Eagerly awaited results from tests on Sanofi's dengue fever vaccine candidate have been published. The plan is to market the vaccine by 2015. But experts still disagree about its usefulness.
And…finally, the new results are here: the French pharmaceutical company Sanofi Pasteur has announced its hotly anticipated results from a clinical dengue vaccine trial in Latin America.
"Second large-scale phase III study successfully meets primary endpoint with overall vaccine efficacy of 60.8 percent," the press release reads.
Researchers have long awaited these results.
In July, Sanofi published the results of the first part of the clinical study in Asia. The substance, called CYD-TDV, showed an efficacy of 56.5 percent against dengue infections in children aged 2 to 14.
But for some, it was no reason to be cheerful. Experts said the vaccine's efficacy could only be assessed based on results from a clinical study in Latin America.
More than 20,000 children aged 9 to 16 in Brazil, Colombia, Mexico, Honduras and Puerto Rico took part in the study.
Phase III is the final and most expensive part in vaccine development and occurs before a company can attempt to register a vaccine and bring it to market.
Only the most advanced vaccine candidates reach this phase. In the case of dengue fever, Sanofi's CYD-TDV is the first vaccine candidate to make it to phase III trials.
"Not perfect, but promising"
An efficacy of 60.8 percent means it could prevent more than halve the number of dengue infections.
The trial also shows the vaccine reduced the number of severe dengue cases, involving hospitalization, by 80.3 percent.
Each year, an estimated 500,000 people fall ill with severe dengue - known as dengue hemorrhagic fever - and require hospitalization.
Dengue can lead to death and many of those who contract it are children.
The findings from the latest trial "are totally consistent with the Asian multi-centre trial," says Annelies Wilder-Smith, researcher at Nanyang Technological University in Singapore. Wilder-Smith was involved in an earlier phase of developing the potential vaccine, but not in the recent phase III study.
"In fact, these data from [Latin America] are even more encouraging."
They show a higher overall efficacy and are encouraging results for one specific subtype of the dengue virus, she says.
"It is not a perfect vaccine, but a promising vaccine."
Not all dengue is the same
There are four subtypes of dengue - serotype 1, 2, 3 and 4 - that co-exist in endemic countries.
People can get infected with any one, or all of them. Immunity against one serotype does not provide immunity against any of the the other three.
But the prevalence of the various serotypes differs from region to region.
And so the situation in Asia is completely different from that in Latin America and the Caribbean, where the second trial took place.
In the Asian study, Sanofi Pasteur's vaccine protected quite well against serotypes 3 and 4, with an efficacy of 75 percent.
Protection against serotype 1 was 50 percent, and against serotype 2 the efficacy rate was only 35 percent.
In Latin America, the results were similar.
The vaccine protects against serotypes 3 and 4 with an efficacy of 74 and 77.7 percent, and against serotype 1, it is 50.3 percent effective. Protection against serotype 2 in Latin America is marginally better than in Asia, with an efficacy ratet of 42.3 percent.
Jonas Schmidt-Chanasit, head of the virus diagnostics department at Bernhard-Nocht Institute for Tropical Medicine in Hamburg, says "the results are not exactly brilliant."
Back in July, Schmidt-Chanasit highlighted the fact that the vaccine's efficacy varied from serotype to another, and he warned this could be dangerous.
Vaccination would potentially protect against several dengue subtypes, while at the same time strengthening the one against which protection was low.
As result, it was felt the vaccine could end up worsening the situation in dengue-endemic countries.
It was an opinion which Wilder-Smith rejected.
"Forty and 50 percent protection against some of the serotypes is very sobering," Schmidt-Chanasit says on the latest results, adding the vaccine would need at least 80 or 90 percent efficacy.
Most of the data, though, have yet to be published.
Sanofi Pasteur says it plans to present the data at the American Society of Tropical Medicine and Hygiene Annual Meeting at the beginning of November.
But Schmidt-Chanasit is still not happy. He points out that the vaccine needs three shots to achieve any efficacy at all - and says this would be impractical in developing countries.
The price of the vaccine is another question.
Guillaume Leroy, head of Sanofi's dengue vaccine project, declined an offer to comment on pricing for the news agency, Reuters.
Sanofi Pasteuer is said to have invested more than 1.3 billion euros in its dengue projects, comprising of two decades of research.
"With this vaccine, there is a lot of money involved," Schmidt-Chanasit says.
The Reuters report suggest Sanofi expects to submit regulatory applications in the first quarter of 2015.
The company aims to sell the first doses of the vaccine in the second half of 2015, with a dedicated plant outside Lyon, in southeastern France, expected to produce up to 100 million doses per year.
But Schmidt-Chanasit says the countries in which dengue fever is endemic will need to make a thorough cost-benefit analysis.
"Instead of putting billions of dollars into this vaccine, the appropriate countries might do better to use this money to improve their health systems."