Letter: Phase III efficacy trial of the RTS,S malaria vaccine candidate
On behalf of the PATH Malaria Vaccine Initiative, GlaxoSmithKline, and 11 African research centers in seven countries, we are writing to inform you that further results from the Phase III efficacy trial of the RTS,S malaria vaccine candidate are to be presented on Tuesday, 8 October, at the 6th Multilateral Initiative on Malaria (MIM) Pan-African Malaria Conference in Durban, South Africa. An article with additional findings and data is in preparation for submission to a peer-reviewed journal.
The results presented are the third set from the ongoing Phase III trial. Over 18 months of follow-up, RTS,S was shown to almost halve the number of malaria cases in young children (aged 5-17 months at first vaccination) and to reduce by around a quarter the malaria cases in infants (aged 6-12 weeks at first vaccination). These results were demonstrated in the context of existing malaria control measures, such as insecticide treated bednets, which were used by 78% of children and 86% of infants in the trial. The presentation abstract concluded by saying that the vaccine “shows potential for a role in malaria control in Africa.”
Over 18 months of follow-up, children aged 5-17 months at first vaccination with RTS,S experienced 46% (95% CI: 42 to 50) fewer cases of clinical malaria, compared to children immunised with a control vaccine; an average of 941 cases of clinical malaria were prevented for every 1,000 children vaccinated. Severe malaria cases were reduced by 36% (95% CI: 15 to 51), malaria hospitalisations by 42% (95% CI: 29 to 52), and all-cause hospitalizations by 19% (95% CI: 9 to 28).
Infants aged 6-12 weeks at first vaccination with RTS,S had 27% (95% CI: 20 to 32) fewer cases of clinical malaria. Over 18 months of follow-up, 444 cases of clinical malaria were prevented for every 1,000 infants vaccinated. The reduction of severe malaria cases and malaria hospitalisations was not statistically significant.
Vaccine efficacy was also assessed separately at each of the trial sites, which represented a wide range of malaria transmission settings; efficacy was found to be statistically significant at all sites in young children and at four sites in infants. At clinical trial sites where there were more cases of malaria, we found greater impact in both age groups.
RTS,S continued to display an acceptable safety and tolerability profile during the 18 month follow-up. Apart from the meningitis signal previously reported, no other safety signal was identified. The occurrence of meningitis will be followed closely during the remainder of the trial.
Based on these results, GSK now intends to submit, in 2014, a regulatory application to the European Medicines Agency (EMA). The World Health Organization (WHO) has indicated that a policy recommendation for the RTS,S malaria vaccine candidate is possible as early as 2015.
Follow-up in this Phase III trial is ongoing. Further data from 32 months follow-up and the impact of a fourth ‘booster’ dose given 18 months after the initial three doses are expected to become available in 2014.
The RTS,S malaria vaccine candidate is still under development and subject to the evaluation of the benefits and risks by regulatory authorities before being made available.
The abstract for the presentation at MIM is available at:
A press release on the findings is available at:
On behalf of the partners, we are,
David C. Kaslow, MD Sophie Biernaux
Vice President for Product Development Vice President and Malaria Vaccine Leader