Drug researcher W. Ripley Ballou remembers the moment he realized that GlaxoSmithKline Plc’s experimental malaria vaccine might save millions of lives.
Ballou, 56, was a U.S. Army colonel at Walter Reed Army Institute of Research in Washington in 1996 when the vaccine, called Mosquirix, was tested in seven volunteers who were bitten by malaria-infected mosquitoes. The shot protected six of them.
“That was really a major `Aha’ moment for us,” said Ballou, who was collaborating with a company that later merged with Glaxo. “That made up for 10 years of failure.”
It took eight more years of development and testing before scientists were ready to conduct a large-scale trial of the vaccine. London-based Glaxo and its partners will begin a $100 million study of Mosquirix later this year, vaccinating 16,000 children in seven African countries. If the results are positive, the drug could be on the market as soon as 2011, making it the first vaccine against the deadly disease.
This year malaria will infect 300 million to 500 million people in Africa, Asia, Latin America and parts of Europe, according to the Web site of the Bill & Melinda Gates Foundation, the world’s largest charitable fund. At least 1 million will die, most of them children under the age of five in sub-Saharan Africa.
Emphasis on Prevention
Vaccines were a backwater of scientific research a decade ago as pharmaceutical companies focused on drugs that could generate $1 billion or more in annual sales. The strategy emphasized treating conditions such as high cholesterol that affect people in developed countries. The cholesterol drug Lipitor, made by New York-based Pfizer Inc., had worldwide sales of $12.7 billion last year, a fourth of the company’s revenue.
While Lipitor costs about $120 a month, according to the Web site drugstore.com, vaccines sometimes sold for as little as $10 for a treatment needed no more than once a year.
As drugmakers struggled to develop new products and recover sales lost to generic medicines, they turned to vaccines, which are harder to copy than other treatments.
Wyeth, based in Madison, New Jersey, showed that vaccines could help drive profits. Sales of Prevnar, Wyeth’s drug to prevent pneumonia, totaled $2.4 billion last year, 13 percent of the company’s total drug sales.
“Suddenly, we had some novel vaccines, such as Prevnar, in areas with high unmet needs,” said Hedwig Kresse, a drug industry analyst at London-based Datamonitor Plc. “High unmet needs means you can command high prices.”
Glaxo shares rose 37 pence, or 3.2 percent, to 1,183 pence at the close of London trading, giving the company a market value of 62.5 billion pounds ($124 billion).
Worldwide Attention
Fighting malaria has become a top public health priority. The Seattle-based Bill & Melinda Gates Foundation has spent more than $860 million on prevention and treatment programs. An additional $1.6 billion in grants over the past five years came from the Geneva-based Global Fund to Fight AIDS, Tuberculosis and Malaria.
The financial commitments have spurred malaria research. Mosquirix is competing against 30 or so experimental vaccines, most still in development at academic research centers. Crucell NV, based in Leiden, the Netherlands, and Sanofi-Aventis SA, France’s biggest drugmaker, are working on their own versions. None of the rival products has progressed farther than the start of preliminary clinical trials.
“With the exception of Mosquirix, there’s no possibility of one coming on the market within five or six years,” said Kevin Marsh, professor of tropical medicine at Oxford University.
Parasites Attack
A bite from an infected mosquito injects its victim with Plasmodium parasites, which multiply in the bloodstream and attack the liver. Patients experience fever, chills and flu-like symptoms. Left untreated, the disease can overwhelm the body’s immune system, causing shock, anemia and organ damage.
“It outwits the human immune response by changing itself,” said Marsh, who now serves as director of the Kenya Medical Research Institute/Wellcome Trust program in Kilifi, Kenya.
“It can become more severe and cause damage to the brain, lungs and body,” he said. “Someone who has no immunity at all may go into a coma and die.”
The malaria parasite has about 5,000 genes, compared with fewer than 100 in most viruses. This makes developing a vaccine as difficult as creating one to protect against cancers.
“This is a complex parasite with many thousands of genes,” said Glaxo molecular biologist and vice president Joe Cohen, 64. “It is very well adapted to the host.”
Army Experiments
Walter Reed researchers turned to scientists at SmithKline & French, which later became part of Glaxo, in 1983 for access to a new technology that genetically engineered E. coli bacteria to produce large amounts of a protein found in the malaria parasite. Army scientists used the protein to make malaria vaccines to protect soldiers.
They spent 20 years producing a dozen vaccines, all of which failed.
Ballou experienced some of the disease’s effects in the late 1980s when, as a young Army captain, he and other soldiers were injected with an experimental malaria vaccine. The volunteers allowed a cupful of infected mosquitoes to bite their forearms in tests at Walter Reed. All but one person in Ballou’s group became ill.
“I was sicker than a dog,” said Ballou, a fourth- generation Army officer and a dropout from the U.S. Military Academy at West Point who retired from the military in 1999. “It was a very unpleasant disease.”
Overcoming Obstacles
SmithKline moved its Philadelphia-based vaccine unit to Rixensart, Belgium, in 1987. There, the molecular biologist Cohen worked with scientists who invented a precursor of Mosquirix, called RTS.
The RTS vaccine initially worked in two of eight volunteers exposed to malaria. Cohen, ignoring a series of failures and skepticism from his peers, then combined a protein from the Plasmodium parasite with another from the Hepatitis-B virus.
“It was encouraging and indicated to us that we were on the right track and that modifying the formulation might very well lead us to success,” said Cohen, who now heads Glaxo’s malaria, tuberculosis and HIV vaccine research in Rixensart. “I had nothing at all, just an idea.”
His idea became the vaccine RTS,S, a combination of the proteins RTS and S. An adjuvant, or chemical additive that boosts the body’s immune response, was later included and the vaccine was named Mosquirix. The 1996 test at Walter Reed showed its promise. The one volunteer who became infected was treated.
`Fantastic Breakthrough’
“It was an incredibly fantastic breakthrough,” said Cohen, whose persistence kept Glaxo’s malaria vaccine project alive.
Now Cohen, an Egyptian-born Jew who lived in France and trained at New York’s Brooklyn College and Albert Einstein Medical College, could see the potential for his effort to save millions of lives.
The U.K.’s government-funded Medical Research Council began testing Mosquirix in adults in Gambia in 1998.
By 2002, the studies had expanded to include adolescents in Mozambique. One clinical trial, published in the British medical journal The Lancet in October, showed that infants between 10 and 18 weeks old had no ill effects from taking Mosquirix.
The shot also reduced new malaria infections in the first three months by 65 percent.
Not Good Enough
That isn’t good enough to interest the U.S. military, which needs 99 percent effectiveness for soldiers, said Ballou, who now works for the Gates foundation.
Doctors treating malaria patients in Africa have a different perspective.
“If you can reduce 50 percent of the burden, then you reduce a lot of the burden faced by families and the health facilities,” said Marcel Tanner, director of the Swiss Tropical Research Institute in Basel, Switzerland.
Cohen and his colleagues hope to know within three years whether they’ve won the race to produce an effective vaccine.
Creating Mosquirix was “a huge milestone,” said Alan Brooks, director of policy for the Malaria Vaccine Initiative, a charity based in Bethesda, Maryland, that has collaborated with Glaxo since 2001. “This is the best hope for a first generation product.”
To contact the reporter on this story: Andrea Gerlin in London at agerlin@bloomberg.net
RESOURCE/SOURCE:http://www.freedomsphoenix.com/Find-Freedom.htm?At=035314 on Thursday July 3, 2008.
