Takeda Initiates Global Phase 3 Clinical Trial (TIDES) of Dengue Vaccine Candidate (TAK-003)

- Study to evaluate vaccine protection against all four strains of dengue virus, regardless of previous exposure

Osaka, Japan, September 7, 2016 – Takeda Pharmaceutical Company Limited [TSE: 4502], (“Takeda”) today announced that it has vaccinated the first subject in the Tetravalent Immunization against Dengue Efficacy Study (TIDES), a Phase 3 double-blind, randomized and placebo-controlled trial of its live-attenuated tetravalent dengue vaccine candidate (TAK-003).

TIDES will enroll approximately 20,000 healthy children between the ages of four and 16 years living in dengue-endemic countries in Latin America and Asia. The study willevaluate the efficacy of the vaccine candidate to protect subjects against symptomatic dengue fever caused by any of the four dengue virus serotypes, regardless of age and whether the individual has previously been exposed to the virus. The study will also evaluate vaccine safety and immunogenicity, and will involve two doses of the vaccine candidate or placebo administered 90 days apart.¹

According to the World Health Organization (WHO), dengue is the fastest spreading mosquito-borne viral disease.² Forty percent of the world’s population lives under the threat of the dengue virus, which causes 390 million infections and more than 20,000 deaths each year around the world in people of all ages.^{3, 4}

“The initiation of Phase 3 trials for our dengue vaccine candidate is a critical milestone, bringing us closer to delivering a vaccine that can address important unmet needs in dengue prevention. This is a significant achievement for Takeda’s vaccine program and underscores our ongoing commitment to addressing critical global health threats,”said Rajeev Venkayya, MD, President of the Global Vaccine Business Unit at Takeda. “The progress of our dengue program, along with other recent achievements, such as Phase 2b field trial initiation for our norovirus vaccine candidate and our partnership with the Bill & Melinda Gates Foundation to develop a Sabin-strain inactivated poliovirus vaccine (sIPV) exemplify how we are researching, developing and providing vaccines to protect populations in need, wherever they may reside.”

While vector-control efforts are important, effective dengue disease prevention will also require vaccination. An ideal vaccine would have an acceptable safety profile and protect against all four types of the virus in both adults and children, whether or not they have been previously infected with dengue,” said Duane Gubler, Professor Emeritus and Founding Director, Signature Research Program in Emerging Infectious Disease, Duke-NUS Medical School.

TIDES will build on previous studies which have assessed the tolerability, safety and immunogenicity of the vaccine against all four dengue serotypes in multiple age groups to determine whether the vaccine helps prevent symptomatic dengue.^{5, 6, 7} In Phase 1 and Phase 2 studies, Takeda’s vaccine candidate induced neutralizing antibody responses against all four dengue virus serotypes across age groups and in both seropositive and seronegative individuals with no observed safety concerns.^{5, 6, 7} Interim results of one Phase 2 study (DEN-203) showed the vaccine to be generally safe and well tolerated.⁶ Results also showed that adults vaccinated with two doses had a sustained immune response against all four serotypes of the dengue virus, even after two years^.6 Interim results of another Phase 2 study (DEN-204) showed an acceptable safety profile in endemic pediatric populations, as well as antibody responses against the four dengue serotypes in dengue seropositive and seronegative participants, with a sustained immune response through 180 days.⁷

About the Dengue Vaccine Candidate (TAK-003)

Takeda’s tetravalent dengue vaccine candidate (TAK-003) is based on a live-attenuated dengue serotype 2 virus (DENV-2), which provides the genetic ‘backbone’ for all four vaccine viruses.⁸ Takeda’s dengue vaccine is being developed to support the protection of populations and individuals at risk for dengue across geographies whether or not they have had previous exposure to dengue virus, including: children and adults, travelers and those living in endemic areas

Phase 1 data has been published in the Journal of Infectious Diseases, Lancet Infectious Diseases, and Vaccine.  Interim results of DEN-203, a Phase 2, placebo-controlled, multi-center, age-descending trial, were presented during the American Society of Tropical Medicine and Hygiene (ASTMH) meeting in October 2015.6Interim results of DEN-204, a Phase 2, placebo-controlled, multi-center trial were presented during the 5th Annual Pan-American Dengue Research Network Meeting in May 2016.⁷

Takeda’s Commitment to Vaccines

Vaccines prevent more than two million deaths each year and have transformed global public health.⁹ For 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, norovirus and polio. Our team brings an outstanding track record and a wealth of knowledge in vaccine development, manufacturing and global access to advance a pipeline of vaccines to address some of the world’s most pressing public health needs.

About Takeda

Pharmaceutical Company Limited Takeda Pharmaceutical Company Limited (TSE: 4502) is a global, R&D-driven pharmaceutical company committed to bringing better health and a brighter future to patients by translating science into life-changing medicines. Takeda focuses its research efforts on oncology, gastroenterology and central nervous system therapeutic areas. It also has specific development programs in specialty cardiovascular diseases as well as late-stage candidates for vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. New innovative products, especially in oncology and gastroenterology, as well as its presence in emerging markets, fuel the growth of Takeda. More than 30,000 Takeda employees are committed to improving quality of life for patients, working with our partners in health care in more than 70 countries. For more information, visit http://www.takeda.com/news.

 

Contact:

For media outside of Japan:
Elissa Johnsen
TEL: +1 224-554-3185
[email protected]

For Japanese
Tsuyoshi Tada
TEL:+81-3-3278-2417
[email protected]

¹ Efficacy, Safety and Immunogenicity of Takeda's Tetravalent Dengue Vaccine (TDV) in Healthy Children (TIDES) (2016). ClinicalTrials.gov. Accessed may 2016, from https://clinicaltrials.gov/ct2/show/NCT02747927?term=den-301&rank=1

² World Health Organization (2015). Vector-borne diseases: Dengue. Accessed September 2016, from http://www.who.int/mediacentre/factsheets/fs387/en/index2.html

³ World Health Organization (2015). Dengue and severe dengue. Accessed May 2016, from

http://www.who.int/mediacentre/factsheets/fs117/en/

⁴ Centers for Disease Control and Prevention (2015). Dengue homepage: Epidemiology. Accessed September 2016, from http://www.cdc.gov/dengue/epidemiology/

⁵ Osorio JE, Velez ID, Thomson C, et al. Safety and immunogenicity of a recombinant live attenuated tetravalent dengue vaccine (DENVax) in flavivirus-naive healthy adults in Colombia: a randomised, placebo-controlled, phase 1 study. The Lancet Infectious diseases 2014;14(9):830-8.

⁶ Wallace, D. (2015). Persistence of neutralizing antibodies one year after two doses of a candidate recombinant tetravalent dengue vaccine in subjects aged from 1.5 to 45 years. Presented at 6th Annual Meeting, American Society of Tropical Medicine and Hygiene.

⁷ Saez-Llorens X., et al. (2016). Phase II, double-blind, controlled trial to assess the safety and immunogenicity of different schedules of Takeda’s Tetravalent Dengue Vaccine Candidate (TDV) in healthy subjects aged between 2 and <18 years and living in dengue endemic countries in Asia and Latin America. Presented at 5th Pan-American Dengue Research Network Meeting.

⁸ Huang, C. Y.-H., Osorio, J.E., et. al: Genetic and Phenotypic Characterization of Manufacturing Seeds for Tetravalent Dengue Vaccine (DENVax)

⁹ UNICEF Immunization Facts and Figures April 2013. Accessed September 2015, from http://www.unicef.org/immunization/files/UNICEF_Key_facts_and_figures_on_Immunization_April_2013(1).pdf