Dengue vaccine disappoints in clinical trial
LONDON, England, Wednesday September 19, 2012 – The results of a recent clinical trial of a vaccine against dengue fever have indicated that the mosquito-borne disease is unlikely to be eradicated in the Caribbean, or anywhere else, anytime soon.
In development by French drug manufacturer Sanofi SA, the world's most advanced vaccine against dengue proved only 30 percent effective in a large clinical trial in Thailand. On the upside, researchers said it showed for the first time that a safe vaccine was possible.
Well below the 70 percent-plus efficacy researchers had anticipated at the start of the company-funded trial, the disappointing outcome was due to the vaccine's failure to protect against one type of dengue virus, which turned out to be the most prevalent in Thailand at the time of the study.
Dengue fever, also known as "breakbone fever", is a threat to nearly three billion people and is caused by four types of virus, none of which confers immunity from the others.
The outlook had originally been optimistic for the Thai trial, given that dengue belongs to the same virus class as yellow fever and Japanese encephalitis, both of which are controlled with highly effective existing vaccines.
It nevertheless appears that making a mixed dengue vaccine containing four different virus strains can produce uneven results, illustrating the complexity of a disease that scientists have been trying to combat for over 70 years.
Sanofi disclosed in July that the Thai dengue study showed efficacy against three of the four strains, without giving details. The full findings were published online last week in the The Lancet medical journal.
Jean Lang, Sanofi's head of dengue vaccine development, said that, despite the disappointment, the Phase IIb study involving 4,002 Thai children was encouraging, given the protection provided against three out of four of the virus strains.
Efficacy was around 60 percent against dengue virus type 1 and 80-90 percent against types 3 and 4. A single dose of the vaccine proved roughly as good as three doses, moreover.
"This is a milestone, but we need to wait for the results of two large Phase III efficacy trials to have a better understanding of the vaccine," Lang said.
Sanofi is conducting final-stage Phase III trials with 31,000 participants in Latin America and Asia, and attention will now focus on results for these ongoing Phase III trials, with any commercial launch in 2015 or later.
Other drug companies are also working on dengue vaccines but Sanofi's product is several years ahead. The French group has already invested 350 million euros in a new French factory to make its vaccine.
An accompanying commentary on the study in The Lancet said it was possible that a vaccine against three out of four virus strains might still combat dengue effectively, since severe disease is caused by a second infection.
Dengue is spread by the bite of the Aedes aegypti mosquito, and in the past 50 years there has been a 30-fold jump in cases. The World Health Organisation (WHO) officially puts infections at 50-100 million a year, though many experts think this assessment from the 1990s is an underestimate.
Most patients survive dengue, but it is estimated to kill about 20,000 every year, many of them children.