The first study to test GlaxoSmithKline’s (GSK) investigational RTS,S/AS02 malaria vaccine in African infants serves as the first proof of concept in this population that the vaccine has a promising safety and tolerability profile and reduces malaria parasite infection and clinical illness due to malaria, according to a paper published today online in The Lancet.
The primary objective of the study was to assess whether RTS,S could be safely administered to the age group most vulnerable to severe disease and death from malaria. For the study, 214 infants between 10 and 18 weeks of age were enrolled. The vaccine candidate’s safety and reactogenicity profiles were similar to those observed with standard EPI vaccines given to infants, including comparable local pain and swelling.
The study reports that vaccine efficacy against new infections was 65 percent over a three-month follow-up period after the infants received all three doses of the vaccine. The results also showed that the vaccine reduced episodes of clinical malaria by 35 percent over a six-month follow-up period starting after the first dose.
This efficacy data is consistent with the estimate of 45 percent reduction in new infections reported in a 2004 trial in Mozambiqueamong children one to four years old. However, the clinical malaria results from this study should be viewed in the context that the primary endpoint was safety. The secondary endpoints are efficacy against infection and against clinical malaria. Efficacy against severe disease was not included due to the smaller size of the safety study. Although a large-scale Phase III study will be required to definitively determine the efficacy of the vaccine, the data from this trial are encouraging.
This Phase II trial was conducted by the Manhiça Health Research Centre (CISM) in Mozambiqueby scientists from the Hospital Clinic of the Universityof Barcelonaand the Mozambique Ministry of Health. The PATH Malaria Vaccine Initiative, which is a key partner in the clinical development of RTS,S, provided funding for the trial based on a grant from the Bill & Melinda Gates Foundation. RTS,S was invented and first developed by GSK scientists in 1987 and the company has overseen its development ever since.
“We have shown for the first time that a vaccine can reduce the risk of malaria infection in young African infants exposed to intense P. falciparum transmission,” said CISM’s Pedro Alonso, MD, PhD, senior author of The Lancet article, principal investigator of the study, and head of the Barcelona Center for International Health Research (CRESIB) at the Hospital Clinic of the University of Barcelona. “These tantalizing and unprecedented results further strengthen the vision that a vaccine may contribute to the reduction of the intolerable burden of disease and death caused by malaria.”
“We have invested over US$300 million to develop an effective vaccine with a safety profile that could allow it to be given to millions of infants and children in Africa,” said Jean Stéphenne, president of GSK Biologicals, the vaccine division of GSK. “Our collaboration with the PATH Malaria Vaccine Initiative and CISM, which dates back to 2001, demonstrates how public-private partnerships can help overcome critical health problems in Africa. Anticipating licensure, we are already working with our partners and with international donors to ensure that this vaccine is affordable and available to all who need it.”
“While other Phase II studies of this vaccine candidate are underway, this study helps pave the way for a pivotal Phase III trial of what could be the first malaria vaccine for infants and young children in Africa,” added Christian Loucq, MD, director of the PATH Malaria Vaccine Initiative. “The world urgently needs a safe and effective vaccine to reduce the suffering malaria causes.”
The RTS,S vaccine uses a recombinant protein created by GSK scientists that fuses part of the P.falciparum circumsporozoite protein (CSP) with hepatitis B surface antigen. Combined with a proprietary GSK Adjuvant System, RTS,S induces the production of antibodies and T cells that interfere with the ability of the malaria parasite to infect humans. Early development of RTS,S was undertaken by GSK in close collaboration with the US Walter Reed Army Institute of Research (WRAIR).
RTS,S will require a few more years of clinical investigation. The trials are being implemented by an international public-private collaboration, including African research institutions and scientists in five countries, GSK, and the PATH Malaria Vaccine Initiative. PATH received a grant of $107 million from the Bill & Melinda Gates Foundation in 2005 to expand clinical evaluation of RTS,S.
If the results continue to look promising, testing would move on to a Phase III trial, which is currently slated to begin in the second half of 2008. A successful Phase III trial could result in submission to regulatory authorities in 2011.
The trial was approved by Mozambican National Bioethics Committee, the Hospital Clinic of Barcelona Ethics Review Committee and the PATH Human Subjects Protection Committee. It was conducted with the oversight of an independent Local Safety Monitor and a Data Safety Monitoring Board.