PATH partners with the Mahidol Oxford Tropical Medicine Research Unit on first study of the RTS,S malaria vaccine in Asia

PATH/MVI: Preeti Singh, Washington, DC/USA, mobile: +1 703-862-2515, psingh@burness.com
Kelsey Mertes, Seattle/USA, mobile: +1 301-312-7844, kmertes@path.org.

PATH's Malaria Vaccine Initiative (MVI) is collaborating with the Mahidol Oxford Tropical Medicine Research Unit (MORU) and GSK to assess the safety and immunogenicity of the RTS,S/AS01 malaria vaccine candidate (RTS,S) in combination with antimalarial drugs. The Phase 2 trial being conducted in Bangkok, Thailand, under the collaboration is the first to evaluate RTS,S in an Asian population.

The primary aims of the Bangkok study are to determine whether coadministering antimalarial drugs with RTS,S will affect the vaccine candidate's ability to create an immune response and to assess the safety of RTS,S in Thai adults, as well as the safety of coadministration. The Phase 2 clinical trial is an initial step toward determining whether RTS,S could be used as part of targeted efforts to eliminate malaria in Southeast Asia and help slow the spread of multidrug-resistant Plasmodium falciparum malaria parasites—the species of the malaria-causing parasite most deadly to humans.

Professor Sasithon Pukrittayakamee and colleagues from Mahidol University have enrolled 190 Thai adult volunteers in the clinical trial. Trial participants will be closely monitored over the course of six months to provide data regarding how safe and effective RTS, S might be in this population when administered in combination with antimalarial drugs.

An approved malaria vaccine, added to currently used interventions, could help to eliminate and eventually eradicate the P. falciparum parasite in Southeast Asia's Greater Mekong Subregion (GMS), if such a vaccine were shown to be sufficiently effective. Initial studies of an alternate dosing regimen of RTS,S showed that reducing the dosage of the third vaccination and delaying its administration could increase its impact. Results of a US study published in 2016 showed this alternate regimen to be approximately 87 percent efficacious against infection three weeks after immunization (compared to 63 percent for the standard monthly full-dose regimen). The immunogenicity of this alternate regimen will be assessed through the Bangkok study.

Efforts that aim to eliminate malaria-causing parasites—combining malaria case management by village health workers, vector control, and mass antimalarial drug administration—are currently being tested in selected areas throughout Southeast Asia's GMS. Mass administration of antimalarial drugs can interrupt malaria transmission for limited time periods. Adding mass vaccination campaigns using an approved malaria vaccine may achieve the longer-lasting interruptions of parasite transmission needed to eliminate P. falciparum from the area and prevent reintroduction.

Adding an approved malaria vaccine to the suite of tools in the fight against malaria could also help slow the emergence of parasite resistance to antimalarial drugs. In the GMS, the P. falciparum parasite is developing resistance to the drug treatment most commonly used against it—artemisinin-based combination therapies (ACTs). If these multidrug-resistant parasite strains spread, it could increase the risk of serious illness and death in the affected regions of the world with the greatest malaria burden.

This emerging threat heightens the need for additional tools, and the Phase 2 clinical trial in Bangkok, Thailand, is a first step toward better understanding if RTS,S has a role to play in this fight.

"This is an exciting time for everyone working on RTS,S " said Dr. Ashley Birkett, Director of PATH's Malaria Vaccine Initiative. "Not only is it moving into pilot introduction for use in the population most at risk of succumbing to malaria—African children—but also into early-stage testing to see if an alternative regimen with modified dosage and schedule could have an impact on adults in a part of the world where RTS,S has never been evaluated and where malaria poses a serious threat."

RTS,S was created in 1987 by scientists working at GSK laboratories. Early clinical development was conducted in collaboration with the Walter Reed Army Institute for Research. In January 2001, GSK and PATH's Malaria Vaccine Initiative, with grant monies from the Bill & Melinda Gates Foundation to PATH, entered into a public-private partnership to develop RTS,S for infants and young children living in malaria-endemic regions in sub-Saharan Africa. RTS,S has undergone a series of studies, including a Phase 3 efficacy and safety trial that involved over 15,000 infants and young children and 11 sites in seven African countries. This trial concluded in early 2014. Since then, the data generated on the candidate vaccine have been reviewed by two leading health authorities. First, RTS,S received a positive scientific opinion from the European Medicines Agency, Europe's regulatory authority, in July 2015. Then, after a consultation process, the World Health Organization (WHO) issued its position paper in January 2016, recommending pilot implementation. RTS,S will be administered to at least 360,000 children in selected areas of three countries in Africa—Ghana, Kenya, and Malawi—starting in 2018, through a pilot implementation program coordinated by WHO. The vaccine will be administered in a four-dose regimen, with the first dose given as soon as possible after the age of five months, with the following two doses at least four weeks apart, and the fourth dose administered close to a child's second birthday, 15 to 18 months after dose three.

As with most vaccines, RTS,S aims to trigger the body's own immune system to defend against disease, in this case, malaria. Specifically, RTS,S is designed to prevent the malaria parasite from infecting, maturing, and multiplying in the liver, after which the parasite would normally reenter the bloodstream and infect red blood cells, leading to disease symptoms.

PATH's Malaria Vaccine Initiative (MVI) accelerates malaria vaccine development and catalyzes timely access in endemic countries, toward a world free from malaria. Standing at the intersection of malaria and immunization, MVI is part of PATH's Center for Malaria Control and Elimination and PATH's Center for Vaccine Innovation and Access. Learn more at www.malariavaccine.org or http://sites.path.org/cvia/.

The Mahidol Oxford Tropical Medicine Research Unit (MORU) develops effective and practical means of diagnosing and treating malaria and other neglected diseases such as melioidosis, typhus, TB and leptospirosis. MORU was established in 1979 as a research collaboration between Mahidol University (Thailand), Oxford University (UK) and the UK's Wellcome Trust. To learn more, please visit www.tropmedres.ac.

GSK—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.

Posted August 9, 2017.