Progressing PfSPZ vaccines for malaria to licensure and commercialization

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.