Dengue virus. All images courtesy of Sanofi Pasteur.

Are we one step closer to a dengue vaccine?

In September 2014, pharmaceutical firm Sanofi Pasteur announced the results of the second wave of its Phase III clinical trials. The news builds on the positive results of the first half of its Phase III clinical trials in Asia. In the first trial involving 10,275 children aged 2-14 years across Malaysia, the Philippines, Thailand, and Vietnam, Sanofi Pasteur reported that the vaccine candidate was 57% effective against symptomatic dengue.

More importantly, the trial found the vaccine candidate to be 89% effective against severe dengue and reduced hospitalizations by 67%.

The second trial involved a three-dose vaccination schedule in 20,875 children aged 9-16 years across Brazil, Colombia, Mexico, Honduras, and Puerto Rico. Sanofi Pasteur reported that the vaccine candidate showed overall efficacy of 60.8% against symptomatic dengue, and reduced hospitalizations by 80.3%.

According to the pharmaceutical firm, in both trials the level of efficacy varied between each dengue serotype: ranging from 50% for type one, 35% for type two, 78% for type three, and 75% for type four in the Asian trial.

The results were consistent, with a little less variation, in the Latin American trial: 50% for type one, 42% for type two, 74% for type three, and 77% for type four. These results indicate that the vaccine could bring a good contribution in reaching the World Health Organization (WHO) objectives for the Global strategy for dengue prevention and control, 2012–2020, which aims to reduce dengue mortality by 50% and morbidity by at least 25% by 2020.

Reducing the severity of dengue

“Dengue is so unpredictable and you really don’t know if a patient with dengue will go into shock or just have a mild case,” reveals Dr. Rosario Capeding, head of the dengue vaccine group at the Research Institute for Tropical Medicine in the Philippines.

“The vaccine will have a major impact because the efficiency is good enough. But the most important finding was that the vaccine candidate reduced the severity of the disease. As a mother and a clinician, that is what we are looking for.

If you have a child with dengue, it gives you more confidence that their dengue will just be mild.” “It took 20 years for Sanofi Pasteur to develop the vaccine because it’s different,” notes Dr. Capeding.

“It protects the individual against all four serotypes, any or all of which may be circulating in a region at any time. In the early years, the 1940s, dengue vaccine only protected against one serotype.” “The development was complicated further because, unlike other vaccines, you can’t test it on animals,” she continues. “Monkeys can get the disease, but its manifestation in monkeys is different to humans.”

Impact where it is needed the most

Confirming the positive results from Asia, the results from Latin America are welcome news at Sanofi Pasteur. “We’re really pleased with the results with the second trial as they show consistent results across the two phase III studies,” says Melanie Saville, chief medical and clinical officer (CMCO), Dengue at Sanofi Pasteur.

“We are continuing to complete the analysis and share that with experts in the field and with the regulators, with a view to submitting for approval in some key countries in endemic areas.”

Melanie hopes a vaccine could be available in some key endemic countries in the second half of 2015. “With 100 countries at risk, there is an unmet medical need with no vaccine and no treatment at the moment. This is very important for the fight against dengue.” Dr. Capeding anticipates that she, like other experts on the dengue vaccine around the world, will be invited to participate in discussions around priorities for the vaccine in her local region – the Philippines – and possibly around integrating the vaccine into the national immunization program.

This isn’t the only dengue vaccine in development. Other firms working on a dengue vaccine include Takeda, GlaxoSmithKline, and Merck (all in collaboration with other organizations). None of these are at Phase III of clinical trials, but we’ll be creating a separate post about what they are working on soon.