EMA Releases Positive Opinion for GSK’s Malaria Vaccine

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has announced a positive scientific opinion for GlaxoSmithKline’s (GSK’s) malaria candidate vaccine Mosquirix (RTS,S) for use outside of the European Union (EU) in children aged 6 weeks to 17 months.

While other vaccines tackle viruses or bacteria, RTS,S has been designed to prevent malaria caused by the Plasmodium falciparum parasite, which is prevalent in sub-Saharan Africa (SSA) and also protects against hepatitis B. In 2013, there were an estimated 584,000 deaths from malaria with approximately 90% of these occurring in SSA, and 83% in children under the age of five in SSA, the World Health Organization (WHO) reports.

RTS,S aims to trigger the body’s immune system to defend against the 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, after which time the parasite would re-enter the bloodstream and infect red blood cells, leading to disease symptoms, GSK reports in a statement.

Limited effectiveness
Data from a clinical trial conducted in seven African countries showed that Mosquirix provides modest protection against Plasmodium falciparum malaria in children in the 12 months following vaccination. The vaccine was effective at preventing a first or only clinical malaria episode in 56% of children aged between 5–17 months and in 31% of children aged 6–12 weeks. The efficacy of the vaccine decreased after one year. The safety profile of the vaccine was considered acceptable, EMA reports.

CHMP concluded that despite its limited efficacy, the benefits of Mosquirix outweigh the risks in both age groups studied and the benefits of vaccination may be particularly important among children in high-transmission areas in which mortality is very high.

Because the studies showed that Mosquirix does not offer complete protection, and the protection it provides decreases in the longer term, EMA states that established protective measures, such as insecticide-treated bed nets, should continue to be used in addition to the vaccine.

Next steps in development
The vaccine was submitted to EMA under a regulatory procedure (Article 58) that allows EMA to assess the quality, safety, and efficacy of a medicine or vaccine and its benefit-risk balance, although it will not be marketed in the EU. EMA reports that the CHMP worked closely with WHO and regulatory authorities from the relevant countries and applied the same rigorous standards as for medicines to be marketed within the EU.

The EMA approval was a pre-requisite for a WHO policy recommendation for the use of Mosquirix in vaccination programs. WHO will consider additional factors not addressed by EMA including feasibility of implementation, affordability, cost-effectiveness, and the public health value of the vaccine in relation to other available malaria control measures and vaccines. WHO will provide its recommendations on use of Mosquirix by November 2015. Regulators in the countries where the vaccine will be used will decide on licensing in their jurisdictions.

RTS,S, which was developed in partnership with the PATH Malaria Vaccine Initiative (MVI), is the first candidate vaccine for the prevention of malaria to reach this milestone, GSK reports. RTS,S was created in 1987 by scientists working at GSK laboratories. Early clinical development was done in collaboration with the Walter Reed Army Institute for Research. In January 2001, GSK and PATH, with grant monies from the Bill & Melinda Gates Foundation to PATH, entered into a public-private partnership to develop an RTS,S-based vaccine for infants and young children living in malaria-endemic regions in sub-Saharan Africa.

GSK reports the company has invested more than $365 million to date and expects to invest a further $200 to $250 million until development is completed. Between 2001 and the end of 2014, the MVI, supported by grants from Bill & Melinda Gates Foundation, invested more than $200 million to advance the RTS,S project.

In a press statement, GSK noted that the company has committed to a not-for-profit price for RTS,S; if approved, the price of RTS,S would cover the cost of manufacturing the vaccine with a return of around 5% that will be reinvested in research and development for second-generation malaria vaccines, or vaccines against other neglected tropical diseases.

Sources: GSK and European Medicines Agency