PfSPZ Vaccine for Prevention of Plasmodium falciparum malaria

摘要 该项目的目的是对萨那里亚恶性疟原虫(PF)进行关键的临床试验。 子孢子虫(SPZ)疫苗，Sanaria®PfSPZ疫苗，为旅行者提供许可证支持。这是一个重要的 为最需要许可证的未得到充分服务的人群提供许可证，特别是在非洲。迫在眉睫 新冠肺炎强调了疟疾疫苗的研发。2020年非洲有更多人死于疟疾 据估计，新冠肺炎和疟疾导致的残疾调整后寿命是前者的5倍 2020年全球损失的年数比新冠肺炎还多。尽管每年在疟疾控制方面投入30亿美元， 2019年是疟疾连续第5年没有显著减少；现有工具是 不足以取得进一步进展。此外，疟疾仍然是国际社会关注的一个主要问题。 旅行者，特别是每年访问撒哈拉以南非洲的4400万人。有一份紧急的未得到满足的医疗报告 需要一种预防个人疟疾的疫苗，并可以在大规模疫苗接种计划中部署，以 支持消除疟疾。Sanaria的领先疫苗产品PfSPZ疫苗，由辐射减毒， 无菌、纯化、低温保存的PfSPZ已在1726名婴儿、儿童和成人中安全和耐受性良好 在9个国家进行了20项临床试验，其中6项在非洲。它已经诱导了90%的疫苗对同源病毒的效力(VE 在美国、德国、马里和美国，控制的人类疟疾感染(CHMI)在免疫后3-11周 在2.5个月和8个月时，VE对异源CHMI的抵抗率分别为80%和54%；VE对天然烈性CHMI的抵抗率为80%和54% 在非洲进行了4次现场试验，传播了PF疟疾，持续时间至少为18个月。萨纳里亚已经开发出一种 通过首先接收PfSPZ疫苗来更快地开发、许可和营销PfSPZ疫苗的创新方法 基于一项关键的3期临床试验，PfSPZ疫苗在非洲旅行者中的营销授权 160名受试者，而不是通常的约3000名受试者。这项计划被提交给欧洲医药公司 2021年初，联合国环境规划署(EMA)和EMA原则上同意我们的做法。有明确的许可途径 欧盟，我们正在迅速推进向EMA提出的临床计划，并修改 EMA推荐。这项提案要求支持美国--将在美国进行的临床试验的一半 美国和德国(将在FDA和保罗-埃利希研究所(PEI)的监督下进行)。在中国的审判 160名受试者被设计用来测试是否有可能拒绝零假设，即没有 疫苗接种者和对照组在研究对象的比例上存在显著差异 免疫后2、6、10周出现异种CHMI后寄生虫血症。基座 根据这次试验的结果，以及我们已经产生和正在产生的非洲实地试验的结果，我们 预计能够成功申请任何疟疾的第一个许可证(营销授权) 疫苗在欧洲或美国。成功将大大缩短产品获得许可和推出之前的时间， 这将大大早于没有这个项目的销售，并拯救许多人的生命。

ABSTRACT The aim of this project is to conduct a pivotal clinical trial of Sanaria’s Plasmodium falciparum (Pf) whole sporozoite (SPZ) vaccine, Sanaria® PfSPZ Vaccine, to support licensure for travelers. This is an important step toward licensure for the underserved populations who need it most, especially in Africa. The urgency of developing a malaria vaccine has been highlighted by COVID-19. Malaria killed more people in Africa in 2020 than did COVID-19 and malaria was responsible for an estimated >5 times as many disability adjusted life years lost worldwide in 2020 than COVID-19. Despite investments of >$3 billion annually in malaria control, 2019 was the 5th consecutive year in which there was no meaningful decrease in malaria; existing tools are inadequate to make further progress. In addition, malaria continues to be a major concern for international travelers, especially the 44 million who visit sub-Saharan Africa annually. There is an urgent unmet medical need for a vaccine that prevents malaria in individuals, and can be deployed in mass vaccination programs to support malaria elimination. Sanaria’s lead vaccine product PfSPZ Vaccine, composed of radiation-attenuated, aseptic, purified, cryopreserved PfSPZ, has been safe and well tolerated in 1726 infants, children and adults in 20 clinical trials in 9 countries, 6 in Africa. It has induced >90% vaccine efficacy (VE) against homologous controlled human malaria infection (CHMI) at 3-11 weeks after immunization in the US, Germany, Mali and Tanzania; 80% and 54% VE against heterologous CHMI at 2.5 and 8 months; and VE against intense naturally transmitted Pf malaria in 4 field trials in Africa with durability of at least 18 months. Sanaria has developed an innovative approach to more rapidly developing, licensing, and marketing PfSPZ Vaccine by first receiving marketing authorization for PfSPZ Vaccine for use in travelers to Africa based on a pivotal Phase 3 clinical trial of 160 subjects instead of the usual ~3,000 subjects. This plan was presented to the European Medicines Agency (EMA) in early 2021 and the EMA agreed in principle to our approach. With a clear path to licensure in the EU, we are moving forward expeditiously with the clinical plan proposed to the EMA with modifications the EMA recommended. This proposal requests support for the US-half of a clinical trial that will be conducted in the US and Germany (to be conducted under both FDA and Paul-Ehrlich Institute (PEI) oversight). The trial in 160 subjects is designed to test whether it is possible to reject the null hypothesis that there will be no significant difference between vaccinees and controls with regard to the proportion of research subjects developing parasitemia following heterologous CHMI conducted 2, 6 and 10 weeks after immunization. Based on results from this trial, along with results we have generated and are generating from field trials in Africa, we anticipate being able to successfully apply for the first licensure (marketing authorization) of any malaria vaccine in Europe or the US. Success will significantly shorten the time until product licensure and launch, which will lead to sales significantly earlier than without this project, and save many lives.