Dismay at the effectiveness of GSK’s malaria vaccine

The expectations and anticipation regarding the world’s first potential malaria vaccine have been dealt a blow after trial results demonstrated that the protection the vaccine offers, can significantly diminish and disappear altogether over time, disappointing researchers who had high hopes for it.

Developed by British pharmaceutical giant GlaxoSmithKline (GSK), the new vaccine is currently only referred to as ‘RTS,S’. Scientists state that full data from final-stage trials which include 15,000 children, are expected by the end of 2014. However, early results from the vaccine are not encouraging and expose the difficulties in creating a vaccine that offers full protection from a deadly disease such as malaria that claims the lives of more than 650,000 children every year – the most ‘at risk’ group in regards to mosquito bites.

The vaccine has been primarily engineered to help babies aged between six to 12 weeks and in a large-scale phase III trial that was carried out last year, only a third of babies aged within this range were prevented from becoming ill after being administered the new vaccine. Moreover, the protection was lower than what was evident in older children.

Microsoft co-founder Bill Gates, worth an estimated £40bn, was one of the backers behind the research, and after those results emerged last year he commented: “The efficacy came back lower than we had hoped, but developing a vaccine against a parasite is a very hard thing to do.”

Christopher Plowe, a malaria researcher at the University of Maryland School of Medicine in the United States, who was not involved in the RTS,S trial, also spoke on the findings last year, saying: “The results are kind of disappointing because we’d all like to see a malaria vaccine that has closer to 80 percent or 100 percent efficacy.”

Results of the latest data were published this week in the New England Journal of Medicine. Although the RTS,S vaccine was found to have a rate of protecting peaking at 53%, after an average of merely eight months, the level of protection had declined at an alarming rate.

Ally Olotu of the Kenya Medical Research Institute (KEMRI) Wellcome Trust Research Programme in Kenya, who led the follow-up study, said: “It was a bit surprising to see the efficacy waned so significantly over time. In the fourth year, the vaccine did not show any protection.”

A GSK spokesperson commented on the latest results, stating that because they were derived from a small, mid-stage trial, they did not “provide definitive answers about the duration of protection or how the vaccine candidate works in different malaria transmission settings.”

Phillip Bejon, a researcher at the KEMRI-Wellcome Trust programme, was involved with the study and he said in spite of the decreasing effectiveness, “there is still a clear benefit to the vaccine.”

Bejon added: “Many of the children (in Africa) will experience multiple episodes of clinical malaria infection, but overall we found that 65 cases of malaria were averted over the four-year period for every 100 children vaccinated. We now need to look at whether offering a vaccine booster can sustain efficacy for longer.”

New single dose Malaria drug in development

A recently discovered compound from the aminopyridine class, code named MMV390048 has shown potent activity against multiple points in the malaria parasite’s life cycle.

This means that it not only has the potential to become part of a single dose cure, but it might also be able to block transmission of the parasite from person to person. On this basis it was selected by the MMV Expert Scientific Advisory Committee (ESAC), for further development, making it the first compound researched on African soil to enter pre-clinical development in partnership with MMV.

According to the World Health Organisation (WHO), each year between 149 million and 274 million people contract malaria, and about 655,000 people die from it. Here at Medical Specialists News we only reported earlier this month, on how many Britain’s are contracting malaria whilst abroad, due to not taking or not completing an anti-malarial course of medication.

The fact MMV390048 could be part of a single dose cure could prove effective, as current anti-malarial drugs need to be taken before, during and after entering a malaria zone. Malarone for example, needs to be taken two days before entering a malaria zone, for the duration of the holiday and then for seven days after returning home.

However other anti-malarial drugs need to be taken up to three weeks before travel and up to four weeks on return. This is where some Britain’s have slipped up and ended up suffering from malaria, because they have failed to start the course early enough or they have failed to finish the course. Obviously this is where a single dose cure such as MMV390048 could prove invaluable.

The aminopyridine series was initially identified by Griffith University scientists in Australia, as part of MMV’s extensive malaria screening campaign of around 6 million compounds. A team of scientists from the University of Cape Town’s Drug Discovery and Development Centre in South Africa, led by Professor Kelly Chibale, then scrutinised and explored the antimalarial potential of the series further.

With parasitological and pharmacological support from the Swiss Tropical and Public Health Institute and Monash University, respectively, Professor Kelly’s team selected the most promising compounds from the series to be optimized and re-tested. In just 18 months the team had identified and developed a candidate, suitable for preclinical development.