By Anthony Aisi
The results from the pivotal, large-scale Phase III clinical trial, released on Friday (9 November) suggest promising results for a new malaria vaccine, despite a drop in efficacy from last year.
The results, released at the International African Vaccinology Conference in Cape Town, South Africa, found that infants (aged 6-12 weeks at first vaccination) vaccinated with the RTS,S vaccine had one-third fewer episodes of both clinical and severe malaria compared to those immunised with a control vaccine.
The trial also found RTS,S demonstrated an acceptable safety and tolerability profile and that infants in both groups reacted in similar ways to the vaccinations given.
Dr. Salim Abdulla, from Tanzania’s Ifakara Health Institute, who is a principal investigator for the trial, said: “We’ve made significant progress in recent years in our battle against malaria, but the disease still kills 655,000 people a year—mainly children under five in sub-Saharan Africa. An effective malaria vaccine would be a welcome addition to our tool kit, and we’ve been working toward this goal with this RTS,S trial.”
Importantly, insecticide-treated bed nets were used by 86% of the trial participants. This demonstrates that RTS,S can provide protection beyond existing malaria control interventions.
Dr Abdulla added: “This study indicates that RTS,S can help to protect young babies against malaria. Importantly, we observed that it provided this protection in addition to the widespread use of bed nets by the trial participants.”
A total of 11 African research centres in seven African countries are conducting the trial together with GlaxoSmithKline (GSK) and the PATH Malaria Vaccine Initiative (MVI), with grant funding from the Bill & Melinda Gates Foundation to MVI.
Efficacy of the malaria RTS,S vaccine
In this phase of the trial, when administered along with standard childhood vaccines, the efficacy of RTS,S in infants aged 6 to 12 weeks (at first vaccination) against clinical and severe malaria was 31% and 37% respectively over 12 months and after a third vaccine dose. However, the efficacy observed with RTS,S last year in children aged 5-17 months was 56% (clinical) and 47% (severe) respectively.Follow-up will continue and is expected to provide more data for analyses to better understand the different findings between the age categories.
Dr. Abdulla said: “The efficacy is lower than what we saw last year with the older 5-17 month age category, which surprised some of us scientists at the African trial sites. It makes us even more eager to gather and analyse more data from the trial to determine what factors might influence efficacy against malaria and to better understand the potential of RTS,S in our battle against this devastating disease.
“We were also glad to see that the study indicated that RTS,S could be administered to young infants along with standard childhood vaccines and that side effects were similar to what we would see with those vaccines.”
There was no increase in overall reporting of serious adverse events between the infants vaccinated with the RTS,S malaria vaccine candidate and infants in the control group, which received a comparator vaccine.
Sir Andrew Witty, CEO of GlaxoSmithKline, said: “While the efficacy seen is lower than last year, we believe these results confirm that RTS,S can help provide African babies and young children with meaningful protection against malaria. They take us another important step forward on the journey towards having a new intervention available against this disease, which is a huge burden on the health and economic growth of Africa.
“We remain convinced that RTS,S has a role to play in tackling malaria and we will continue to work with our partners and other stakeholders to better understand the data and to define how the vaccine could best be used to provide public health benefit to children in malaria endemic areas in Africa.”
David Kaslow, Director of the PATH Malaria Vaccine Initiative, said: “Determining the role of RTS,S in Africa will depend on analyses of additional data. We are now an important step closer to that day. Success in developing malaria vaccines depends on many factors: at the top of the list are partnerships and robust evidence, coupled with an understanding that different combinations of tools to fight malaria will be appropriate in different settings in malaria-endemic countries. My congratulations go out to the team at GSK and to the African research centres for their exemplary conduct of this trial.”
“This is an important scientific milestone and needs more study,” said Bill Gates, co-founder of the Bill & Melinda Gates Foundation.
“The efficacy came back lower than we had hoped, but developing a vaccine against a parasite is a very hard thing to do. The trial is continuing and we look forward to getting more data to help determine whether and how to deploy this vaccine.”
More data on the longer-term efficacy of the vaccine during 30 months of follow-up after the third dose, and the impact of a booster dose are expected to be publicly available at the end of 2014.
The World Health Organisation has indicated that a policy recommendation for the RTS,S malaria vaccine candidate is possible as early as 2015 if the required regulatory approvals are obtained and public health information, including safety and efficacy data from the Phase III programme, deemed satisfactory. If the policy recommendation goes ahead it will pave the way for decisions by African nations regarding large-scale implementation of the vaccine through their national immunisation programmes.
An effective vaccine for use alongside other measures such as bed nets and anti-malarial medicines would represent a decisive advance in malaria control.
The vaccine is being developed in partnership by GSK and MVI, together with prominent African research centres. The collaborators are represented on the Clinical Trials Partnership Committee, which oversees the conduct of the trial. An extended team of organisations work on RTS,S, including scientists from across Africa, Europe, and North America. Major funding for clinical development of RTS,S comes from a grant by the Bill & Melinda Gates Foundation to MVI.
Should RTS,S be approved and recommended for use GSK and MVI say they are committed to making the vaccine available to those who need it most. In January 2010, GSK announced that the eventual price of RTS,S (also known as MosquirixTM) will cover the cost of manufacturing the vaccine together with a small return of around 5% that will be reinvested in research and development for second-generation malaria vaccines or vaccines against other neglected tropical diseases.