Tivicay至排名第一的位置。
关于ViiV Healthcare：
ViiV医疗保健公司是葛兰素史克（GSK）和辉瑞（Pfizer）于2009年联合成立的HIV/AIDS药物研发公司，目前，GSK持有ViiV 76.5%的股份，辉瑞持有10%的股份，日本盐野义（Shionogi）持有10%的股份。（生物谷Bioon.com）
英文原文：ViiV Healthcare receives FDA approval for Triumeq® (abacavir, dolutegravir and lamivudine), a new single-pill regimen for the treatment of HIV-1 infection
22 August 2014
Issued: London, UK
ViiV Healthcare announced today that the US Food and Drug Administration (FDA) has approved Triumeq® (abacavir 600mg, dolutegravir 50mg and lamivudine 300mg) tablets for the treatment of HIV-1 infection.1 Triumeq is ViiV Healthcare’s first dolutegravir-based fixed-dose combination, offering many people living with HIV the option of a single-pill regimen that combines the integrase strand transfer inhibitor (INSTI) dolutegravir, with the nucleoside reverse transcriptase inhibitors (NRTIs) abacavir and lamivudine.
Triumeq alone is not recommended for use in patients with current or past history of resistance to any components of Triumeq. Triumeq alone is not recommended in patients with resistance-associated integrase substitutions or clinically suspected INSTI resistance because the dose of dolutegravir in Triumeq is insufficient in these populations. Before initiating treatment with abacavir-containing products, screening for the presence of a genetic marker, the HLA-B*5701 allele, should be performed in any HIV-infected patient, irrespective of racial origin. Products containing abacavir should not be used in patients known to carry the HLA-B*5701 allele.1
Dr Dominique Limet, Chief Executive Officer, ViiV Healthcare, said: “Today’s approval of Triumeq offers many people living with HIV in the US the first single-pill regimen containing dolutegravir. ViiV Healthcare is committed to delivering advances in care and new treatment options to physicians and people living with HIV. We are proud to announce this important milestone, marking the second new treatment to be approved in the US from our pipeline of medicines.”
This FDA approval is based primarily upon data from two clinical trials:
the Phase III study (SINGLE) of treatment-naïve adults, conducted with dolutegravir and abacavir/lamivudine as separate pills2,3
a bioequivalence study of the fixed-dose combination of abacavir, dolutegravir and lamivudine when taken as a single pill compared to the administration of dolutegravir and abacavir/lamivudine as separate pills.4
In the SINGLE study, a non-inferiority trial with a pre-specified superiority analysis, more patients were undetectable (HIV-1 RNA <50 copies/mL) in the dolutegravir and abacavir/lamivudine arm (the separate components of Triumeq) than in the Atripla®† (efavirenz, emtricitabine and tenofovir) arm, the most commonly used single-pill regimen. The difference was statistically significant and met the pre-specified test for superiority. The difference was driven by a higher rate of discontinuation due to adverse events in the Atripla arm.2, 3
At 96 weeks, 80% of participants on the dolutegravir-based regimen were virologically suppressed compared to 72% of participants on Atripla. Grade 2-4 treatment emergent adverse reactions occurring in 2% or more participants taking the dolutegavir-based regimen were insomnia (3%), headache (2%) and fatigue (2%).3
About HIV
HIV stands for the Human Immunodeficiency Virus. Unlike some other viruses, the human body cannot get rid of HIV, so once someone has HIV they have it for life.5-7
HIV infects specific cells of the immune system, called CD4 cells or T-cells. Over time, HIV can destroy so many of these cells that the body cannot fight off infections and disease. When this happens, HIV infection leads to Acquired Immunodeficiency Syndrome (AIDS) which is the final stage of HIV infection. There is no cure for HIV, but with early diagnosis and effective treatment most people with HIV will not go on to develop AIDS.5-7
An estimated 1.1 million people in the US are living with HIV.However, only 33 percent are taking the medication they need.8
About Triumeq
Triumeq is a fixed-dose combination containing the INSTI dolutegravir and the NRTIs abacavir and lamivudine.
Two essential steps in the HIV life cycle are replication – when the virus turns its RNA copy into DNA – and integration – the moment when viral DNA becomes part of the host cell’s DNA. These processes require two enzymes called reverse transcriptase and integrase. NRTIs and integrase inhibitors interfere with the action of the two enzymes to prevent the virus from replicating and further infecting cells.
Dolutegravir was approved in the US in August 2013 and in Europe in January 2014 under the brand name Tivicay®. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) granted a positive opinion on the Marketing Authorisation Application (MAA) for Triumeq on 26 June 2014. Regulatory applications are also being evaluated in other markets worldwide, including Australia, Brazil and Canada.
Tivicay and Triumeq are registered trademarks of the ViiV Healthcare group of companies.
