Phase 2 trial shows 77% efficacy for malaria vaccine candidate R21
The results of a Phase IIb randomized, controlled, double-blind trial conducted at the Clinical Research Unit of Nanoro (CRUN) / Institut de Recherche en Sciences de la Santé (IRSS), Burkina Faso indicate 77% efficacy over 12 months of follow-up for a vaccine that targets malaria caused by Plasmodium falciparum. The study included 450 participants, aged 5–17 months, from the catchment area of Nanoro, covering 24 villages and an approximate population of 65,000 people. This is the first malaria vaccine candidate to meet the World Health Organization’s Malaria Vaccine Technology Roadmap goal of at least 75% efficacy.
R21 was produced by expressing recombinant Hepatitis B surface antigen (HBsAg) virus-like particles in Hansenula polymorpha, comprising the central repeat and the C-terminus of the Plasmodium falciparum circumsporozoite protein (CSP), fused to the N-terminal end of HBsAg. It is manufactured by the Serum Institute of India Private Ltd (SIIPL). R21 was mixed prior to administration with Matrix-M, a saponin-based vaccine adjuvant produced by Novavax AB, Uppsala, Sweden.
The low-dose circumsporozite protein-based vaccine (R21) developed by researchers with Oxford University, in collaboration with Novavax and Serum Institute of India, was tested with two different doses of Matrix-M (MM) adjuvant in 450 children ages 5 to 17 months in Nanoro, Burkina Faso, a highly seasonal malaria transmission setting. Three vaccinations were administered at 4-week intervals prior to and during the start of the malaria season, with a fourth dose given 1 year later. Investigators in the randomized, controlled, double-blind trial evaluated safety, immunogenicity, and efficacy with the high- and low-dose adjuvants and compared the results with a control group that received a rabies vaccine.
At 6 months, 33 of 146 (29.5%) children who received R21/MM with low-dose adjuvant and 38/146 (26%) who received R21/MM with high-dose adjuvant developed malaria, compared with 105/147 (71.4%) who received the rabies vaccine. Vaccine efficacy (VE) was 74% and 77% in the low- and high-dose adjuvant groups, respectively, and at 1 year, VE remained at 77% in the high-dose adjuvant group. Both adjuvant dosage levels were well tolerated, with fever the most common adverse event reported. No severe adverse reactions were reported.
Following these results, the Phase IIb trial, which was funded by the EDCTP2 programme supported by the European Union (grant number RIA2016V-1649-MMVC), was extended with a booster vaccination administered prior to the next malaria season one year later. The researchers, in collaboration with Serum Institute of India Private Ltd., and Novavax Inc., have now started recruitment for a Phase III licensure trial to assess large-scale safety and efficacy in 4,800 children, aged 5–36 months, across four African countries.
Dr. Halidou Tinto, Professor in Parasitology, Regional Director of IRSS in Nanoro, and the trial Principal Investigator said: ‘These are very exciting results showing unprecedented efficacy levels from a vaccine that has been well tolerated in our trial programme. We look forward to the upcoming phase III trial to demonstrate large-scale safety and efficacy data for a vaccine that is greatly needed in this region.’
Dr. Cyrus Poonawalla and Mr. Adar Poonawalla, Chairman and CEO of the Serum Institute of India said: ‘We are highly excited to see these results on a safe and highly effective malaria vaccine which will be available to the whole world through an excellent collaborative effort between Serum Institute, the University of Oxford and Novavax Inc.. Serum Institute is committed to global disease burden reduction and disease elimination strategies by providing high volume, affordable vaccines. We are highly confident that we will be able to deliver more than 200 million doses annually in line with the above strategy as soon as regulatory approvals are available.’
There were an estimated 229 million cases of malaria worldwide in 2019, with 409,000 deaths. Children under 5 years old accounted for 67% of those deaths.