PfSPZ Vaccine for Prevention of Plasmodium falciparum malaria

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 rt5 times as many disability adjusted life years lost worldwide in 2020 than COVID-19. Despite investments of rt$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 rt90% 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.