A VACCINE AGAINST MALARIA: GSK BIOLOGICALS’ RTS,S

A pivotal efficacy trial of RTS,S, the world’s
most clinically advanced malaria vaccine candidate, is now underway in seven
African countries: Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique and
Tanzania. The trial, which is expected to involve up to 16,000 children, is on
schedule, with more than 5,000 children already enrolled, researchers announced
Tuesday at the 5th Multilateral Initiative on Malaria Pan-African Malaria Conference. 

Developing a vaccine against malaria, a
scientific challenge for decades, is critical to defeating the disease. A
vaccine would complement existing interventions, such as bed nets and effective
drug therapies. GlaxoSmithKline Biologicals’ (GSK Bio) RTS,S is the first
malaria vaccine candidate to demonstrate significant efficacy during early
development to warrant Phase III testing. It is the leading vaccine candidate
in the global effort by the PATH Malaria Vaccine Initiative (MVI) to develop a
malaria vaccine.

“A malaria vaccine could help save countless
lives and redefine the future for Africa’s children,” said Dr. Patricia Njuguna,
RTS,S principal investigator (KEMRI-Wellcome Trust, Kilifi, Kenya) and chair of
the Clinical Trials Partnership Committee, a collaboration of African research
institutions, MVI, and GSK Bio that is leading the clinical development of
RTS,S. “Communities all across Africa are dedicated to this future and are
participating to ensure that we develop a vaccine with an acceptable safety and
efficacy profile.”

RTS,S is the first vaccine designed primarily
for use in Africa, where malaria kills more than 800,000 people every year, the
majority of them children under the age of five. By conducting the trial in
seven different countries across Sub-Saharan Africa, researchers will be able
to evaluate the vaccine candidate’s efficacy in a variety of settings, with
diverse patterns of malaria transmission. For example, some trial sites are
located in areas where there is a year-round threat of malaria, while others
experience only seasonal transmission.

All of the research centers were chosen for
their track record of world-class clinical research, strong community relations
and commitment to meeting the highest international ethical, medical, clinical
and regulatory standards.

“This is a tremendous moment in the fight
against malaria and the culmination of more than two decades of research,
including 10 years of clinical trials in Africa,” said Dr. Joe Cohen,
co-inventor of RTS,S and Vice President of R&D, Vaccines for Emerging
Diseases and HIV, at GSK

Biologicals. “The Phase III trial is a huge
undertaking that depends on effective coordination between researchers, regulators,
families and communities. Everyone involved has invested significant energy and
resources to pave the way for what could become the world’s first malaria
vaccine.”

Recent Phase II studies showed that RTS,S
reduced clinical episodes of malaria by 53 percent over an eight-month
follow-up period. Findings from a Phase II trial initiated in 2002 and
conducted with more than 2,000 children in southern Mozambique, published in
the medical journal The Lancet in 2004 and 2005, showed that RTS,S was
efficacious for at least 18 months in reducing clinical malaria by 35 percent,
and severe malaria by 49 percent.[i]^{, [ii]}
 In addition, RTS,S was shown
to have a promising safety and tolerability profile when used alongside the
World Health Organization’s (WHO) standard infant vaccines.

The Phase III trial

The Phase III trial will evaluate the vaccine’s
efficacy in two groups of children. One group, aged 6 to 12 weeks, will be
vaccinated as part of their regular schedule of infant immunizations; the
second group includes children aged 5 to 17 months. The vaccine profile is
intended primarily for infants, as they and children under the age of five are
the most vulnerable to malaria.

“This is the largest trial ever conducted in
Africa of a vaccine specifically designed for use with African children. We
have great appreciation for the families and children participating,” said Dr.
Salim Abdulla, director of the Ifakara Health Institute, Tanzania, which is participating in the Phase III
trial. “Development of RTS,S across Africa has
strengthened our research capacity, a legacy that will far outlast the trials.”

Each country hosting a study site has undertaken
independent reviews to ensure the trial meets national safety, ethical and
legal standards for medical research. In addition, an independent data and
safety monitoring board oversees the entire trial with support from local
safety monitors. The trial has been designed in consultation with
appropriate regulatory authorities in the European Union, the United States and
African countries, in conjunction with the WHO. 

Looking
ahead

If the Phase III program progresses as expected,
RTS,S could be submitted for regulatory review under Article 58 as early as
2012. Article 58 is a special review procedure that allows the European
Medicines Agency (EMEA), in close collaboration with the WHO, to issue a
scientific opinion regarding the quality, the efficacy and the safety of a
medical product that is intended for use exclusively outside the European
Union.

Under current plans, the RTS,S vaccine candidate
would be submitted to regulatory authorities in 2012 based on efficacy
in children 5-17 months of age. Additional safety and immunogenicity data
from the infant population will be submitted soon thereafter, followed by
efficacy data for infants once available. Depending on the final clinical profile
of the vaccine and the timetable of the regulatory review process, the first vaccine
introduction could take place over the next three to five years.

 “GSK’s approach is to make every effort
possible to accelerate the availability of this life-saving vaccine,” said Mr.
Jean Stéphenne, President and General Manager, GlaxoSmithKline
Biologicals.  “Ever conscious of the burden of malaria, we have no time to
lose and we will exhaust every avenue at our disposal. This is our commitment
as a company.”

MVI, the WHO and US Agency for International Development
developed the Malaria Vaccine Decision-Making Framework to help countries
prepare to make decisions related to future adoption of a malaria vaccine and
thereby avoid unnecessary delay between the recommendation for use of a vaccine
and its availability in low-income countries. GSK and MVI are already working
with malaria-affected countries and international institutions to ensure that,
if successful, a malaria vaccine will be readily available and affordable to
those who need it most.