NEW ORLEANS, Dec. 8 /PRNewswire/ -- 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
(NYSE: 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 Vaccines(1)
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 Children(2)
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)-Wellcome
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-Wellcome 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 a 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 Kilifi District Hospital, 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 Bagamoyo District Hospital 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 http://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
http://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 http://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 randomized controlled phase I/IIb trial. Lancet 2007 Nov
3;370(9598):1543-51. Epub 2007 Oct 18.
