Data in infants and young children reinforce case for phase III
trial of RTS,S/AS
Results published online today in the New England Journal of
Medicine revealed that the world's most clinically advanced malaria vaccine
candidate provides both infants and young children with significant protection
against malaria. Two separate phase II trials reaffirmed earlier study results
and support the ongoing efforts, pending regulatory approvals, to launch the
phase III
study of GlaxoSmithKline (GSK) Biologicals' RTS,S/AS vaccine candidate across
Africa.1 ,2
In infants, data show for the first time that the vaccine
candidate can be administered as part of existing African national immunization
programs. In children aged 5 to 17 months, the candidate RTS,S/AS01 reduced the
risk of clinical episodes of malaria by 53 percent over an eight-month
follow-up period and was shown to have a promising safety profile. The studies
were conducted in Kenya
and Tanzania
and were presented today at the American Society for Tropical Medicine and
Hygiene (ASTMH) annual meeting.
RTS,S/AS is the leading candidate in a global effort
coordinated by the PATH
Malaria Vaccine Initiative (MVI) to develop a malaria vaccine. Malaria kills
almost one million people each year-most of them infants and young children in Africa,
the intended recipients for this vaccine candidate.3
"Today's study results strongly show that our investments in
developing malaria vaccines are beginning to pay dividends," said Christian
Loucq, MVI director. "We are closer than ever before to developing a malaria
vaccine for children in Africa.
History has shown that vaccines are the most powerful tool to control and
eliminate infectious diseases. Clearly, the world urgently needs a safe and
effective vaccine to win the war against this terrible disease."
The studies published today build on previous findings
indicating the efficacy of RTS,S/AS, including a phase 2 trial, published in
The Lancet in 2007, that demonstrated "proof of concept" that RTS,S/AS could
prevent malaria infection in infants.4
"The vaccine works alongside standard infant vaccines of
WHO's Expanded Program of Immunization (EPI), has a favorable safety profile,
and has consistently shown a significant efficacy level. We can begin to foresee
the difference this scientific breakthrough could make in the lives of millions
of African children who suffer and die from this disease year after year," said
Joe Cohen, a co-inventor of the vaccine and vice-president of Research &
Development, Emerging Diseases & HIV at GSK Biologicals. "The energy and
motivation levels are at an all-time high, as the partnership finalizes
preparations to launch the historic phase III
trial early next year."
Infant Study: Effective Co-Administration with EPI Vaccines1
The infant study enrolled 340 infants under 12 months of age
in Tanzania and found that RTS,S/AS02, when administered at 8, 12, and 16 weeks
of age with a commonly used childhood vaccine, did not interfere with the
protective immune responses to each of the vaccine components. The childhood
vaccine contained antigens for Diphtheria (D), Tetanus (T), whole-cell
pertussis (Pw) and haemophilus influenzae B (Hib). In countries where a malaria
vaccine is needed most, the current immunization schedule for infants, called
the WHO Expanded Program on Immunization (EPI), would provide an optimal
delivery platform.
Researchers evaluated the safety and immune responses when
administering the RTS,S/AS02 vaccine in conjunction with an EPI schedule. It
was a randomized double-blind trial with participants simultaneously receiving
either RTS,S/AS02 and DTP w/Hib as well as oral polio vaccine; or a hepatitis B
vaccine and DTP w/Hib as well as oral polio vaccine.
Additionally, the study reported 65 percent reduction against
first infection from malaria in those infants who received three doses of the
RTS,S/AS02 vaccine and were followed over a six-month period. This study builds
upon results published in October 2007 in The Lancet, which found a similar
level of efficacy for RTS,S/AS02 when it was given in a staggered fashion with
the administration of DTPw/Hib vaccine.4
"This finding has a very strong implication for protecting
infants: RTS,S/AS efficacy data are very encouraging when administered
alongside the childhood vaccines now widely in use and those vaccines maintain
their desired efficacy alongside RTS,S," said Salim Abdulla of the Ifakara
Health Institute of the Tanzanian Ministry of Health. Abdulla led a team that
included researchers from the Swiss Tropical Institute and the London School of
Hygiene and Tropical Medicine, GSK Biologicals, and MVI.
Child Study: 53% Efficacy Against Clinical Malaria in
Children2
The other trial enrolled 894 children 5-17 months old in
both Kenya
and Tanzania.
It was designed to evaluate the safety and efficacy of the RTS,S/AS, combined
with another GSK's proprietary Adjuvant System, coded AS01. The study was a
double-blind randomized clinical trial in which children received either three
doses of the RTS,S/AS01 vaccine candidate or a rabies vaccine.
It found that the RTS,S/AS01 formulation reduces clinical
malaria episodes by 53 percent for up to an average of eight months. Earlier
studies in Mozambique
using RTS,S formulated with a different GSK Adjuvant System (AS02) demonstrated
35 percent efficacy against clinical disease for 18 months among children 1-4
years old. Researchers concluded that these study results support the use of
RTS,S/AS01 for upcoming Phase 3 trials.
"These findings build a solid case for phase III
testing, which the partners in this endeavor are looking forward to starting in
the near future," said Philip Bejon of Kenya Medical Research Institute
(KEMRI)-Welcome Collaborative Research Programme and the Centre for Tropical
Medicine, University
of Oxford,
the study's lead author.
The team for the efficacy trial of RTS,S/AS01 in young
children comprised researchers from the KEMRI-Welcome Collaborative Research
Programme (Kilifi,
Kenya),
the National Institute for Medical Research (Tanzania),
the Joint Malaria Programme (Korogwe,
Tanzania),
and other institutions in collaboration with GSK and the MVI.
About RTS,S/AS
GSK and the PATH
Malaria Vaccine Initiative signed a public-private partnership agreement in
2001 to pursue pediatric clinical development of RTS,S/AS in Africa.
To advance the development program, African research centers in five countries,
and collaborating institutions, joined with the partnership.
Pending approvals by national regulatory agencies and ethics
committees, a multi-center phase III
efficacy trial is on track to start in early 2009. The trial will seek to
confirm and evaluate with precision the vaccine's efficacy, including duration,
and will continue to closely monitor safety.
The vaccine was invented, developed and manufactured in
laboratories at GSK Biologicals' headquarters in Belgium
in the late 1980s and initially tested in US volunteers as part of collaboration
with the US Walter Reed Army Institute of Research.
Funding for the development of this vaccine candidate has been
made possible through a US$107.6 million grant from the Bill & Melinda
Gates Foundation to the PATH
Malaria Vaccine Initiative. GSK has invested approximately $300 million to date
and expects to invest another $50-100 million before the completion of the
project.
The clinical development of RTS,S/AS is led by the Clinical
Trial Partnership Committee, a collaboration of leading African research
institutes, Northern academic partners, MVI and GSK with support from the
Malaria Clinical Trial Alliance.
# # #
About KEMRI-Wellcome Research Programme
The KEMRI-Wellcome Research Programme is an internationally
renowned research centre tackling malaria and other important diseases in Kenya.
Safeguarding the health of young African children and their families is the
primary motivation of research. The Programme is fully integrated into the
Kenyan research infrastructure, through its close relationship with KEMRI
(Kenya Medical Research Institute). In Kilifi, the Programme is embedded within
KilifiDistrictHospital,
building its research programmes around local medical infrastructure and
contributing to healthcare delivery. Researchers are also committed to engaging
with the local community, to discuss their research and why it is being carried
out. The Programme is located at sites in Kilifi, an hour's drive north of Mombasa
on the coast of Kenya,
and in the capital Nairobi.
For more information, please visit http://www.kemri-wellcome.org.
About the Joint Malaria Programme,
Tanzania
The Joint Malaria Programme (JMP) is a joint collaborative
link between the National Institute for Medical Research (NIMR) in Tanzania,
Kilimanjaro Christian Medical Centre (KCMC) in Tanzania,
London School of Hygiene and Tropical Medicine (LSHTM) in the UK,
and the Centre for Medical Parasitology (CMP) at the University
of Copenhagen
in Denmark.
Its mission is to conduct health research to alleviate disease burden in Tanzania.
The Korogwe trial site, established in 2002 under NIMR Tanga Centre, has a
staff of around 70. The site aims to be a center of excellence in clinical and
biomedical research. Korogwe is located in the Tanga region of Tanzania,
an area that has seen a recent decline in malaria rates. Korogwe has a
Demographic Surveillance System (DSS)
under NIMR Tanga Centre for malaria intervention trials. For more information,
please visit http://196.45.36.203/Pages/projects/about.html.
About the Bagamoyo Branch of the Ifakara Health Institute
The Ifakara Health Institute (IHI),
formerly IHRDC, is an autonomous, non-profit, district-based health research
and resource institute headquartered in Ifakara,
Tanzania.
The Bagamoyo unit was established as an extension of the Ifakara Health
Institute in 2005. It is dedicated to promoting effective solutions to
important public health issues through research, training and service support
for community development. It has distinguished itself in a short time period
as a leading clinical trial site and has made a significant positive impact on
the community through the improvements it has brought to the BagamoyoDistrictHospital
and the peripheral health facilities in the vicinity of the hospital. IHI
was registered as a Tanzanian Trust in 1996 under the leadership of the Board
of Trustees chaired by Ministry of Health. Other members of the Board include
National Institute for Medical Research, Swiss Agency for Development and
Cooperation, Swiss Tropical Institute, Commission for Science and Technology,
Regional Medical Officer for Morogoro, Managing Trustee of African Malaria
Intervention Network, Muhimbili University College of Health Sciences, Economic
and Social Research Foundation, INDEPTH, Representatives of Regional
Administration and Local Government. For more information, please visit
http://www.ihi.or.tz.
About GSK Biologicals
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
company information, please visit www.gsk.com/media.
GSK Biologicals (GSK Bio), one of the world's leading
vaccine manufacturers, is headquartered in Rixensart,
Belgium,
where the majority of GlaxoSmithKline's activities in the field of vaccine
research, development and production are conducted. In 2006, GSK Bio
distributed more than 1.1 billion doses of vaccines to 169 countries. Of these
doses, seventy-five percent of these went to the developing world.
Approximately 136 million were doses of combination pediatric vaccines which
protect the world's children from up to six diseases in one vaccine.
About the PATH
Malaria Vaccine Initiative (MVI)
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.
Founded in 1977, PATH
is an international, nonprofit organization that creates sustainable,
culturally relevant solutions, enabling communities worldwide to break
longstanding cycles of poor health. By collaborating with diverse public- and
private-sector partners, PATH
helps provide appropriate health technologies and vital strategies that change
the way people think and act. PATH's
work improves global health and well-being. For more information, please visit
www.path.org.
1 Abdulla S, Oberholzer R, Juma O, et al. Safety and immunogenicity
of RTS,S/AS02D malaria vaccine
in infants. N Engl J Med 2008;359:2533-44.
2 Bejon P, Lusingu J, Olotu A, et al. Efficacy of
RTS,S/AS01E: clinical malaria in 5 to 17 month old children. N Engl J Med
2008;359:
3 World Health Organization. World Malaria Report
2008, Sept 2008. http://malaria.who.int/wmr2008. Last accessed: Nov 2008
4 Aponte JJ, Aide P, Renom M, et al. Safety of the
RTS,S/AS02D candidate malaria vaccine in infants living in a highly endemic
area of Mozambique:
a double blind randomised controlled phase I/IIb trial. Lancet 2007 Nov
3;370(9598):1543-51. Epub 2007 Oct 18.
