辉瑞（Pfizer）3月20日宣布，FDA已授予双价疫苗rLP2086突破性疗法认定，目前辉瑞正调查rLP2086用于10-25岁群体，预防B群脑膜炎奈瑟菌（Neisseria meningitidis serogroup B，MenB）导致的侵袭性脑膜炎球菌病。据估计，在全球范围内，MenB每年导致的侵袭性脑膜炎球菌病病例数达2万-8万例，并可能导致死亡或长期残疾，包括脑损伤和听力丧失。

突破性疗法认定的授予，部分基于调查rLP2086安全性和免疫原性的2项临床研究数据。其中一项研究表明，rLP2086在健康青少年（11-18岁）群体中诱导了可有效对抗MenB的杀菌抗体，同时具有可接受的安全性，该项研究的数据支持了推进rLP2086至进一步III期评估。另一项II期研究数据也表明，rLP2086 2针和3针免疫方案在健康青少年（11-18岁）群体中具有可接受的安全性。

目前，辉瑞正在开展rLP2086的一项全球临床开发项目，并计划于2014年中期向FDA提交rLP2086的生物制品许可申请（BLA）。

B群奈瑟脑膜炎球菌是导致青少年和年轻成人患细菌性脑膜炎和败血症的主要原因之一。现有的许可疫苗都不能提供针对MenB的广谱免疫保护。

rLP2086是一种实验性双价疫苗，基于2种LP2086蛋白（又名H因子结合蛋白，factor H-binding proteins，fHBPs），该蛋白存在于MenB的表面。fHBPs的基因，存在于1800株MenB分离株中。因此，rLP8026有望针对MenB产生广谱免疫保护。

Pfizer Inc. (PFE) announced today that the United States Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to Pfizer’s vaccine candidate, bivalent rLP2086, currently under investigation for the prevention of invasive meningococcal disease due to Neisseria meningitidis serogroup B in persons 10 C 25 years of age. Disease caused by Neisseria meningitidis serogroup B has been estimated at between 20,000 and 80,000 cases per year globally, and can result in death or significant long-term disabilities, including brain damage and hearing loss.1,2

Enacted as part of the 2012 FDA Safety and Innovation Act (FDASIA), Breakthrough Therapy designation is intended to expedite the development and review of potential new medicines for serious and life-threatening diseases.3 A Breakthrough Therapy designation conveys FDA's existing fast track development program features, as well as more intensive FDA guidance on an efficient drug development program.4

“Pfizer is developing this meningococcal B vaccine candidate to help protect adolescents and young adults against a difficult to diagnose and often deadly disease,” said Dr. Emilio Emini, senior vice president of Vaccine Research and Development for Pfizer Inc. “We are encouraged by the FDA’s recognition of the need to prevent meningococcal B disease, and the Breakthrough Therapy designation highlights the urgent need for prevention of meningococcal B disease.”

Pfizer is conducting a global clinical development program for rLP2086, which includes both Phase 2 and Phase 3 trials eva1uating more than 20,000 participants, ab0ut 14,000 of whom will receive the investigational vaccine.5,6,7,8,9,10,11,12 Following interactions that we have had with the FDA, Pfizer intends to submit a Biologics License Application (BLA) to the FDA for bivalent rLP2086 by mid-2014.

Invasive meningococcal disease is a rapidly progressing disease that can lead to serious disabilities and can be life-threatening for those infected.2 Of the five meningococcal serogroups (A, B, C, W-135 and Y) that historically have been responsible for the majority of meningococcal disease,13 serogroup B is the only one for which no broadly-protective vaccine is currently approved in the U.S. 13,14

ab0ut rLP2086

Pfizer’s investigational meningococcal B vaccine targets LP2086, or factor H-binding protein, which is found on the surface of the meningococcal B bacterium. The gene for factor H-binding protein is present in the more than 1,800 meningococcal B isolates Pfizer researchers have studied.15

The Breakthrough Therapy designation was based, in part, on data from two clinical trials studying the safety and immunogenicity of rLP2086. Clinical data from a Phase 2 study published in the Lancet Infectious Diseases showed the investigational rLP2086 vaccine induced bactericidal antibodies in healthy adolescents (aged 11-18 years) that were broadly active against meningococcal B bacteria.16 Safety data from the study also showed the vaccine had an acceptable safety profile in this healthy adolescent study population and supported the further eva1uation of the vaccine in Phase 3 studies.16

In addition, data from another Phase 2, randomized, placebo-controlled, single-blind study of two- and three-dose schedules of rLP2086 in healthy adolescents (aged 11-18 years), showed that the investigational vaccine had an acceptable safety profile.17 Injection site pain was the most common adverse event.17 This study, presented at the Meningitis Research Foundation 2013 meeting, also showed that one month after the last vaccine dose in the two- and three-dose groups, 86-99% (after 3 doses) of subjects and 69-100% (after 2 doses) of subjects had hSBA titers (functional antibodies) greater than or equal to 1:8 to each meningococcal B test strain.17 The study results supported further eva1uation of a three dose regimen in the Phase 3 program.

In November 2012, the Phase 3 program began with the initiation of a large scale safety study. Additional immunogenicity and safety studies are also ongoing.

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