New dengue vaccine performs well in large trials

Publicação: 9 de December de 2019

Manufactured by pharmaceutical Takeda, overall, the drug was 80.2% effective

The experimental vaccine was tested on 20 thousand children in Asia and Latin America. The company’s next steps are to seek regulatory approval in affected countries, including Brazil

An experimental dengue vaccine called TAK-003, showed promising initial results in a large study in several countries. Manufactured by the Takeda Pharmaceutical Company, the drug was 80.2% effective at preventing the disease, according to a new study published by The New England Journal of Medicine entitled “Efficacy of a Tetravalent Dengue Vaccine in Healthy Children and Adolescents. However, questions about its effectiveness and safety remain the main concern. It is unclear, for example, whether the vaccine may increase the severity of the disease in some recipients, as with Sanofi’s Dengvaxia, which was administered to a million children in the Philippines.

But it seems that the new Takeda vaccine seems to work in those who have never been exposed to dengue viruses. Based on a weakened strain of the dengue virus, so far, the tests have been carried out on 20 thousand children and adolescents aging from 4 to 16 years-old in eight countries in Asia and Latin America, where the disease is endemic. Twelve months after participants received their second and last dose, the researchers compared how many people in the placebo and vaccine groups developed confirmed cases of infection with any of the four different strains, or serotypes of the dengue virus. The vaccine was 97.7% effective against dengue serotype 2. For serotype 1, the number of infections decreased by 73.7%. While for serotype 3, by 62.3%. Among participants who fell ill, the risk of hospitalization reduced by 95.4%.

According to Dr. Shibadas Biswal, Takeda’s medical director, analyzing the data at the end of the first part of the study shows that the vaccine was generally well tolerated and that no major safety risks have been observed so far. “We will continue to evaluate safety and effectiveness for a period of four and a half years. In addition, we are motivated to see similar efficacy rates in participants – 80.2% in the 12 months after the second dose – regardless of previous dengue exposure”, he said.

Regarding the risk of the vaccine potentiating recurrence cases, Dr. Biswal explains that based on the analysis at the end of the first Tetravalent Immunization Against Dengue Efficacy Study (TIDES), there is no evidence of disease enhancement among the initial seronegative population that received the vaccine. According to the doctor, this population will be closely monitored as new data become available from the other two parts of the test.

Takeda’s proposed vaccine is designed to protect against all four dengue serotypes and activate various branches of the immune system, including antibodies and immune cells. “TAK-003 is based on live attenuated dengue serotype 2 virus (DENV-2), which provides the genetic ‘skeleton’ for all four vaccine serotypes. “Because our proposed vaccine is based on an attenuated form of the dengue virus itself, it exposes the individual to various components of the virus that may be important in protecting against future virus infections”, he said.

Unlike Dengvaxia efficacy tests, Takeda evaluated pre-vaccination and whether study participants had antibodies from a previous dengue infection. About one in four participants was seronegative, and while no obvious signs of vaccine-induced damage occurred, the article demonstrates that overall vaccine efficacy in this group fell to 74.9%. In addition, the vaccine did not protect these people against dengue serotype 3 – the results were inconclusive.

Although we cannot make comparisons between our proposed vaccine and others, we are happy to share specific information about TAK-003. Our phase 3 TIDES was designed differently from other studies. We designed it to assess safety and efficacy against all four serotypes and regardless of previous dengue exposure. Baseline blood samples were collected from all subjects participating in the study to allow the evaluation of safety and efficacy based on serological status”, said Dr. Biswal.

The TIDES is a phase 3 randomized, placebo-controlled, double-blind study designed to evaluate the efficacy, safety and immunogenicity of two doses of the tetravalent dengue candidate vaccine in unblinded and exposed individuals. This is Takeda’s largest interventional clinical trial to date, with more than 20 thousand healthy children and adolescents aging from four to 16 years-old living in endemic areas.

The next steps are to try regulatory approval in affected countries, including Brazil. The first request should be submitted in the second half of 2020. Dengue is currently one of the major reemerging diseases and has become a global problem making no tropical or subtropical country successful in its control. In 2019, it was considered one of the top 10 global health threats by the World Health Organization (WHO). Each year, about 400 million people are infected and about 25 thousand deaths are recorded.

Asked about the prospect of commercializing of the vaccine, Dr. Biswal is emphatic to say that it is too early to comment on specific details of access, but it will be focused on providing to endemic countries and where there is a greater need, alongside supplying in non-endemic countries. “We want to get the vaccine to people who need it as soon as possible. The planned dossier will include safety and efficacy data from the main TIDES and supporting data from other Phase 3 studies conducted by the Japanese pharmaceutical. In addition to the overall vaccine efficacy of 80.2% seen in the primary endpoint analysis, the doctor also says they are encouraged by the 95.4% reduction in the studied hospitalizations related to dengue.