− In long-term exploratory analysis, TAK-003 prevented 84% of hospitalisations and 61% of symptomatic dengue illness overall, with no identified important safety risks.
− Results through 4.5 years conclude the evaluation of the primary two-dose series of TAK-003.
− TAK-003 is currently undergoing regulatory review for potential licensure in both the European Union and selected dengue-endemic countries.
SINGAPORE, June 9, 2022– Takeda Pharmaceutical Company Limited (“Takeda”) today announced that its dengue vaccine candidate, TAK-003, prevented 61% of symptomatic dengue cases and 84% of hospitalised cases with no important safety risks identified in the overall population. This includes both seropositive and seronegative individuals through four and a half years (54 months) after vaccination in the pivotal Phase 3 Tetravalent Immunization against Dengue Efficacy Study (TIDES) trial. These data were presented on June 9, 2022, at the 8th Northern European Conference on Travel Medicine (NECTM8), with plans to feature the results at the 5th Asia Dengue Summit on June 14, 2022.
“The burden of dengue is far reaching and over half of the world’s population is at risk of dengue each year,” said Ooi Eng Eong, PhD, MD, Duke-NUS Medical School, Singapore. “There is an urgent need for impactful prevention tools to combat the disease. The long-term TIDES results indicate that TAK-003 could be an important addition to the tools we have to prevent dengue, particularly given the demonstrated protection against hospitalisations.”
“Home to 70% of global dengue incidence, Asia Pacific is highly susceptible to the threat of dengue. Indonesia and Thailand are among the most highly endemic countries in the world,” said Professor Duane Gubler, Emeritus Professor and Founding Director of the Emerging Infectious Diseases (EID) Signature Research Programme at Duke-NUS Medical School. “The positive 54-month TAK-003 data signifies that a new era of dengue management might be within our reach, mitigating the impacts of dengue and reducing hospitalisation rates for individuals regardless of previous dengue infections. It is important to note, however, that to achieve optimal results with the vaccine, it should be integrated with existing Aedes Aegypti mosquito control efforts.”
Singapore has witnessed a high number of dengue cases over the past few months, even before the traditional peak dengue season from June to October. As of end-May, there are 398 active dengue clusters, with 103 clusters containing 10 or more cases. Compared to the same period last year (April 2022 vs April 2021), the population of Aedes aegypti mosquitoes is 22% higher, exacerbating the dengue situation in the nation while putting pressure on healthcare systems.
Through four and a half years, TAK-003 demonstrated overall vaccine efficacy (VE) of 61.2% (95% CI: 56.0, 65.8) against virologically-confirmed dengue (VCD), with 64.2% VE (58.4, 69.2) in seropositive individuals and 53.5% VE (41.6, 62.9) in seronegative individuals. TAK-003 also demonstrated 84.1% VE (95% CI: 77.8, 88.6) against hospitalised dengue, with 85.9% VE (78.7, 90.7) in seropositive individuals and 79.3% VE (63.5, 88.2) in seronegative individuals. Observations of VE varied by serotype and remained consistent with previously reported results. TAK-003 was generally well tolerated and there were no important safety risks identified. No evidence of disease enhancement was observed over the 54-month follow-up exploratory analysis, either.
“Dengue is estimated to cost the region an annual economic burden of US$950 million(2) and a global burden of almost US$9 billion, with 40% being from decreased productivity3. Furthermore, dengue outbreaks pose challenges to healthcare systems and resources,” said Thomas Willemsen, Senior Vice President of Takeda Pharmaceuticals (Asia Pacific) Pte. Ltd. “Takeda’s investments in vaccines support our ambitions to bring TAK-003 to people who can potentially benefit from it. The TIDES trial was designed to account for both dengue-naïve and dengue-exposed populations in Asia and Latin America where outbreaks are prevalent, and we are proud that the results continue to demonstrate the safety and efficacy of the vaccine and its ability to provide long-term protection against dengue,” he continued.
“Singapore continues to place effective dengue management at the forefront of its efforts with multiple vector control strategies in place, such as the use of Wolbachia mosquitoes and regular fumigation of public areas. Prioritisation of personal responsibility has also played a role in ensuring home environments are free from Aedes Aegypti mosquitoes,” said Dr Ellyana Ismail, Head of Medical Affairs, Malaysia and Singapore, Takeda. “With the demonstrated efficacy and safety of the TAK-003 dengue vaccine candidate, we are excited to support ongoing efforts and provide those living in Singapore and the broader ASEAN region with an integrated solution to manage dengue following its approval.”
These new long-term results supplement previously published TIDES data that demonstrated the candidate vaccine met its primary endpoint of overall VE against VCD, with 80.2% efficacy at 12-months follow-up, as well as all secondary endpoints for which there were a sufficient number of dengue cases at 18-months follow-up, including 90.4% VE against hospitalised dengue. While the long-term follow-up for the primary two-dose series has been completed, the TIDES trial remains ongoing to evaluate the safety and efficacy of a booster dose. The TIDES trial is Takeda’s largest interventional clinical trial to date, enrolling more than 20,000 healthy children and adolescents four to 16 years of age, across eight dengue-endemic countries, over the past four and a half years.
TAK-003 is currently undergoing regulatory review for the prevention of dengue disease in children and adults in the European Union and selected dengue-endemic countries.
Takeda's tetravalent dengue vaccine candidate (TAK-003) is based on a live-attenuated dengue serotype 2 virus, which provides the genetic “backbone” for all four vaccine viruses.4 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.5 The pivotal Phase 3 Tetravalent Immunisation against Dengue Efficacy Study (TIDES) trial met its primary endpoint of overall vaccine efficacy (VE) against virologically-confirmed dengue (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 hospitalised dengue and VE in baseline seropositive and baseline seronegative individuals.6,7 Efficacy varied by serotype. The results demonstrated TAK-003 was generally well tolerated, and there have been no important safety risks observed to date.
About the Phase 3 TIDES (DEN-301) Trial
The double-blind, randomised, placebo-controlled Phase 3 Tetravalent Immunisation against Dengue Efficacy Study (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.6 Study participants were randomised 2:1 to receive two doses of TAK-003 0.5 mL or placebo on Months 0 and 3, administered subcutaneously.6 The study is comprised of five parts. Part 1 and the primary endpoint analysis evaluated vaccine efficacy (VE) and safety through 12 months after the second dose.6 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 hospitalised dengue.6 Part 3 is evaluating VE and long-term safety by following participants for an additional two and a half to three years, as per World Health Organization (WHO) recommendations.8 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 4.8
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.8 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.
Dengue is the fastest spreading mosquito-borne viral disease and was one of the WHO’s top 10 threats to global health in 2019.9,10 Dengue is mainly spread by Aedes aegypti mosquitoes and, to a lesser extent, Aedes albopictus mosquitoes. It is caused by any of four dengue virus serotypes, each of which can cause dengue fever or severe dengue. The prevalence of individual serotypes varies across different geographies, countries, regions, seasons and over time.11 Recovery from infection by one serotype provides lifelong immunity against only that serotype, and later exposure to any of the remaining serotypes might be associated with an increased risk of severe disease.
Dengue is pandemic prone, and outbreaks are observed in tropical and sub-tropical areas and have recently caused outbreaks in parts of the continental United States and Europe.12,13 Approximately half of the world now lives under the threat of dengue, which is estimated to cause 390 million infections, 500,000 hospitalisations and 20,000 deaths globally each year.12,14 The dengue virus can infect people of all ages and is a leading cause of serious illness among children in some countries in Latin America and Asia.12
Takeda’s Commitment to Vaccines
Vaccines prevent 3.5 to 5 million deaths each year and have transformed global public health.15 For more than 70 years, Takeda has supplied vaccines to protect the health of people in Japan. Today, Takeda’s global vaccine business is applying innovation to tackle some of the world’s most challenging infectious diseases, such as dengue, COVID-19, pandemic influenza and Zika. Takeda’s team brings an outstanding track record and a wealth of knowledge in vaccine development and manufacturing to advance a pipeline of vaccines to address some of the world’s most pressing public health needs. For more information, visit www.TakedaVaccines.com.
Takeda is a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to discover and deliver life-transforming treatments, guided by our commitment to patients, our people and the planet. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Rare Genetics and Hematology, Neuroscience, and Gastroenterology (GI). We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people’s lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R&D engine and capabilities to create a robust, modality-diverse pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries and regions. For more information, visit https://www.takeda.com.
Takeda Pharmaceuticals (Asia Pacific) Pte. Ltd.
Bethany Chuah – APAC Communications Lead
Hui Ling Chee – Communications Manager for Vietnam, Malaysia, Philippines, Singapore (VMAPS) Cluster
Speyside Group Pte. Ltd. (Public Relations Consultancy)
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This press release contains information about products that may not be available in all countries, including Singapore, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Intended as scientific information sharing in trade or professional publications, nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development.
- BMC Public Health. Estimating dengue incidence and hospitalization in Malaysia, 2001 to 2013. BMC Public Health 18, Article number: 946 (2018). Retrieved March 2022.
- PLOS. Neglected Tropical Disease. Economic and Disease Burden of Dengue in Southeast Asia. February 2013.
- BMC Infectious Diseases. Productivity costs from a dengue episode in Asia: a systematic literature review. BMC Infectious Diseases 20, Article number : 393 (2020).
- Huang CY-H, et al. Genetic and phenotypic characterization of manufacturing seeds for tetravalent dengue vaccine (DENVax). PLoS Negl Trop Dis. 2013;7:e2243.
- Tricou, V, Sáez-Llorens X, et al. Safety and immunogenicity of a tetravalent dengue vaccine in children aged 2-17 years: a randomised, placebo-controlled, phase 2 trial. Lancet. 2020. doi:10.1016/S0140-6736(20)30556-0.
- Biswal S, et al. Efficacy of a tetravalent dengue vaccine in healthy children and adolescents. N Engl J Med. 2019; 2019;381:2009-2019.
- Biswal S, et al. Efficacy of a tetravalent dengue vaccine in healthy children aged 4-16 years: a randomized, placebo controlled, phase 3 trial. Lancet. 2020. 2020;395:1423-1433.
- ClinicalTrials.Gov. Efficacy, Safety and Immunogenicity of Takeda's Tetravalent Dengue Vaccine (TDV) in Healthy Children (TIDES). Retrieved March 2021.
- World Health Organization. Factsheet. Dengue and Severe Dengue. April 2019. Retrieved February 2021.
- World Health Organization. Ten threats to global health in 2019. 2019. Retrieved February 2021.
- Guzman MG, et al. Dengue: a continuing global threat. Nature Reviews Microbiology. 2010;8:S7-S16.
- Knowlton K, et al. Mosquito-Borne Dengue Fever Threat Spreading in the Americas. The Natural Resources Defense Council (NRDC). 2009. Retrieved February 2021.
- Chan E, et al. Using web search query data to monitor dengue epidemics: a new model for neglected tropical disease surveillance. PLoS Negl Trop Dis. 2011;5:e1206.
- Centers for Disease Control and Prevention. About Dengue: What You Need to Know. May 2019. Retrieved February 2021.
- World Health Organization. Vaccines and immunization. 2022. Retrieved May 2022.