Progressing PfSPZ vaccines for malaria to licensure and commercialization

摘要 Sanaria的使命是为恶性疟原虫（Pf）子孢子（SPZ）疫苗颁发许可证并进行销售 可预防疟疾感染和传播，并可在公共场所使用 健康驱动的疟疾控制和消除方案。这项建议的目的是缩短时间， 通过资助开发项目的各个方面， 通常通过II期或IIB期赠款或合同提供支持。尽管每年投资超过30 B美元， 疟疾控制，2020年疟疾在非洲造成的死亡人数超过COVID-19和627，000疟疾- 可归因死亡人数为2012年以来最高。RTS，S/AS 01疟疾疫苗，建议在2021年 世卫组织用于幼儿，在预防疟疾住院治疗（21%）和严重 疟疾（30%），没有报告对Pf感染的保护。因此，现有的工具是不够的， 仍然迫切需要高效的疫苗。迫切需要一种高效的疫苗， 预防疟疾感染，以支持消灭疟疾。我们的第一代Sanaria® PfSPZ疫苗，基于 在9个月至61岁的21项临床试验中， 国家，6个在非洲。它诱导对异源受控人疟疾感染的极好保护 在非洲进行的田间试验中， M.最近，在两个月内，它保护了有生育能力的非洲妇女免受临床疟疾的侵害。 疟疾传播季节超过18米，没有增加。在非洲儿童中进行的其他临床试验， 孕妇和印尼士兵将于2022年第二季度开始使用PfSPZ疫苗， 第三阶段合规。最令人兴奋的是，Sanaria已经开发出一种后期捕获的复制能力（LARC）。 PfSPZ-LARC 2疫苗，预计比第一种疫苗的效力高5-10倍，价格更低 一代疫苗。我们的商业化进程得到了商业化的促进。 准备试点计划（CRPP）。然而，顾问的建议，与欧洲 药品管理局（EMA）和美国FDA，疫苗的现场试验的令人兴奋的结果，以及技术 PfSPZ-LARC 2的发展都对我们的计划产生了重大影响。作为Sanaria的所有PfSPZ疫苗 使用相同的制造、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，我们的创新和发展已经确定了新的 正在进行的CRPP中未资助的制造、质量、监管和临床任务， 以实现最有效和最具成本效益的PfSPZ疫苗的许可和商业化。该CRPP 将有助于根据顾问的意见和建议， 以及我们的技术进步。成功将大大缩短产品上市的时间 许可证和发射，从而销售和拯救许多受疟疾影响的人的生命。

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.