LONDON (TIP): The world’s first malaria vaccine has passed its final test but the results haven’t been emphatic.

The results demonstrated that vaccination with RTS,S, followed by a booster dose administered 18 months after the primary schedule, reduced the number of cases of clinical malaria in children (aged 5-17 months at first vaccination) by 36% over an average follow-up of four years.

This however was a fall in efficacy from the 50% protection against malaria which was seen in the first year after the vaccine was administered.

In infants (aged 6-12 weeks at first vaccination) it reduced malaria cases by only 26% to the end of the study (an average follow-up of 38 months).

Efficacy decreased over time in both age groups.

Without the booster dose, the three-dose vaccine only reduced clinical malaria cases by 28% in children and 18% in infants to the study end.

The vaccine against malaria, which does not exist at present, will therefore, be available in the market by next year. Pharma company GSK has submitted a regulatory application to the European Medicines Agency (EMA) for RTS,S.

In an exclusive interview to TOI from Ghana, Dr Kwaku Poku Asante, the chair of the Clinical Trial Partnership Committee, which managed the RTSS Phase 3 trial in Africa said “The good news is that this a first generation malaria vaccine candidate and) actually the first human parasite vaccine that has been developed to this level. This trial was conducted at 11 African research centres in seven countries. The RTSS malaria vaccine has now been shown to prevent 1,700 cases of clinical malaria per 1000 children vaccinated on average and more than 6,000 cases averted in an area of high malaria transmission”.

He added “It is true that the efficacy fell off over the four year period. But what we learned from the trial is that the booster dose enhanced efficacy over the longer term for both age groups. It will be up to the regulatory authorities to determine what efficacy is sufficient for recommendation, but it is likely that they will also look at the public health impact and the large number of cases averted through the use of the vaccine. The data from this trial has been submitted to the European Medicine Agency for review and an opinion on the data is expected sometime late this year”.

“It is not a setback to see an efficacy of 26% in infants. Indeed beyond the low efficacy results, 983 cases of clinical malaria, on average, were prevented for every 1,000 infants vaccinated across trial sites over an average of 38 months of follow-up. More cases were averted in areas of higher malaria transmission. There are two paths in the future for the RTS,S candidate vaccine: the regulatory pathway and the research pathway”. “On the regulatory pathway, the EMA is currently reviewing the regulatory application for RTS,S. A positive opinion from the EMA together with a potential policy recommendation from the World Health Organisation (anticipated by the end of 2015), would be the basis for licensure applications. If positive, these regulatory decisions would help pave the way for the introduction of RTS,S through African national immunisation programmes”.

“The next step in the research pathway is what we call Pharmacovigilance studies or phase 4 studies. These are very large-scale studies meant to identify very rare reactions or occurrences of clinical events to a vaccine,” he added

Brian Greenwood, author and professor of clinical tropical medicine at London School of Hygiene and Tropical Medicine in the UK explains, “Despite the falling efficacy over time, there is still a clear benefit from RTS,S/AS01. An average 1363 cases of clinical malaria were prevented over 4 years of follow-up for every 1000 children vaccinated, and 1774 cases in those who also received a booster shot. Over 3 years of follow-up, an average 558 cases were averted for every 1000 infants vaccinated and 983 cases in those also given a booster dose”.