Positive Phase II results for GSK’s malaria vaccine

PRLog (Press Release) – Oct 22, 2007 – Results from a Phase I/IIb trial of GlaxoSmithKline’s malaria vaccine, Mosquirix (RTS,S/AS02D), published in The Lancet, indicate that it is safe, well tolerated and immunogenic in African infants. Other Phase II studies are ongoing, but these results “help pave the way for a pivotal Phase III trial of what could be the first malaria vaccine for infants and young children in Africa,” said Dr Christian Loucq, director of the PATH Malaria Vaccine Initiative.

GSK plans to begin Phase III testing in the second half of 2008, with a view to filing for registration in 2011. The large-scale trials are expected to involve some 10,000 children at 10 locations in seven countries in sub-Saharan Africa.

The study, conducted by the Hospital Clinic of the University of Barcelona at the Manhiça Health Research Centre (CISM) in Mozambique, enrolled 214 infants aged 10-18 weeks. They were randomly assigned to receive three doses either of Mosquirix or GSK’s hepatitis B vaccine, Engerix-B, at ages 10, 14, and 18 weeks, as well as routine immunisation vaccines given at ages 8, 12, and 16 weeks.

The primary endpoint was safety. Mosquirix’s safety and reactogenicity profiles were similar to those observed with the standard vaccines. Secondary endpoints included immunogenicity and analysis of new Plasmodium falciparum infections during a follow-up period. Efficacy against new infections was found to be 65% during a three-month follow-up after the third dose, while episodes of clinical malaria were reduced by 35% over a six-month period following the first dose.

This efficacy data is consistent with an estimate of 45% reduction in new infections reported in a 2004 Phase IIb trial in Mozambique among 2,022 children 1-4 years old. However, GSK emphasises that the primary endpoint of the latest study was safety, and efficacy against severe disease was not included due to its small size.

The trials are being run by an international public-private collaboration, including African research institutions and scientists in five countries, GSK, and the PATH Malaria Vaccine Initiative. GSK has invested $300 million so far to develop the vaccine. PATH received a grant of $107.6 million from the Bill & Melinda Gates Foundation in 2005 to expand clinical evaluation of RTS,S.

Mosquirix uses a recombinant protein that fuses part of the P falciparum circumsporozoite protein (CSP) with hepatitis B surface antigen. Combined with a proprietary adjuvant, RTS,S induces 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 collaboration with the US Walter Reed Army Institute of Research.