Vaccine development needs global alliance
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Who has saved the most lives in human history? Claims can be made for various scientific pioneers and political leaders, but few are as strong as that of Edward Jenner, inventor of the world’s first successful vaccine — for smallpox.
That innovation alone has, by some estimates, prevented more than 500m deaths since the English doctor first tested it on his gardener’s eight-year-old son in 1796. But that number is many times greater when all the other vaccines that flowed from his breakthrough are included.
Smallpox remains the only infectious disease in history to have been completely eradicated, but global health leaders hope there will soon be a second. Worldwide cases of polio — which can lead to irreversible paralysis in children — have been reduced from 350,000 in 1988 to just 74 last year by mass immunisation programmes. A new, safer polio vaccine currently being rolled out across 155 countries by the UN-backed Global Polio Eradication Initiative is being billed as a final push against the disease.
The successes against smallpox and polio are the clearest dividends of Jenner’s discovery that an infectious disease can be prevented if the immune system has been exposed beforehand to a biological agent that mimics the pathogen. But many other potential killers, from measles and typhoid to whooping cough and meningitis, have been beaten back by vaccines. Immunisation has been the biggest factor behind childhood mortality rates halving worldwide since 1990.
Seth Berkley, chief executive of Gavi, the global alliance that supplies subsidised vaccines to low-income countries, says the health benefits are matched by their economic impact. For every dollar spent on childhood immunisation, he says, $16 of future health costs are averted. When the value of people living longer, more productive lives is included, the gain increases to $44.
“That’s a greater return on investment than for public infrastructure, pre-school education and community health workers combined,” says Dr Berkley, whose organisation supports the immunisation of two out of every five children born worldwide.
Yet, for all the progress, the next steps remain fraught with difficulties. One in five children around the world still does not receive a full course of even the most basic vaccines, resulting in the death of 1.5m children under the age of five every year — equivalent to one death every 10 seconds — from preventable diseases such as pneumonia and diarrhoea due to rotavirus.
Weak health infrastructure in many parts of the developing world is a problem and many health activists blame manufacturers such as Pfizer and GlaxoSmithKline for pricing their drugs too high. Dr Berkley says that through negotiations with drugs companies Gavi has lowered the cost of a full course of childhood vaccinations in the countries it supports to less than $30, compared with $930 in the US.
A $7.5bn financing round last year — including $1.5bn each from the Bill & Melinda Gates Foundation and the UK government and a further $1bn from the US government — has boosted Gavi’s capacity. It aims to immunise an extra 300m children in addition to the 500m it has already reached.
Widening access to existing vaccines is only part of the challenge. Just as important is discovering and developing new ones to tackle diseases such as HIV and hepatitis C, for which no vaccines currently exist, and improving the partially effective ones for influenza and tuberculosis.
There are some causes for optimism. The first vaccine for dengue fever — a mosquito-borne virus that causes an estimated 500,000 hospitalisations and more than 12,000 deaths a year across tropical and subtropical regions — was launched this year by Sanofi, the French pharmaceuticals group.
The first malaria vaccine, developed by GSK, also received a green light from European regulators last year and at least one of the three Ebola vaccines that were rushed into clinical trials during the recent epidemic in west Africa appears to be effective.
But Ebola also exposed weaknesses in vaccine capabilities. The vaccine that advanced furthest during the epidemic, known as VSV-EBOV, had been discovered by Canadian scientists more than a decade earlier. Lack of commercial or public funding meant it languished on a laboratory shelf until the emergency in west Africa prompted Merck & Co to acquire and develop it.
This was not the first time in recent years that the world has found itself wishing for a new vaccine. From swine flu to severe acute respiratory syndrome (Sars) and its cousin Middle East respiratory syndrome (Mers), a spate of outbreaks have exposed our continued vulnerability to infectious diseases. Zika, the mosquito-borne virus linked with birth defects in Latin America, is just the latest example.
None has yet turned out to be on the scale of the 1918 Spanish flu — which infected a third of the world’s population and killed tens of millions — but the scares have been serious enough to prompt a push to improve global co-ordination on vaccine development.
The issue was high on the agenda when political and business leaders met at the World Economic Forum in Davos in January. Thomas Breuer, chief medical officer of GSK’s vaccines unit, detects “a real sense of urgency” to come up with a better model. “It was lucky that GSK and other companies had [vaccine] candidates in early development for Ebola,” he says. “With Zika, no one has ever worked on it. There are no candidates, no regulatory pathways.”
Dr Breuer says GSK has talked to several governments and international organisations about the potential to increase research and development into vaccines for diseases where there is not enough commercial incentive for investment. “The world needs to make some educated guesses about the future threats and commit resources to preparing for them,” he says.
A paper in the New England Journal of Medicine last July called for the creation of a $2bn global vaccine fund — financed by governments, foundations, pharma companies and other industries — to fill the R&D gaps that market forces have neglected.
One the authors of that paper was Jeremy Farrar, director of the London-based Wellcome Trust, the world’s second-largest medical charity after the Gates Foundation. He says Ebola and Zika are harbingers of an era in which pandemics will occur more frequently and spread more rapidly around an increasingly interconnected world.
“We have to accept there are going to be a number of these emergencies over the next 20-30 years,” he says. “We can’t waste a year each time searching around for [vaccine] candidates and working out how to make them.”
More investment is not the only requirement. Dr Farrar says increased co-operation and communication between academics, companies and governments is at least as important — and he believes this is starting to happen.
By sharing information, researchers can accelerate each other’s work where progress is occurring and identify areas in need of more attention. “If we know what everyone is doing, we can cover all the known bases and have platforms in place to deal with the unknowns when they come along,” Dr Farrar says.