Progressing PfSPZ vaccines for malaria to licensure and commercialization

摘要 Sanaria的使命是许可和销售恶性疟原虫(PF)子孢子(SPZ)疫苗 防治疟疾，可防止疟疾在个人中感染和传播，并可在公共场合使用 以健康为导向的疟疾控制和消除计划。这项建议的目的是将时间缩短到 通过资助开发计划的各个方面来许可和销售Sanaria的PfSPZ疫苗 通常通过第二阶段或第二阶段B赠款或合同得到支持。尽管每年投资30亿美元 疟疾控制，2020年非洲死于疟疾的人数超过了新冠肺炎和627,000人- 可归因性死亡人数为2012年以来的最高水平。2021年推荐的RTS S/AS01型疟疾疫苗 世卫组织用于幼儿，在预防疟疾住院方面效果有限(21%)和严重 疟疾(30%)，没有报告对肺吸虫感染的保护。因此，现有的工具是不够的，而且 人们仍然迫切需要高效疫苗。迫切需要的是一种高效的疫苗， 预防疟疾感染，以支持消除疟疾。我们的第一代Sanaria®PfSPZ疫苗基于 辐射减弱的PfSPZ在5个月至61岁的儿童中安全且耐受性良好，在9个月的21个临床试验中 非洲有6个国家。它对异源控制的人类疟疾感染有很好的保护作用。 在非洲进行至少18年的现场试验，用于至少8米和显著的VE，以防止严重的自然肺炎传播 最近，它在两年内预防了非洲有生育潜力的妇女的临床疟疾 疟疾传播季节超过18米，没有加强。非洲儿童和儿童的额外临床试验 孕妇和印度尼西亚士兵将于2022年第2/3季度开始使用PfSPZ疫苗，以满足 第三阶段合规性。最令人兴奋的是，Sanaria已经开发出一种迟捕、复制能力强的(LARC) PfSPZ-LARC2疫苗，预计效力是第一种疫苗的5-10倍，价格更低 新一代疫苗。商业化推动了我们走向商业化的进程 就绪性试点计划(CRPP)。然而，来自顾问的建议，与欧洲的沟通 药品管理局(EMA)和美国FDA，疫苗现场试验的令人兴奋的结果，以及技术 PfSPZ-LARC2的发展都对我们的计划产生了重大影响。因为Sanaria的所有PfSPZ疫苗 利用相同的制造、质量和监管流程以及临床试验设计， 我们正在进行的CRP计划没有改变；相反，我们的创新和发展发现了新的 制造、质量、监管和临床任务没有在正在进行的CRPP中提供资金，这些任务是必需的 用于实现最有效和最具成本效益的PfSPZ疫苗的许可和商业化。本CRPP 将根据我们顾问的意见、建议，促进专业套餐的制作 来自EMA和FDA，以及我们的技术进步。成功将大大缩短产品上市前的时间 发放许可证和启动，从而促进销售，挽救受疟疾影响的许多人的生命。

ABSTRACT Sanaria’s mission is the licensure and marketing of Plasmodium falciparum (Pf) sporozoite (SPZ) vaccines against malaria that will prevent malaria infection and transmission in individuals and can be used in public health-driven malaria control and elimination programs. The aim of this proposal is to shorten the time to licensure and marketing of Sanaria’s PfSPZ vaccines by funding aspects of the development program not typically supported through Phase II or Phase IIB grants or contracts. Despite annual investments of >$3 B in malaria control, malaria killed more people in Africa in 2020 than did COVID-19 and the 627,000 malaria- attributable deaths were the highest since 2012. The RTS,S/AS01 malaria vaccine, recommended in 2021 by WHO for use in young children, has limited efficacy in preventing malaria hospitalizations (21%) and severe malaria (30%), and no reported protection against Pf infection. Thus, existing tools are inadequate, and a highly effective vaccine is still desperately needed. The critical need is for a highly efficacious vaccine that prevents malaria infection to support malaria elimination. Our 1st generation Sanaria® PfSPZ vaccine, based on radiation attenuated PfSPZ, is safe and well tolerated in 5-month- to 61-year-olds in 21 clinical trials in 9 countries, 6 in Africa. It induces excellent protection against heterologous controlled human malaria infection for at least 8 m and significant VE against intense natural Pf transmission in field trials in Africa for at least 18 m. Most recently it protected against clinical malaria in African women of child-bearing potential during two malaria transmission seasons over 18 m without boosting. Additional clinical trials in African children and pregnant women and Indonesian soldiers will start in Q2/3 2022 using PfSPZ Vaccine manufactured to meet Phase 3 compliance. Most excitingly, Sanaria has developed a late-arresting, replication competent (LARC) vaccine, PfSPZ-LARC2 that is expected to be 5-10 times more potent and less expensive than the 1st generation vaccine. Our progress toward commercialization has been facilitated by a Commercialization Readiness Pilot Program (CRPP). However, advice from consultants, communications with the European Medicines Agency (EMA) and US FDA, exciting results of field trials of the vaccine, and the technological development of PfSPZ-LARC2 have all significantly affected our program. As all of Sanaria’s PfSPZ vaccines utilize the same manufacturing, quality, and regulatory processes and clinical trial designs, the overall aims of our ongoing CRP program have not changed; rather our innovations and developments have identified new manufacturing, quality, regulatory and clinical tasks not funded in the ongoing CRPP, tasks that are required for achieving licensure and commercialization of the most potent and cost effective PfSPZ vaccine. This CRPP will facilitate production of the professional packages responsive to our consultants’ advice, recommendations from the EMA and FDA, and to our technical advances. Success will significantly shorten the time until product licensure and launch, and consequently to sales and saving many lives of those affected by malaria.