Progressing PfSPZ vaccines for malaria to licensure and commercialization

推进 PfSPZ 疟疾疫苗的许可和商业化

• 批准号: 10602357
• 负责人: STEPHEN Lev HOFFMAN
• 金额: $ 99.99万
• 依托单位: SANARIA, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-14 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10602357
• 关键词: Acceleration; Address; Affect; Africa; African; Attenuated; Attenuated Vaccines; Authorization documentation; COVID-19; Cessation of life; Characteristics; Child; Clinical; Clinical Trials; Clinical Trials Design; Code; Communicable Diseases; Communication; Computer Systems; Contracts; Country; Cryopreservation; Databases; Development; Development Plans; Disease; Dose; Ensure; Europe; European; Falciparum Malaria; Feedback; Funding; Generations; Glass; Goals; Grant; Hospitalization; Human; Immunize; Individual; Infant; Infection; Infection prevention; Infrastructure; Investments; Licensure; Liver; Malaria; Malaria Vaccines; Marketing; Medicine; Mission; Morbidity - disease rate; Parasites; Persons; Pharmaceutical Preparations; Phase; Plasmodium falciparum; Plasmodium falciparum vaccine; Pregnancy; Pregnant Women; Procedures; Process; Production; Program Development; Public Health; Qualifying; Quality Control; Radiation; Readiness; Recommendation; Regulation; Reporting; Safety; Sales; Seasons; Soldier; Sporozoite vaccine; Technology; Time; Travel; Vaccination; Vaccines; Validation; Vial device; Woman; attributable mortality; authority; child bearing; clinical development; commercialization; commercialization readiness; cost effective; design; implementation trial; innovation; malaria infection; malaria transmission; manufacture; meetings; mortality; novel vaccines; prevent; programs; protective efficacy; public health intervention; public health relevance; quality assurance; response; stem; stillbirth; success; technology development; tool; transmission process; vaccine efficacy; vaccine trial; Acceleration; Address; Affect; Africa; African; Attenuated; Attenuated Vaccines; Authorization documentation; COVID-19; Cessation of life; Characteristics; Child; Clinical; Clinical Trials; Clinical Trials Design; Code; Communicable Diseases; Communication; Computer Systems; Contracts; Country; Cryopreservation; Databases; Development; Development Plans; Disease; Dose; Ensure; Europe; European; Falciparum Malaria; Feedback; Funding; Generations; Glass; Goals; Grant; Hospitalization; Human; Immunize; Individual; Infant; Infection; Infection prevention; Infrastructure; Investments; Licensure; Liver; Malaria; Malaria Vaccines; Marketing; Medicine; Mission; Morbidity - disease rate; Parasites; Persons; Pharmaceutical Preparations; Phase; Plasmodium falciparum; Plasmodium falciparum vaccine; Pregnancy; Pregnant Women; Procedures; Process; Production; Program Development; Public Health; Qualifying; Quality Control; Radiation; Readiness; Recommendation; Regulation; Reporting; Safety; Sales; Seasons; Soldier; Sporozoite vaccine; Technology; Time; Travel; Vaccination; Vaccines; Validation; Vial device; Woman; attributable mortality; authority; child bearing; clinical development; commercialization; commercialization readiness; cost effective; design; implementation trial; innovation; malaria infection; malaria transmission; manufacture; meetings; mortality; novel vaccines; prevent; programs; protective efficacy; public health intervention; public health relevance; quality assurance; response; stem; stillbirth; success; technology development; tool; transmission process; vaccine efficacy; vaccine trial

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.

抽象的 Sanaria的使命是恶性疟原虫（PF）Sporozoite（SPZ）疫苗的许可和营销 反对疟疾会防止疟疾感染和个体传播，可以在公共场合使用 健康驱动的疟疾控制和消除计划。该提议的目的是缩短时间 通过资助开发计划的方面，SANARIA的PFSPZ疫苗的许可和营销 通常通过II期或IIB期赠款或合同支持。尽管年度投资> 3美元 疟疾控制，疟疾在2020年丧生的人数比1920年的疟疾人数多于1920年，而627,000疟疾杀死了疟疾。 可归因于2012年以来最高的死亡。RTS，S/AS01疟疾疫苗，建议于2021年由 谁在幼儿使用，预防疟疾住院（21％）和严重的效率有限 疟疾（30％），没有报告防止PF感染的保护。那是现有工具不足，一个 仍然需要高效的疫苗。关键需求是一种高效的疫苗 防止疟疾感染以支持消除疟疾。我们的第一代SANARIA®PFSPZ疫苗，基于 在5个月至61岁的21个临床试验中，radiotion减弱了PFSPZ，在9个月至61岁的5个月中具有良好的耐受性 国家，6个非洲。它诱导了针对异源控制的人类疟疾感染的极好的保护 至少8 m，在非洲的野外试验中，至少有18个M的自然PF传播至少18个 m。最近，它保护了两次具有育儿潜力的非洲妇女的临床疟疾 疟疾传输季节超过18 m而不会增加。非洲儿童和 孕妇和印尼士兵将使用制造的PFSPZ疫苗在第二季度/3 2022年开始 第三阶段合规性。最令人兴奋的是，萨纳里亚（Sanaria）开发了较晚的复制能力（LARC） 疫苗，PFSPZ-LARC2的潜力将比第一个高出5-10倍，便宜 发电疫苗。我们通过商业化准备了商业化的进展 就绪试点计划（CRPP）。但是，顾问的建议，与欧洲的沟通 药品局（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的开发都严重影响了我们的计划。作为Sanaria的所有PFSPZ疫苗 利用相同的制造，质量和监管过程以及临床试验设计，总体目的 我们正在进行的CRP计划没有改变；而是我们的创新和发展已经确定了新的 制造，质量，监管和临床任务未在正在进行的CRPP中资助，所需的任务 用于实现最潜在和成本效益的PFSPZ疫苗的许可和商业化。这个crpp 将促进对我们顾问的建议的响应的专业套餐的生产 来自EMA和FDA，以及我们的技术进步。成功将大大缩短时间直到产品 许可和启动，因此销售并挽救了受疟疾影响的人的许多生命。