GlaxoSmithKline reports results from ongoing Phase III trial show malaria vaccine
candidate, RTS,S* reduces the risk of malaria by half in African
children aged 5 to 17 months.
18 October 2011. Half
the world’s population is at risk of malaria which is responsible for
close to 800,000 deaths each year, most of whom are children under five
in sub-Saharan Africa
First results from a large-scale Phase III trial of RTS,S, published online today in the New England Journal of Medicine (NEJM),
show the malaria vaccine candidate to provide young African children
with significant protection against clinical and severe malaria with an
acceptable safety and tolerability profile. The results were announced
today at the Malaria Forum hosted by the Bill & Melinda Gates
Foundation in Seattle, Washington.
5 to 17 month-old children
The trial,
conducted at 11 trial sites in seven countries across sub-Saharan
Africa, showed that three doses of RTS,S reduced the risk of children
experiencing clinical malaria and severe malaria by 56% and 47%,
respectively. This analysis was performed on data from the first 6,000
children aged 5 to 17 months, over a 12-month period following
vaccination. Clinical malaria results in high fevers and chills. It can
rapidly develop into severe malaria, typified by serious effects on the
blood, brain, or kidneys that can prove fatal. These first Phase III
results are in line with those from previous Phase II studies.
The widespread coverage of insecticide-treated bed nets (75%) in this
study indicated that RTS,S can provide protection in addition to that
already offered by existing malaria control interventions.
6 to 12 week-old infants
The trial is
ongoing and efficacy and safety results in 6 to 12 week-old infants are
expected by the end of 2012. These data will provide an understanding of
the efficacy profile of the RTS,S malaria vaccine candidate in this age
group, for both clinical and severe malaria.
Combined data in 6 to 12 week-old infants and 5 to 17 month-old children
An
analysis of severe malaria episodes so far reported in all 15,460
infants and children enrolled in the trial at 6 weeks to 17 months of
age has been performed. This analysis showed 35% efficacy over a
follow-up period ranging between 0 and 22 months (average 11.5 months).
Long-term efficacy
The RTS,S malaria vaccine
candidate is still under development. Further information about the
longer-term protective effects of the vaccine, 30 months after the third
dose, should be available by the end of 2014. This will provide
evidence for national public health and regulatory authorities, as well
as international public health organisations, to evaluate the benefits
and risks of RTS,S.
Safety
The overall incidence of serious
adverse events (SAEs)** in this trial was comparable between the RTS,S
candidate vaccine (18%) recipients and those receiving a control vaccine
(22 %)
Differences in rates of SAEs were observed between the vaccine groups
for specific events, such as seizures and meningitis, and were higher in
the malaria vaccine group. Seizures were considered to be related to
fever and meningitis was considered unlikely to be vaccine-related.
These events will continue to be monitored and additional information
about the safety profile of the RTS,S malaria vaccine candidate will
become available over the next three years.
Tsiri Agbenyega, a principal investigator of the trial and Chair of the Clinical Trials Partnership Committee, said:
“The publication of the first results in children aged 5 to 17 months
marks an important milestone in the development of RTS,S. These results
confirm findings from previous Phase II studies and support ongoing
efforts to advance the development of this malaria vaccine candidate.
Having worked in malaria research for more than 25 years, I can attest
to how difficult making progress against this disease has been. Sadly,
many have resigned themselves to malaria being a fact of life in Africa.
This need not be the case. Renewed interest in malaria by the
international community, and scientific evidence such as that we are
reporting today, should bring new hope that malaria can be controlled.”
Andrew Witty, CEO, GSK said: “These data bring
us to the cusp of having the world’s first malaria vaccine, which has
the potential to significantly improve the outlook for children living
in malaria endemic regions across Africa. The addition of a malaria
vaccine to existing control interventions such as bed nets and
insecticide spraying could potentially help prevent millions of cases of
this debilitating disease. It could also reduce the burden on hospital
services, freeing up much needed beds to treat other patients who often
live in remote villages, with little or no access to healthcare. Today’s
results are a testament to the dedication and tenacity of many
scientists, led at GSK by Jean Stéphenne and his vaccine team, including
Joe Cohen, the co-inventor of RTS,S, in partnership with many others
from across the world. Development is however only half the task, but
GSK remains committed to further research into malaria and most
importantly, to ensuring that this vaccine will reach those who need
it.”
Christopher Elias, president and CEO of PATH , said:
“This trial represents a powerful example of the high-quality science
that is moving us toward controlling and someday potentially eliminating
malaria. The results made public today are encouraging and certainly
something to feel good about, but let’s also remember the human
dimension. The PATH Malaria Vaccine Initiative’s mission is to deliver a
vaccine to the children of Africa so that instead of carrying near
lifeless babies to crowded pediatric wards, mothers will carry their
infants past noisy school playgrounds to bustling immunization clinics.
Today, we are an important step closer to realizing that vision, and we
look forward to continuing our drive, together with our partners, to
bring this vaccine home to the children of Africa.”
Bill Gates, co-chair of the Bill & Melinda Gates Foundation, said:
“A vaccine is the simplest, most cost-effective way to save lives.
These results demonstrate the power of working with partners to create a
malaria vaccine that has the potential to protect millions of children
from this devastating disease.”
The vaccine is being developed in partnership by GSK and the PATH
Malaria Vaccine Initiative (MVI), together with prominent African
research centers. The partners are all represented on the Clinical
Trials Partnership Committee, which is responsible for the conduct of
the trial. Major funding for clinical development comes from a grant by
the Bill & Melinda Gates Foundation to MVI. An extended team of
organisations continues to work on RTS,S, including scientists from
across Europe, North America and Africa. Should it be approved by
regulatory authorities and recommended by the World Health Organisation
(WHO), it will be used for African children, who are most at risk from
the disease. Successful development of an effective vaccine to be used
alongside other measures such as bed nets and anti-malarial medicines
would represent a decisive step toward sustained malaria control.
The impact of the RTS,S Phase III trial extends beyond the vaccine being
researched. The trial has made a considerable contribution to many of
the African communities that host the trial sites through improved
healthcare and hospital facilities. Research capacity at many of the
research centres has been strengthened through the training of staff,
provision of state-of-the-art laboratories, equipment, and construction
of new facilities. This enhanced capacity bodes well for the centres to
expand further their leadership in developing remedies for malaria and
other infectious diseases for years to come.
Looking ahead
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 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.
If the required public health information, including safety and efficacy
data from the Phase III programme, is deemed satisfactory, the 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.
Notes to Editors
About RTS,S
RTS,S is a scientific name given
to this malaria vaccine candidate 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, and from re-entering the
bloodstream and infecting red blood cells, at which point the affected
person would begin to show symptoms of the disease.
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 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.
In 2001, the PATH Malaria Vaccine Initiative (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 clinical development and in the interactions with
regulatory agencies and has invested more than $300 million to date and
expects to invest another $50-100 million before the completion of the
project.
About the study
This is one of the final
stages in evaluating the efficacy and safety of the vaccine candidate in
infants and young children on a large scale before regulatory file
submission.
The partners in the development of RTS,S have placed the utmost emphasis
on the health and safety of the study participants. 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.
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
GlaxoSmithKline Biologicals - (GSK Biologicals),
GlaxoSmithKline’s vaccines business, is one of the world’s leading
vaccine companies and a leader in innovation. The company is active in
vaccine research, development and production with over 30 vaccines
approved for marketing and 20 more in development - both in the
prophylactic and therapeutic fields. Headquartered in Belgium, GSK
Biologicals has 14 manufacturing sites strategically positioned around
the globe. In 2010, GSK Biologicals distributed 1.43 billion doses of
vaccines to 179 countries in both the developed and the developing
world.
Through its accomplished and dedicated workforce, GSK Biologicals
applies its expertise to the discovery of innovative vaccines that
contribute to the health and well-being of people of all generations
around the world.
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.
PATH is an international non-profit 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.
*contains QS-21 Stimulon® adjuvant licensed from Antigenics Inc, a
wholly owned subsidiary of Agenus Inc. (NASDAQ: AGEN), MPL and
liposomes.
**A serious adverse event refers to any medical event that occurs during
the course of a clinical trial and that results in death, is life
threatening, requires inpatient hospitalization, or results in a
persistent or significant disability or incapacity needs, regardless of
whether the SAE is considered to be caused by the study vaccination. All
SAEs are reported to regulatory authorities.
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