An experimental vaccine against dengue fever being developed by Sanofi proved about 60 percent effective in its second large clinical trial. The results could clear the way for the introduction of the world’s first inoculation against the disease, which is mosquito-borne and becoming an increasing threat.
Sanofi, a French drug company, said on Wednesday that use of the vaccine cut the risk of getting dengue by 60.8 percent in the trial, which involved 20,875 children ages 9 to 16 from several countries in Latin America and the Caribbean.
Those who received the vaccine also had an 80.3 percent lower risk of being hospitalized for dengue compared with children who received injections of a placebo.
The results are roughly similar to those from the first large clinical trial, in which the vaccine reduced the incidence of dengue fever by 56.5 percent. That trial involved about 10,000 children in Southeast Asia.
“For the first time ever, after 20 years of research and industrial commitment, dengue is set to become a vaccine-preventable disease,” Olivier Charmeil, chief executive of Sanofi Pasteur, the vaccine division of Sanofi, said in a statement.
A question now is how widely such a vaccine would be adopted. Some experts hoped for a greater effectiveness, especially since in the first large trial, the vaccine was somewhat less effective in younger children, who are most vulnerable to the disease. Both trials were late-stage versions known as Phase 3.
“It’s certainly not anywhere close to what we had hoped, something that would reach up into the 90s,” said Dr. Scott B. Halstead, scientific adviser to the nonprofit Dengue Vaccine Initiative.
Still, he said, the vaccine does appear to prevent severe disease. Moreover, Sanofi is a few years ahead of others in developing a vaccine. Those factors could persuade countries to use the product.
Sanofi executives argue that with no other vaccine and no treatments available for dengue, a vaccine that reduces the number of cases by more than half and hospitalizations by 80 percent represents a big advance.
“When I talk to health ministers, they’re pretty excited about this, actually,” Christopher A. Viehbacher, Sanofi’s chief executive, told analysts in a conference call discussing quarterly earnings in late July.
Mr. Viehbacher said the company would apply for approvals in the first quarter of 2015 and hoped to begin sales in the fourth quarter of that year. He said the priority countries would be Mexico, Brazil and Colombia and possibly Singapore and Malaysia.
The company plans to apply eventually for approval in the United States as well, executives said.
Sanofi has invested more than 1.3 billion euros, or $1.7 billion, in developing the vaccine. Guillaume Leroy, dengue vaccine chief at Sanofi Pasteur, said the company had already begun manufacturing vaccine in a new factory it built outside Lyon so as to have enough ready by 2015. He said that beginning in 2016, the company would have the capacity to make 100 million doses a year.
An estimated 50 million to 100 million people a year are sickened by dengue, though that might be an underestimate. The disease, also known as breakbone fever, can cause high temperatures and intense joint and muscle pain.
In the most severe cases, infection causes hemorrhagic fever, which is characterized by bleeding and shock and can be fatal. The number of dengue cases has been increasing rapidly worldwide in part because of urbanization, since the mosquito that carries the disease is well adapted to urban areas. Dengue is even moving out of tropical areas in developing countries to industrialized countries in more temperate zones.
There is now an outbreak in Tokyo, the first one in Japan in nearly 70 years. Yoyogi Park is being fumigated to try to eliminate disease-carrying mosquitoes. The Florida Keys had its first cases in decades in 2009.
Sanofi said that in the second trial, as in the first, the vaccine was more effective in people previously exposed to dengue. That might make the vaccine especially useful in endemic areas, where people often are exposed more than once, but it would probably make it less useful for tourists traveling to an infected area.
The vaccine is a live weakened yellow fever virus that is genetically engineered to make proteins from the four subtypes of dengue virus. It is given as three shots spaced over a year.
The vaccine seems particularly weak against one of the four subtypes of dengue, known as Serotype 2. In the Latin America trial, the protection against that serotype was only 42.3 percent, compared with 50.3 percent protection against Serotype 1, and greater than 70 percent protection against Serotypes 3 and 4.
Sanofi said the vaccine seemed safe in the new trial, as it had in the previous trial, with the rate of so-called adverse events being the same in the vaccine arm and the control arm.
Sanofi announced the results in a news release, saying more detail would be presented at a medical conference in November and published in a journal. The trial took place in Brazil, Colombia, Honduras, Mexico and Puerto Rico.
http://www.nytimes.com/2014/09/04/business/experimental-vaccine-shows-promise-against-dengue-fever.html?
Dengue vaccine final trial results look promising
Bernama |Updated:September 04, 2014
The vaccine's final clinical trial, conducted on 20,875 children aged between 9 and 16 years in Latin America, recorded 60.8% overall efficacy against the disease.
KUALA LUMPUR: The outcome from the final study on dengue vaccine carried out by a renowned pharmaceutical conglomerate revealed that the vaccine recorded 60.8 percent overall efficacy against the disease.
The French drugmaker Sanofi's vaccine division, Sanofi Pasteur, had been carrying out research on the fastest-growing tropical disease over the past two decades.
Its final clinical trial was conducted on 20,875 children aged 9-16 years old across five countries in Latin America - Brazil, Columbia, Honduras, Mexico and Puerto Rico.
The results show the vaccine cuts the risk of hospitalisation by 80.3 percent after a three-dose vaccination schedule. It is also shown to be safe and provides high protection against dengue haemorrhagic fever.
The Latin American trial results indicated a 50.3 percent efficacy against serotype 1(ST1), 42.3 percent against ST2, 74 percent against ST3 and 77.7 percent against ST4.
One hospitalised every minute
Although the results show a weak rate against serotype 2, Sanofi was positive that the vaccine could be the best chance against the mosquito-borne disease.
The availability of the vaccine is in line with the World Health Organisation’s target of reducing morbidity by 25 percent and mortality by 50 percent by 2020, said Dr Muruga Vadivale, the Senior Medical Director of Dengue Medical Affairs for the Asia-Pacific Region of Sanofi Pasteur.
"We have to bear in mind that there is currently no treatment for dengue, and no vaccination or protection against the disease. Nearly half the world’s population are at risk. One person is hospitalised every single minute, every year.
"As a medical professional, I am very excited about the results. For the first time ever, after 20 years of research and development, dengue is set to become a vaccine preventable disease," the Singapore-based Dr Muruga toldBernamawhen contacted Wednesday.
Encouraged by results
On July 11, Sanofi announced in the reputable medical journalThe Lancet, that its dengue vaccine had passed phase III clinical trials in Southeast Asia, one of the last stages of tests for a drug before it can be put on the market.
The clinical trials carried out on 10,275 healthy children aged 2-14 years old in Malaysia, Indonesia, the Philippines, Thailand and Vietnam showed the vaccine reduced dengue by 56.5 percent in the vaccinated group compared with the control placebo group, as observed during 25 months of active surveillance.
The data also showed good serotype specific protection, with better protection shown against DEN3 and 4 (75 percent). However, as with the Latin American trials, the vaccine showed less protection against DEN1 (50 percent) and least to DEN2 (35 percent).
It is 88 percent effective against dengue haemmorhagic fever.
Malaysian virologist Emeritus Prof Datuk Lam Sai Kit viewed positively the consistent results of the clinical trials.
"Although the full details will not be available until the full publication is out, we can gauge that the vaccine has passed the safety test and that it offers protection against all four serotypes to varying degrees.
"Cutting down by half the number of people getting infected, reducing the hospitalisation rate by two-thirds and thus reducing cost, and preventing severe dengue by a similar amount (88 percent in Asia) are important findings.
"Personally, I think we have a powerful enough weapon to be seriously considered in the fight against dengue,” he said toBernamawhen contacted Wednesday.
The French drugmaker Sanofi's vaccine division, Sanofi Pasteur, had been carrying out research on the fastest-growing tropical disease over the past two decades.
Its final clinical trial was conducted on 20,875 children aged 9-16 years old across five countries in Latin America - Brazil, Columbia, Honduras, Mexico and Puerto Rico.
The results show the vaccine cuts the risk of hospitalisation by 80.3 percent after a three-dose vaccination schedule. It is also shown to be safe and provides high protection against dengue haemorrhagic fever.
The Latin American trial results indicated a 50.3 percent efficacy against serotype 1(ST1), 42.3 percent against ST2, 74 percent against ST3 and 77.7 percent against ST4.
One hospitalised every minute
Although the results show a weak rate against serotype 2, Sanofi was positive that the vaccine could be the best chance against the mosquito-borne disease.
The availability of the vaccine is in line with the World Health Organisation’s target of reducing morbidity by 25 percent and mortality by 50 percent by 2020, said Dr Muruga Vadivale, the Senior Medical Director of Dengue Medical Affairs for the Asia-Pacific Region of Sanofi Pasteur.
"We have to bear in mind that there is currently no treatment for dengue, and no vaccination or protection against the disease. Nearly half the world’s population are at risk. One person is hospitalised every single minute, every year.
"As a medical professional, I am very excited about the results. For the first time ever, after 20 years of research and development, dengue is set to become a vaccine preventable disease," the Singapore-based Dr Muruga toldBernamawhen contacted Wednesday.
Encouraged by results
On July 11, Sanofi announced in the reputable medical journalThe Lancet, that its dengue vaccine had passed phase III clinical trials in Southeast Asia, one of the last stages of tests for a drug before it can be put on the market.
The clinical trials carried out on 10,275 healthy children aged 2-14 years old in Malaysia, Indonesia, the Philippines, Thailand and Vietnam showed the vaccine reduced dengue by 56.5 percent in the vaccinated group compared with the control placebo group, as observed during 25 months of active surveillance.
The data also showed good serotype specific protection, with better protection shown against DEN3 and 4 (75 percent). However, as with the Latin American trials, the vaccine showed less protection against DEN1 (50 percent) and least to DEN2 (35 percent).
It is 88 percent effective against dengue haemmorhagic fever.
Malaysian virologist Emeritus Prof Datuk Lam Sai Kit viewed positively the consistent results of the clinical trials.
"Although the full details will not be available until the full publication is out, we can gauge that the vaccine has passed the safety test and that it offers protection against all four serotypes to varying degrees.
"Cutting down by half the number of people getting infected, reducing the hospitalisation rate by two-thirds and thus reducing cost, and preventing severe dengue by a similar amount (88 percent in Asia) are important findings.
"Personally, I think we have a powerful enough weapon to be seriously considered in the fight against dengue,” he said toBernamawhen contacted Wednesday.
Test vaccine for dengue seen as promising
11 JULY 2014 @ 8:11 AM
PARIS: A prototype vaccine for dengue that two years ago yielded lukewarm results has proved more effective after wider trials and is a potential arm against the disease, researchers said Friday.
Devised by the French pharmaceutical giant Sanofi Pasteur, the so-called CYD-TDV vaccine provided only 30 percent protection against the dangerous fever when first tested among children in Thailand.
Widened to trials in four other Asian countries, where disease conditions vary greatly, the vaccine’s protection has been shown to be significantly higher, at 56.5 percent overall, the scientists said.
The result falls short of the benchmark set by classic vaccines such as those for polio and measles, which can be more than 99 percent effective.
One reason for this is that CYD-TDV performed poorly against one of the four strains of dengue virus, the investigators reported in The Lancet.
These strains, or serotypes, circulate simultaneously, which means a vaccine should ideally protect against all of them.
Even so, the prototype was safe and well tolerated and its shield, if only partial, means it should be enlisted in the fight against dengue, they argued.
“Our results suggest that vaccination with CYD-TDV can reduce the incidence of symptomatic dengue infection by more than half and importantly reduced severe disease and hospitalisations,” said Maria Rosario Capeding from the Philippines’ Research Institute for Tropical Medicine.
“This candidate vaccine has the potential to have a significant impact on public health in view of the high disease burden in endemic countries.”
Dengue is a potentially fatal fever, caused by a virus transmitted by a mosquito when it takes its blood meal, and is especially dangerous for children.
The virus infects around 390 million people each year, of whom about 96 million fall sick, according to UN estimates.
It was once considered a disease of the tropics that was endemic in only nine countries.
But globalisation, climate change and jet travel are helping it to move into more temperate zones.
According to the World Health Organization (WHO) cases of dengue have risen 30 fold over the last 50 years, and more than half of the world’s population are at risk of the disease.
The CYD-TDV vaccine was tested as a so-called Phase IIb trial among just over 4,000 children in rural Thailand, the results of which were reported in September 2012.
The new figures are those of a Phase III trial – normally the final step in the process to test new drugs for safety and efficiency – carried out in Indonesia, Malaysia, the Philippines and Vietnam, as well as in Thailand.
More than 10,000 children aged two to 14 years were enrolled. They were randomly assigned to receive three injections of the vaccine or a placebo over 12 months, and were followed for up to two years.
During this period a total of 150 dengue cases occurred, a majority of them in the placebo group, demonstrating an overall effectiveness of 56.5 percent.
But the protection varied according to the serotype – more than 75 percent against virus types 3 and 4; 50 percent against type 1; but only 35 percent against type 2.
On the plus side, those who had received the vaccine were also far less likely to fall ill with a severe form of the disease, dengue haemorrhagic fever, which leads to half a million hospitalisations each year.
In a commentary, Annelies Wilder-Smith, a professor at Singapore’s Nanyang Technological University, said a vaccine that halved annual cases of dengue “would present a significant public health benefit” but was not a magic bullet.
“For the moment, the CYD-TDV vaccine is the best we have; however, with 56 percent efficacy it will never be a single solution,” Wilder-Smith said.
Other strategies, including better approaches to tackling mosquitoes that cause the problem, would also have to be part of the campaign, she said.
The children in the trial are being followed up for another four years to see whether the vaccine’s promise still holds up. -AFP
