After nearly 25 years in development, the world’s most promising malaria vaccine disappointed. The results of Phase III clinical trials released in November showed the experimental malaria vaccine candidate, known as RTS,S, protected about one-third of infants between six and 12 weeks – failing the criteria set by the World Health Organization (WHO) to be deemed viable.
The RTS,S trial was not the success the public health community was hoping for – especially given that earlier trials showed 55% efficacy in children between 5 and 17 months. But it is still too early to give up on the vaccine, and more detailed results from the trial are set for release in 2014. As David Kaslow, director of the PATH Malaria Vaccine Initiative (which is behind RTS,S), told Think Africa Press, “It’s fair to say that higher efficacy would be preferable, but the facts remain that RTS,S demonstrated an acceptable safety profile, and was shown to provide protection to infants beyond that provided by bed nets”.
Nevertheless, with few other potential vaccines on the horizon, this set back could finally spur the public health donors to do something they have been failing to do for more than two decades: get more innovative in funding research and development.
The development of RTS,S was funded by a $500 million donation from the Bill and Melinda Gates Foundation, GlaxoSmithKline and the US government. Much of the disappointment with the results stems from the fact that, even though 655,000 people die every year from malaria, that level of funding does not come along often. Indeed, as far back as the early-1990s, public health officials coined the term ‘the 10/90 gap’ to describe the situation whereby only 10% of international spending on vaccine research and development goes toward those diseases affecting 90% of the world’s population, such as malaria, HIV and tuberculosis. Though the percentages have varied over time, the discrepancy remains.
“The market of big pharmaceuticals has failed to meet the needs of poor people, who have no ability to purchase drugs”, explains Unni Karunakara, International President of Médecins Sans Frontières (MSF). Furthermore, the distress over the RTS,S results is compounded by knowledge that every piece of bad news reinforces the existing impression that malaria vaccine research is a bad investment.
That is one of the reasons MSF used the money it won from the 1999 Nobel Peace Prize to start the Drugs for Neglected Diseases initiative (DNDi). This programme promotes research into drugs for a range of illnesses including malaria, sleeping sickness and Chagas. This is not a traditional function of an organisation like MSF. But in the absence of more funding for research and development, says Karunakara, “it is a role that we’ve over time had to take on, because no one else is doing it”. MSF and its partners can ensure a certain level of research is maintained until big pharmaceutical companies start to weigh in. This will only happen once a market large enough to attract their attention has emerged.
That is what Advanced Market Commitments (AMCs), in contrast to traditional donor-subsidised efforts, were created to do. The idea behind AMCs is relatively straightforward: donors and developing countries put out a call for a vaccine. Ahead of any research, development or manufacturing, governments commit to buying a certain amount – with the cost heavily subsidised by donors – if the vaccine meets certain predetermined standards. That guarantees the pharmaceutical company a set market and a good price for any drugs it develops. Once a fixed number of sales is reached and the pharmaceutical company has turned its profit, it is then obligated to continue selling long-term at an affordable price, or license the technology to someone who would.
Such plans had been floating around since the mid-2000s, but it was not put into practice on any significant scale until 2009, when five countries and the Gates Foundation created an AMC to fight pneumococcal. This bacterium, which can lead to pneumonia and meningitis, kills almost one million young people every year. It is also easily preventable – vaccines existed, they were just not being distributed. Under the AMC, donors committed to pay a guaranteed sum of $1.5 billion to manufacturers who agreed to create and sell the vaccines at no more than $3.50 a dose, over ten years. The GAVI Alliance is working with developing countries to facilitate uptake of the vaccine.
And it’s working. The pilot project is on track to prevent more than 1.5 million childhood deaths by 2020. The idea was to test “whether the technical features of the original academic concepts of an AMC could be realised in practice”, a GAVI spokesperson told Think Africa Press. “The pilot AMC was demonstrated to be an effective mechanism for accelerating the development, manufacturing capacity and country uptake of much-needed vaccines.”
What an AMC has not yet shown, however, is whether it can stimulate pharmaceutical companies to start early-stage development of vaccines. In the case of pneumococcal, a vaccine already existed, and the AMC simply compelled companies to scale up manufacturing. But a malaria AMC, for instance, would require companies to develop and test from scratch an extraordinarily complicated vaccine – as the RTS,S results underscored. “The biggest challenge with an early-stage vaccine is creating a market big enough that it offers companies a sufficient return on a risky investment,” says Owen Barder, a senior fellow at the Center for Global Development and one of the originators of the AMC concept. As yet, there are no vaccines against any human parasitic diseases, like malaria.
But if enough donors are willing to guarantee the money required to justify the risk, then vaccines for malaria – or HIV, sleeping sickness, Chagas – will no longer seem like such bad investments. With several competing vaccines in the pipeline, one disappointing trial will no longer be enough to potentially derail research into a particular disease.
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