2014年12月19日讯 /生物谷BIOON/ --葛兰素史克（GSK）带状疱疹疫苗HZ/su在关键III期研究（ZOE-50）大获成功，该疫苗有望使葛兰素史克不断扩张的疫苗单元每年新增10亿美元收入，同时将对默沙东已上市带状疱疹疫苗Zostavax形成严峻挑战。目前，Zostavax是上市的唯一一款带状疱疹疫苗。HZ/su的预期上市，也意味着默沙东在带状疱疹领域的垄断地位将不保。
根据葛兰素史克公布的数据，在关键III期临床中，与安慰剂相比，HZ/su使50岁及以上老年群体感染带状疱疹的风险降低97.2%。而默沙东Zostavax在50-59岁老年群体中的疗效数据仅为69.8%，在60岁以上老年群体中疗效更低。不过，不同的临床试验设计意味着将2者进行直接比较可能有点棘手。
Zostavax与HA/su的工作原理不同。Zostavax是一种活的减毒病毒疫苗，而HZ/su结合了带状疱疹病毒gE蛋白和佐剂系统AS01B，该佐剂系统旨在增强免疫应答反应。
葛兰素史克尚未透露HZ/su的上市时间表。该公司发言人表示，将在2015年搜集更多的临床数据。目前，葛兰素史克也正在开展额外的研究，在70岁及以上老年群体及免疫功能低下患者群体中评估HZ/su预防带状疱疹的能力。该公司还表示，将在未来几个月公布该项III期研究的整体安全性数据。
默沙东的Zostavax于2006年获FDA批准上市，是目前市面上唯一的带状疱疹疫苗，在2013年的销售额为7.58亿美元，并且仍将保持强劲增长，因为迄今为止只有少数老年人接种了疫苗。根据汤姆森路透，业界预测Zostavax在2019年的销售额将达到11亿美元。然而，鉴于卓越的疗效数据，瑞士银行预测，葛兰素史克的疫苗HZ/su的年销售额将突破10亿美元。
关于HZ/su的III期项目：
HZ/su III期临床项目涉及超过3.7万人，评估了HZ/su的疗效、安全性和免疫原性。除了老年群体，目前葛兰素史克正在免疫功能低下患者群体中调查HA/su，包括实体瘤和血液肿瘤患者群体、造血干细胞和肾移植受者及HIV感染者。
ZOE-50是一项随机、双盲、安慰剂对照、多中心跨国III期研究，涉及1.616万例50岁及以上老年受试者，带状疱疹疫苗HZ/su按2针免疫程序（0和2个月）接种。主要终点是HZ/su在横跨所有年龄组降低带状疱疹感染风险的整体疫苗有效性（VE），该研究中年龄组划分为50-59，60-69，70-79，80以上。
关于带状疱疹：
带状疱疹（shingles）是由水痘-带状疱疹病毒（VZV）引起的急性感染性皮肤病，典型表现为皮疹。由于病毒具有亲神经性，感染后可长期潜伏于脊髓神经后根神经节的神经元内，当抵抗力低下或劳累、感染、感冒时，病毒可再次生长繁殖，并沿神经纤维移至皮肤，使受侵犯的神经和皮肤产生强烈的炎症。皮疹一般有单侧性和按神经节段分布的特点，有集簇性的疱疹组成，并伴有疼痛；年龄愈大，神经痛愈重。该病好发于成人，发病率随年龄增大而呈显著上升，并发症包括结疤、视力并发症、继发性感染、神经麻痹和带状疱疹后遗神经痛(PHN)。
许多国家的数据表明，有超过90%的成年人伴有带状疱疹风险，50岁以上人群感染带状疱疹风险显著升高。
英文原文：Pivotal phase III study of GSK shingles candidate vaccine meets its primary endpoint
GSK today announced that a pivotal phase III study to assess the efficacy of HZ/su, an investigational vaccine for the prevention of shingles, has met its primary endpoint.
Analysis of the primary endpoint showed that HZ/su reduced the risk of shingles by 97.2 per cent in adults aged 50 years and older compared to placebo. These are the first results from the ZOster Efficacy study in adults aged 50 years and over (ZOE-50). The study, which started in August 2010, is ongoing in 18 countries and involves more than 16,000 individuals.
Alain Brecx, MD, Vaccine Development Leader at GSK said: “It’s great news that the ZOE-50 trial has met its primary endpoint and I would like to thank all those involved in the clinical development programme. If approved, this candidate vaccine may offer an important option for the prevention of shingles, a painful disease that negatively impacts peoples’ health and quality of life. We look forward to sharing these compelling results and additional data from the ZOE-50 study and the broader HZ/suclinical development programme with the scientific and regulatory communities.”
HZ/su is a new candidate vaccine that combines gE, a protein found on the virus that causes shingles, with an adjuvant system, AS01B,1 which is intended to enhance the immunological response.
The full set of safety data from the ZOE-50 trial is currently being analysed and will be disclosed in the coming months. The Independent Data Monitoring Committee (IDMC) for the ZOE-50 study, in its ongoing review of the safety information up to 31 May 2014, raised no concerns regarding the continuation of the trial. At this time, the safety profile of HZ/su in older adults is based on data from more than 440 subjects who received HZ/su in phase I and II clinical trials. The most common adverse events seen with HZ/su from these studies included local reactions (pain, redness, swelling at the injection site) and systemic symptoms (muscle pain, fatigue and headache).
Data from the ZOE-50 trial are expected to be presented at a forthcoming scientific conference and submitted for publication in a peer-reviewed journal.
Additional trials to evaluate the ability of HZ/su to prevent shingles are underway in people aged 70 and older and in immunocompromised people. These studies will evaluate the efficacy, safety, and immunological response of HZ/su in specific populations and whether it can prevent some of the complications of shingles, such as chronic neuropathic pain, also known as post-herpetic neuralgia (PHN).2
Notes to editors
About the ZOE-50 trial
The ZOE-50 study is a randomised, observer-blind, placebo-controlled, multicentre, multinational (North America, Europe, Latin America, Asia-Pacific) phase III trial involving 16,160 adults aged 50 years and older. Doses were given intramuscularly on a 2-dose schedule at 0 and 2 months. The primary endpoint of this study is the overall vaccine efficacy (VE) of the candidate vaccine HZ/su across all age cohorts compared to placebo in reducing the risk of developing shingles. The study includes subjects in the age ranges 50-59, 60-69, 70-79, and ³80 years.
About the phase III HZ/su study programme
Involving more than 37,000 subjects globally, the phase III programme for candidate vaccine HZ/su will evaluate its efficacy, safety and immunogenicity. In addition to older adults, HZ/su is being evaluated in immunocompromised patient populations, including solid and haematological cancer patients, haematopoietic stem cell and renal transplant recipients and HIV-infected people.
About shingles
Shingles typically presents as a painful, itchy rash that develops on one side of the body, as a result of reactivation of latent chickenpox virus (varicella zoster virus, VZV). Anyone who has been infected with VZV is at risk of developing shingles, with age and altered immune system being recognised as the main risk factors.3 Complications from shingles can include scarring, vision complications, secondary infection, nerve palsies and PHN, the most common complication.2,3
Data from many countries indicate that more than 90 per cent of adults are at risk for HZ,3,4 and a person’s risk for shingles increases sharply after 50 years of age. Risk of complications, including PHN and hospitalisation, also increase with age. The individual lifetime risk of developing HZ is approximately one in three people; however, for individuals aged 85 and over, this risk increases to one in two people.5