As Trials Advance for a Malaria Vaccine, Policy Makers Urged to Plan for Its Use

Abstract

AS THE FIRST PROMISING MALARIA vaccine makes its way through phase 3 clinical trials in subSaharan Africa, stakeholders’ greatest fears go beyond the possibility that the vaccine may fail to meet safety and efficacy goals. They worry that even if the vaccine is licensed, inadequate planning for its distribution could leave it to languish in warehouses. “After decades of research and tens of millions of dollars invested . . . it would be scandalous if this vaccine just sits on the shelf,” said Yvette Collymore, MA, of the nonprofit PATH Malaria Vaccine Initiative (MVI), during a recent Washington, DC, conference. MVI and the vaccine’s creator, GlaxoSmithKline (GSK) Biologicals, partnered in 2001 to develop the vaccine for infants and young children in sub-Saharan Africa. But the origins of the vaccine, known as RTS,S, date back to 1984 when GSK collaborated on preclinical studies with researchers at the Walter Reed Army Institute of Research in Silver Spring, Md. Human trials in adults in the United States and Belgium began in 1992. The first African trials were launched in 1995. Since then, several published studies have shown that the vaccine has a favorable safety and efficacy profile. A phase 2b trial with 340 infants in Tanzania showed that the vaccine reduced the risk of Plasmodium falciparum infection by 65% (Abdulla S et al. N Engl J Med. 2008;359[24]:2533-2544). RTS,Senteredphase3clinical trials in 2009. Eleven sites in 7 countries will enroll 16 000 infants and children, constituting the largest malaria vaccine trial to date. As of late September, about 12 500 children were enrolled: nearly 9000 in a cohortaged6to12weeksandmore than 3000 in a second cohort aged 5 to 17 months. Efficacy data from the older cohort of children are expected in late 2011 and shouldbe followedupayear laterbydata from the younger children, said MarieChantalUwamwezi,MSc, senior regulatoryaffairsscientistatGSK.The30-month follow-updataareexpectedat theendof 2014. The earliest the vaccine could be available for general use would be 2015. Collymore said that efforts began in 2006 to prepare policy makers in Africa forthestepsneededtobringamalariavaccine to the public. “Policy makers need data, and they need it well before this intervention is available; otherwise, this decision can take decades,” she said. Someof thecountries thatmay implement immunization once a malaria vaccine is available are using a decisionmaking tool based on the World Health Organization’s (WHO’s) guidelines for the introduction of any new vaccine. “It looks at the disease burden and the existing interventions, because [the vaccine] will be used alongside other interventions,” Collymore said. “It looks at the efficacy and safety of the vaccine and the sociocultural context of countries where it will be introduced: what communities think about malaria, what some of their beliefs are, and what they think about immunizations.” Tsiri Agbenyega, MD, principal investigator at a clinical trial site in Ghana, said that as phase 3 results become available, clinical data provided for the licensing process will describe not only safety and efficacy, but also the immunogenicity and reactogenicity of RTS,S when given with other vaccines through a WHO program. Safety and efficacy data from HIV-infected children who receive the vaccine also will be provided. Even with phase 3 trial results pending,GSKhasbeeninvolvedforthelastfew years in licensure discussions with African regulatory authorities as well as officials at the WHO and the European Medicines Agency (EMA), which evaluates medical products. “We have an innovative, streamlinedregulatorystrategy toensure licensureandexpediteaccess,” said Uwamwezi. If phase 3 trials are successful, GSK would ask the EMA to review the vaccine and certify it as safe and effective. The certification would pave the way for GSK to apply to African regulatory authorities for marketing authorization. “We can’t overemphasize the major societal, economic, and public health impact this vaccine would have on subSaharan Africa,” said Agbenyega.