百时美施贵宝（BMS）在第21届逆转录病毒和机会性感染大会（CROI 2014）上公布了实验性HIV药物BMS-663068的IIb期临床数据，证实该药与增效剂ritonavir(利托那韦)增效的一种蛋白酶抑制剂Reyataz（atazanavir，阿扎那韦）具有类似的反应率（HIV-1 RNA <50 c/mL，表明病毒复制无法检测到），BMS-663068治疗组实现HIV-1 RNA<50 c/mL患者比例为69-80%，而对照组（ritonavir+Reyataz）比例为75%。这些数据令人鼓舞，并支持了BMS-663068的进一步开发。

该项研究彰显了实验性药物BMS-663068的独特作用机制，该药是一种新颖的吸附抑制剂，能够阻止病毒最初吸附宿主CD4+T细胞并进入宿主免疫细胞。

全球范围内，有多达3400万HIV感染者。由于过去20年中HIV治疗管理的显著科学进步，现在患者能带病生存更长的时间，但同时一些患者已对现有方案产生抗性或不耐受。新的治疗选择，尤其是新的药物类别，无论现在或将来，对这类群体都很必要。

通过靶向病毒生命周期的早期阶段，BMS-663068有望以一种不同于现有抗逆转录病毒药物的独特作用方式，破坏HIV病毒。该项研究的数据表明，BMS-663068具有与当前标准药物之一Reyataz同样疗效的潜力，可能为经治（即既往治疗过）但失败同时需要新治疗方案的患者群体，提供另一种抑制病毒的方法。

该项主动控制IIb研究中，经治HIV-1成人感染者（n=254）随机平均分配至4个BMS-663068治疗组：400mg BID（每天2次），800mg BID，600mg QD（每日一次），1200mg QD；对照组Reyataz+ritonavir（300/100mg BID）。同时，每个治疗组及对照组还接受拉替拉韦（raltegravir，RAL，400mg BID）和替诺福韦（tenofovir，TDF，300mg BID）治疗。

主要终点为：治疗24周时，HIV-1 RNA＜50c/ml的患者比例，以及24周中由于严重不良事件（SAE）和不良事件（AE）导致的停药频率。

研究结果表明，整个24周中，BMS-663068与Reyataz+ritionavir治疗组表现出相似的疗效。具体来讲，BMS-663068 4个治疗组实现HIV-1 RNA＜50c/ml的患者比例为69%-80%，对照组为75%。研究中，BMS-663068耐受性良好，无严重不良事件或不良事件导致停药。

—BMS-663068 has a unique mechanism of action in treating HIV. It is the first investigational antiretroviral to prevent initial viral attachment to the host CD4+ T cell and entry into the host immune cell by binding directly to the HIV virus

—24 week Phase IIb data showed similar response rates (HIV-1 RNA <50 c/mL) in treatment-experienced patients treated with BMS-663068 compared to a boosted protease inhibitor

—Study data presented at the 2014 Conference on Retroviruses and Opportunistic Infections (CROI) demonstrated that BMS-663068 was generally well-tolerated in these study patients, with no adverse events leading to discontinuation

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today presented 24-week Phase IIb data that demonstrated similar response rates (HIV-1 RNA <50 c/mL) for its investigational compound, BMS-663068, when compared to a boosted protease inhibitor, Reyataz® (atazanavir sulfate) with ritonavir. Among HIV-1 infected treatment-experienced patients receiving BMS-663068, 69-80% had HIV-1 RNA levels of <50 c/mL (a measure indicating virus replication is undetectable), compared to 75% of patients taking Reyataz with ritonavir. Presented at the 21st Conference on Retroviruses and Opportunistic Infections (CROI) today, this study highlights the unique mechanism of action of the investigational prodrug BMS-663068, which when converted into BMS-626529, a novel attachment inhibitor, prevents initial viral attachment to the host CD4+ T cell and entry into the host immune cell.

Globally, there are 34 million people who are infected with HIV. Due to significant scientific advances in management of HIV treatment over the last 20 years, patients are now living with HIV for a longer period of time and some patients have developed resistance to existing regimens or are unable to tolerate current available treatments. Additional treatment options, especially in new drug classes, are needed both today and into the future for these patients.

“By targeting the virus at an earlier step of the viral lifecycle, BMS-663068 disrupts the virus in a way unlike existing antiretroviral agents,” said Jacob P. Lalezari, M.D., director of Quest Clinical Research and assistant clinical professor of medicine at UCSF/Mount Zion Hospital. “The data suggest that BMS-663068 is potentially as effective as one of the current standards of care and may provide another method of suppressing the virus in treatment-experienced patients who have failed a prior HIV regimen and need new treatment options.”

Study Design and Results

In this active-controlled Phase IIb study, treatment-experienced HIV-1 infected adults (n=254) were randomized equally to one of four BMS-663068 treatment arms: (400 mg BID (twice daily); 800 mg BID; 600 mg QD (once daily); 1200 mg QD) and, a control group of Reyataz® (atazanavir sulfate) and ritonavir (300/100 mg QD). Each treatment arm and the control group also included raltegravir (RAL) 400 mg BID and tenofovir disoproxil fumarate (TDF) 300 mg QD. The primary endpoints were the proportion of subjects with HIV-1 RNA <50 c/mL at week 24 and the frequency of serious adverse events (SAEs) and adverse events (AEs) leading to discontinuation through week 24.

Through week 24, BMS-663068 showed similar efficacy compared to Reyataz and ritonavir for treatment-experienced patients infected with HIV-1. Specifically, 69-80% of patients in the four treatment arms had HIV-1 RNA levels <50 c/mL, indicating virus replication was undetectable, compared to 75% of patients in the control group.

BMS-663068 was generally well-tolerated during the study, with no serious adverse events attributed to BMS-663068 nor any adverse events leading to discontinuation. The incidence of Grade 2-4 related AEs across BMS-663068 arms ranged from 3.9% to 12%, vs. 27.5% in the comparator arm (atazanavir sulfate and ritonavir) and no causal association was observed between adverse events and BMS-663068 dose.

“These study results are encouraging and support further development of BMS-663068 as we continue to look for ways to treat people living with HIV, especially those who have exhausted available therapies and are difficult to treat,” said Douglas Manion, M.D., senior vice president, Development, Virology, Bristol-Myers Squibb. “Bristol-Myers Squibb is committed to the fight against HIV and continues to study treatments with novel mechanisms of action in hopes of addressing the unmet needs of both patients recently diagnosed with HIV, treatment-naïve and treatment-experienced HIV-infected inpiduals throughout the world.”

About Bristol-Myers Squibb’s HIV Research Portfolio

For over 20 years, Bristol-Myers Squibb has focused on discovering, developing and delivering innovative medicines to help meet the needs of patients living with HIV/AIDS and continues to pursue advances in treatment, for both children and adults with HIV. Studies are ongoing for new treatments including an NRTI (BMS-986001), an attachment inhibitor prodrug (BMS-663068) and a maturation inhibitor (BMS-955176).

Bristol-Myers Squibb also continues to enhance its current product offerings for patients living with HIV/AIDS and is developing a fixed-dose combination of Reyataz® (atazanavir sulfate) and Gilead’s investigational drug cobicistat, which is currently in Phase III development. New bioequivalence (BE) data about this combination will also be featured in a poster presentation on March 6 at 2:30 p.m. during the 2014 Conference on Retroviruses and Opportunistic Infections.

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