Final results of Phase III trial of RTS,S Malaria vaccine published in The Lancet-Glaxo Smith Kline

Final results from a large-scale Phase III trial of RTS,S malaria vaccine candidate, from Glaxo Smith Kline, including the impact of a booster dose, have been published in The Lancet and show that the vaccine helped protect children and infants from clinical malaria for at least three years after first vaccination. The results demonstrated that vaccination with RTS,S, followed by a booster dose administered 18 months later reduced the number of cases of clinical malaria in children (aged 5-17 months) by 36% to the end of the study and in infants (aged 6-12 weeks) by 26% to the end of the study. Efficacy decreased over time in both age groups. Without the booster dose, the 3-dose primary schedule reduced clinical malaria cases by 28% in children and 18% in infants to the study end.

The efficacy of RTS,S was evaluated in the context of existing malaria control measures, such as insecticide treated bed nets. For children 5-17 months who received a booster dose, an average of 1,774 cases of malaria were prevented for every 1,000 children vaccinated, over an average of 48 months of follow-up. For infants aged 6-12 weeks who received a booster dose, 983 cases of malaria, were prevented for every 1,000 infants vaccinated over an average of 38 months of follow-up. More cases were averted in areas of higher malaria transmission. In the absence of a booster dose, 1,363 cases of clinical malaria were prevented, on average, for every 1,000 children aged 5-17 months at first vaccination and 558 cases for every 1,000 infants aged 6-12 weeks at first vaccination to the end of the study.

Statistically significant efficacy against severe malaria to the end of the study period was observed only in children who received the booster dose. There was indication of increased risk for severe malaria in children who did not receive the booster dose, compared to those in the control group. RTS,S continued to display an acceptable safety and tolerability profile during the entire study period.

Comment: Data shows that this new vaccine could prevent a substantial number - millions - of cases of clinical malaria, especially in areas of high transmission. But there are still questions. For instance, the meningitis signal previously reported remains in the older age category, including two cases reported after the booster dose of RTS,S. This could be a chance finding, as comparisons were made across groups for many different diseases, and because some of these cases happened years after vaccination without any obvious relationship to vaccination. The occurrence of meningitis will be followed closely during Phase IV studies, if RTS,S is licensed. RTS,S also produced more adverse reactions than the control vaccines. Convulsions following vaccination, although uncommon, occurred more frequently in children who received RTS,S/AS01 than in controls.