RTS,S malaria candidate vaccine reduces malaria by approximately one-third
in African infants
Results from ongoing Phase III clinical trial announced
International African Vaccinology Conference, Cape Town, South
Africa-Results from a pivotal, large-scale Phase III trial, published
online today in the New England Journal of Medicine, show that the RTS,S
malaria vaccine candidate can help protect African infants against
malaria. When compared to immunization with a control vaccine, infants
(aged 6-12 weeks at first vaccination) vaccinated with RTS,S had one-third
fewer episodes of both clinical and severe malaria and had similar
reactions to the injection. In this trial, RTS,S demonstrated an
acceptable safety and tolerability profile.
Eleven African research centres in seven African countries1 are conducting
this trial, together with GlaxoSmithKline (GSK) and the PATH Malaria
Vaccine Initiative (MVI), with grant funding from the Bill & Melinda Gates
Foundation to MVI.
Dr. Salim Abdulla, a principal investigator for the trial from the Ifakara
Health Institute, Tanzania, 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. 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."
Efficacy
When administered along with standard childhood vaccines,2 the efficacy of
RTS'S in infants aged 6 to 12 weeks (at first vaccination) against
clinical and severe malaria was 31% and 37%,3 respectively, over 12 months
of follow-up after the third vaccine dose.4 Insecticide-treated bed nets
were used by 86% of the trial participants, which demonstrated that RTS,S
provided protection beyond existing malaria control interventions. The
efficacy observed with RTS,S last year in children aged 5-17 months of age
against clinical and severe malaria was 56% and 47%, respectively.
Follow-up in this Phase III trial will continue and is expected to provide
more data for analyses to better understand the different findings between
the age categories.
Dr. Abdulla added: "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
analyze 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."
Safety
There was no increase in overall reporting of serious adverse events5
(SAEs) between the infants vaccinated with the RTS,S malaria vaccine
candidate and infants in the control group, which received a comparator
vaccine. Side effects primarily included local injection site reactions,
which were less frequent following RTS,S vaccinations compared to the
DTP-HepB/Hib vaccine. Fever was reported more frequently following RTS,S
vaccinations than the control vaccine group (30.6% versus 21.1% of vaccine
doses, respectively).
Two new cases of meningitis were reported in the 6-12 week-old infant age
category in addition to the 9 reported last year; one in the RTS,S group
and one in the control vaccine group. Further analysis revealed a
bacterial cause of the meningitis in 7 of the 11 cases.
Sir Andrew Witty, CEO, GSK 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."
The vaccine is being developed in partnership by GSK and MVI, together
with prominent African research centres1. 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.
Looking ahead
Follow-up in this Phase III trial will continue to provide more data for
analyses to better understand the different findings between the age
categories. These data and analyses should also provide insights into the
vaccine candidate's efficacy in different malaria parasite transmission
settings. 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 data and analyses will inform the regulatory submission strategy and,
if the required regulatory approvals are obtained and public health
information, including safety and efficacy data from the Phase III
programme, is deemed satisfactory, the World Health Organization (WHO) has
indicated that a policy recommendation for the RTS,S malaria vaccine
candidate is possible as early as 2015, paving 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.
GSK and MVI are committed to making this vaccine available to those who
need it most, should it be approved and recommended for use. 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.
Notes to Editors
About RTS,S
RTS,S is a scientific name given to this malaria vaccine candidate6 and
represents the composition of this vaccine candidate. RTS,S aims to
trigger the immune system to defend against Plasmodium falciparum malaria
parasite when it first enters the human host's bloodstream and/or when the
parasite infects liver cells. It is designed to prevent the parasite from
infecting, maturing, and multiplying in the liver, after which time the
parasite would re-enter the bloodstream and infect red blood cells,
leading to disease symptoms. In the Phase III efficacy trial, RTS,S is
administered in three doses, one month apart. A booster dose administered
18 months after the third dose is also being studied in the trial.
The vaccine, based on a protein first identified in the laboratory of Drs
Ruth and Victor Nussenzweig at New York University, was invented,
developed, and manufactured in laboratories at GSK Vaccines in Belgium in
the late 1980s and initially tested in US volunteers as part of a
collaboration with the US Walter Reed Army Institute of Research.
In 2001, the MVI entered into partnership with GSK to study the vaccine
candidate's ability to protect young children in sub-Saharan Africa. Over
time, the partnership expanded to include the 11 African research centres
and, in some instances, associated scientific institutions from Europe and
the United States.
With more than US$200 million in grant monies from the Bill & Melinda
Gates Foundation, MVI contributes financial, scientific, managerial, and
field expertise to the development of RTS,S. GSK takes the lead in the
overall development of RTS,S and has invested more than $300 million to
date and expects to invest more than $200 million before the completion of
the project.
About the study
The first complete set of results in children aged 5 to 17 months and
combined data for severe malaria in the first 250 cases from those aged 6
weeks to 17 months were published in the New England Journal of Medicine
in November 2011. The Phase III trial has been designed in consultation
with the appropriate regulatory authorities and the WHO. It is conducted
in accordance with the highest international standards for safety, ethics,
and clinical practices and is overseen by an independent data safety
monitoring committee.
About GSK Vaccines
GlaxoSmithKline Vaccines is active in vaccine research and development.
Headquartered in Belgium, GSK Vaccines has 14 manufacturing sites
strategically positioned around the globe. Of the 1.1 billion doses of our
vaccines we distributed in 2011, over 80% went to developing countries,
which include the least developed, low- and middle-income countries.
GlaxoSmithKline - one of the world's leading research-based pharmaceutical
and healthcare companies - is committed to improving the quality of human
life by enabling people to do more, feel better and live longer. For
further information, please visit www.gsk.com<http://www.gsk.com>.
The PATH Malaria Vaccine Initiative (MVI) is a global program established
at PATH through an initial grant from the Bill & Melinda Gates Foundation.
MVI's mission is to accelerate the development of malaria vaccines and
ensure their availability and accessibility in the developing world. MVI's
vision is a world free from malaria. For more information, please visit
www.malariavaccine.org<http://www.malariavaccine.org>.
PATH is an international nonprofit organization that transforms global
health through innovation. PATH takes an entrepreneurial approach to
developing and delivering high-impact, low-cost solutions, from lifesaving
vaccines and devices to collaborative programs with communities. Through
its work in more than 70 countries, PATH and its partners empower people
to achieve their full potential. For more information, please visit
www.path.org<http://www.path.org>.