美国生物制药公司Medimmune(Nasdaq:MEDI)在2007年2月15日的新英格兰医学杂志(NEJM)上发表文章,总结了该公司的喷鼻剂型流感疫苗FluMist的婴幼儿临床研究结果,引发公司股价大幅上扬1.77美元/股,或5.7%至收盘价33.20美元/股。 FluMist在2003年就获批上市,虽然在使用方式上大大优于注射型疫苗,但并没有在商业上获得成功。主要原因是FluMist批准使用范围是5-49岁的健康人,实际上,小于5岁和长于49岁的人群才更加需要流感疫苗。另外,FluMist的储存需要冷冻以及保险公司不愿意承担更高的费用都是商业上失利的原因。FluMist这次扩大适用范围的临床研究在美国、欧洲、亚洲和中东的249个医疗中心进行,共有8475名12至59个月龄的儿童(无哮喘和气喘)参加。结果表明FluMist组明显优于对照组(传统的注射型疫苗),其患流感住院的例数比对照低55%。这次Medimmune也优化了FluMist的储存条件,新剂型为CAIV-T,可存放于4℃冰箱。预计FluMist的扩大适应范围将于2007-2008年获得批准,最早可能是2007年5月28日。目前,唯一用于4岁以下儿童的流感疫苗是Sanofi(NYSE:SNY)的Fluzone,可用于6个月龄的儿童。其他在美国销售流感疫苗的还有GlaxoSmithKline(NYSE:GSK)和Novarits(NYSE:NVS)。FluMist和其他疫苗的区别是前者是活的、减毒病毒,后者则是失活病毒。
美国亿万富翁Carl Icahn宣称已拥有2800万股MEDI的股票,也是该公司股票升值的原因。MEDI当日拒绝了某股东提出的出售本公司的建议,也拒绝和其他公司或投资者洽谈公司出售。
英文原文摘要:
Live Attenuated versus Inactivated Influenza Vaccine in Infants and Young Children
Robert B. Belshe, M.D., Kathryn M. Edwards, M.D., Timo Vesikari, M.D., Steven V. Black, M.D., Robert E. Walker, M.D., Micki Hultquist, M.S., George Kemble, Ph.D., Edward M. Connor, M.D., for the CAIV-T Comparative Efficacy Study Group
ABSTRACT
Background Universal vaccination of children 6 to 59 months of age with trivalent inactivated influenza vaccine has recently been recommended by U.S. advisory bodies. To evaluate alternative vaccine approaches, we compared the safety and efficacy of intranasally administered live attenuated influenza vaccine with those of inactivated vaccine in infants and young children.
Methods Children 6 to 59 months of age, without a recent episode of wheezing illness or severe asthma, were randomly assigned in a 1:1 ratio to receive either cold-adapted trivalent live attenuated influenza vaccine (a refrigeration-stable formulation of live attenuated intranasally administered influenza vaccine) or trivalent inactivated vaccine in a double-blind manner. Influenza-like illness was monitored with cultures throughout the 2004–2005 influenza season.
Results Safety data were available for 8352 children, and 7852 children completed the study according to the protocol. There were 54.9% fewer cases of cultured-confirmed influenza in the group that received live attenuated vaccine than in the group that received inactivated vaccine (153 vs. 338 cases, P<0.001). The superior efficacy of live attenuated vaccine, as compared with inactivated vaccine, was observed for both antigenically well-matched and drifted viruses. Among previously unvaccinated children, wheezing within 42 days after the administration of dose 1 was more common with live attenuated vaccine than with inactivated vaccine, primarily among children 6 to 11 months of age; in this age group, 12 more episodes of wheezing were noted within 42 days after receipt of dose 1 among recipients of live attenuated vaccine (3.8%) than among recipients of inactivated vaccine (2.1%, P=0.076). Rates of hospitalization for any cause during the 180 days after vaccination were higher among the recipients of live attenuated vaccine who were 6 to 11 months of age (6.1%) than among the recipients of inactivated vaccine in this age group (2.6%, P=0.002).
Conclusions Among young children, live attenuated vaccine had significantly better efficacy than inactivated vaccine. An evaluation of the risks and benefits indicates that live attenuated vaccine should be a highly effective, safe vaccine for children 12 to 59 months of age who do not have a history of asthma or wheezing. (ClinicalTrials.gov number, NCT00128167 [ClinicalTrials.gov] .)
Hospitalization rates for culture-confirmed influenza among young children are similar to those among the elderly, and outpatient visits for confirmed influenza are more frequent among infants and young children than in any other age group.1 For these reasons, U.S. advisory bodies have recently recommended the routine vaccination of all children 6 to 59 months of age with the licensed trivalent inactivated influenza vaccine.2 The implementation of this recommendation will be challenging because of the limited supplies of inactivated vaccine during many influenza seasons,3,4,5 the modest efficacy of inactivated vaccine in young children,6 and the frequent need to administer the inactivated vaccine by injection concurrent with multiple other parenteral vaccines.
Previous clinical trials of live attenuated trivalent influenza vaccine in young children have shown it to be highly effective.7,8,9 Live attenuated influenza vaccine showed high efficacy when epidemic influenza viruses were not well matched to the recommended vaccine antigens.7 Initial studies comparing the efficacy of cold-adapted trivalent live attenuated influenza vaccine with trivalent inactivated vaccine have shown the former to be more effective (35 to 53% reduction in the influenza attack rate with live attenuated vaccine, as compared with inactivated vaccine).10,11 Although the safety of live attenuated influenza vaccine was assessed in children in both prospective and database studies,12,13,14,15 additional prospective studies of both inactivated vaccine and live attenuated vaccine were needed. In one study,15 but not in others,10,11,16 wheezing events were more frequent among young children given formulations of live attenuated vaccine. The present trial was designed to assess the safety and relative efficacy of live attenuated intranasal influenza vaccine and inactivated vaccine in children 6 to 59 months of age.
Figure 1. Kaplan–Meier Curves for the Time to the First Culture-Confirmed Report of Influenza in the Two Vaccine Groups.
Culture-confirmed influenza was caused by any wild-type influenza strain (regardless of antigenic match or mismatch to vaccine) in children who received a study vaccine according to the study protocol (P<0.001 by the log-rank test). Of 3936 children given inactivated vaccine, 338 had influenza, and of 3916 children given live attenuated vaccine, 153 had influenza. Each square denotes one infected child in the inactivated-vaccine group, and each circle one infected child in the live-attenuated-vaccine group.
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