The World Health Organization (WHO) said that in recent decades, the global rate of incidence of dengue, the mosquito-caused viral disease, has grown exponentially, with an estimated 100-400 million infections each year.
This is why pharmaceutical companies are scrambling hard to come up with a vaccine to combat dengue and prevent more infections that may lead to more deaths.
Takeda Pharmaceutical Company, Limited is one of those companies. In a statement sent to FrontpagePH.com, Takeda announced that its dengue vaccine candidate called “TAK-003,” demonstrated continued protection against dengue illness and hospitalization, regardless of an individual’s previous dengue exposure, with no important safety risks identified through three years after vaccination in the ongoing pivotal Phase 3 Tetravalent Immunization against Dengue Efficacy Study or TIDES trial. TIDES enrolled more than 20,000 healthy children and adolescents ages four to 16 years in dengue-endemic countries in Latin America and Asia.
“Dengue epidemics occur suddenly, and hospitals can become overwhelmed with severe disease cases and people seeking testing,” said LakKumar Fernandoi, M.D., Center for Clinical Management of Dengue and Dengue Haemorrhagic Fever, Negombo General Hospital, Sri Lanka and a primary investigator of the TIDES trial.
“Results from the long-term analysis of Takeda’s dengue vaccine candidate suggest that it could help with outbreak prevention, reduce rates of hospitalization and protect people from dengue regardless of their previous exposure. Importantly, no important safety risks were identified.”
Safety and efficacy results from the 36-month follow-up exploratory analysis of TIDES were presented on May 22, 2021, at the 17th Conference of the International Society of Travel Medicine (CISTM). Through three years after the second dose, TAK-003 demonstrated overall vaccine efficacy (VE) of 62.0 percent against virologically-confirmed dengue (VCD), with 65 percent VE in seropositive individuals and 54.3 percent VE in seronegative individuals. TAK-003 also demonstrated 83.6 percent VE against hospitalized dengue, with 86 percent VE in seropositive individuals and 77.1 percent VE in seronegative individuals.
Observations of varied VE by serotype remained consistent with previously reported results and no evidence of disease enhancement was observed. TAK-003 was generally well tolerated, and there were no important safety risks observed. The results reinforce the potential of TAK-003 to help protect those who are living in or traveling to dengue-endemic countries.
“Our dengue vaccine candidate continued to provide protection against dengue throughout three years, and was especially robust in preventing hospitalization,” said Derek Wallace, VP, Dengue Global Program Leader at Takeda. “These results reinforce my confidence that TAK-003 can help address the significant global burden of dengue.”
The TIDES trial has been amended to include the evaluation of a booster dose to address the waning of overall VE observed over time (from 12 through 36 months after the second dose), largely driven by outpatient dengue. Takeda intends to publish the results of the 36-month exploratory analysis in a peer-reviewed journal this year.
TIDES safety and efficacy data through 36-months follow-up was included in regulatory submissions to the European Union and dengue-endemic countries and will be part of additional filings planned for 2021, including in the United States. Takeda will seek an indication for TAK-003 for the prevention of dengue disease in individuals four to 60 years of age, regardless of previous virus exposure, based on data in both adults and children. There remains a need for dengue vaccines that can be used in both dengue-naïve and dengue-exposed adults and children.
Takeda’s TAK-003 is based on a live-attenuated dengue serotype 2 virus, which provides the genetic “backbone” for all four vaccine viruses. Clinical Phase 2 data in children and adolescents showed that TAK-003 induced immune responses against all four dengue serotypes, in both seropositive and seronegative participants, which persisted through 48 months after vaccination, and the vaccine was found to be generally safe and well tolerated.
The pivotal Phase 3 TIDES trial met its primary endpoint of overall VE against VCD at 12-months follow-up and all secondary endpoints at 18-months follow-up, for which there were a sufficient number of dengue cases, including VE against hospitalized dengue and VE in baseline seropositive and baseline seronegative individuals. Efficacy varied by serotype. The results demonstrated TAK-003 was generally well tolerated, and there have been no important safety risks observed to date.
The double-blind, randomized, placebo-controlled Phase 3 TIDES trial is evaluating the safety and efficacy of two doses of TAK-003 in the prevention of laboratory-confirmed symptomatic dengue fever of any severity and due to any of the four dengue virus serotypes in children and adolescents. The TIDES trial is Takeda’s largest interventional clinical trial to date and enrolled over 20,000 healthy children and adolescents ages four to 16 years living in dengue-endemic areas.
Study participants were randomly assigned to receive either TAK-003 0.5 mL or placebo by subcutaneous injection on Day 1 and Day 90. The study is comprised of five parts. Part 1 and the primary endpoint analysis evaluated VE and safety through 12 months after the second dose. Part 2 continued for an additional six months to complete the assessment of the secondary endpoints of VE by serotype, baseline serostatus and disease severity, including VE against hospitalized dengue.
Part 3 is evaluating VE and long-term safety by following participants for an additional two and a half to three years, while Part 4 will evaluate efficacy and safety for 13 months following booster vaccination and Part 5 will evaluate long-term efficacy and safety for one year after completion of Part 4.
The trial is taking place at sites in dengue-endemic areas in Latin America (Brazil, Colombia, Panama, the Dominican Republic and Nicaragua) and Asia (Philippines, Thailand and Sri Lanka) where there are unmet needs in dengue prevention and where severe dengue is a leading cause of serious illness and death among children. Baseline blood samples were collected from all individuals participating in the trial to allow for evaluation of safety and efficacy based on serostatus. Takeda and an independent Data Monitoring Committee of experts are actively monitoring safety on an ongoing basis.