TAK-003 Dengue Vaccine Description

Takeda's TAK-003 is an investigational live-attenuated tetravalent dengue vaccine, preventing dengue fever caused by any of the four serotypes of the dengue virus of which can cause dengue fever or Severe Dengue.

TAK-003 (TDV) is based on a live-attenuated dengue serotype 2 virus, which provides the genetic “backbone” for all 4 dengue serotypes.

Takeda's current clinical development program consists of five Phase 3 trials. Clinical Phase 1 and 2 data in children and adolescents showed that TAK-003 induced immune responses against all four dengue serotypes in seropositive and seronegative participants. The vaccine was found to be generally safe and well-tolerated.

In a November 2019 study, Takeda’s dengue vaccine candidate demonstrated protection against virologically-confirmed dengue, the trial primary endpoint, in children ages 4 to 16 years. The vaccine efficacy (VE) was 80.2% in the 12-month period after the 2nd vaccine dose, which was administered 3-months after the 1st dose.

The Lancet published an article on March 17, 2020, Safety and immunogenicity of a tetravalent dengue vaccine in children aged 2–17 years: a randomized, placebo-controlled, phase 2 trial, which concluded saying 'TAK-003 elicited antibody responses against all four serotypes, which persisted to 48 months post-vaccination, regardless of baseline serostatus.'

And recently, on July 13, 2020, the Long-term safety and immunogenicity of a tetravalent dengue vaccine candidate in children and adults: a randomized, placebo-controlled, phase 2 study, found at Month 36, seropositivity rates were 97.3%, 98.7%, 88.0% and 56.0% for DENV-1, -2, -3 and -4, respectively. Seropositivity rates varied significantly for DENV-4 according to serostatus at baseline (89.5% in seropositive versus 21.6% in seronegative). No vaccine-related SAEs were reported.

The TAK-003 vaccine is not currently licensed anywhere in the world. 

For more information, visit www.TakedaVaccines.com.

TAK-003 Denge Vaccine Indication

TAK-003 is indicated for the prevention of the Dengue virus caused by any of the 4 Dengue serotypes. Dengue is the fastest spreading mosquito-borne viral disease and is one of the World Health Organization’s top 10 global health threats in 2019.

TAK-003 is the second dengue vaccine to enter clinical trials, after Sanofi Pasteur's Dengvaxia. Sanofi's vaccine was 56% to 61% effective in preventing dengue in children, but it was tied to severe illness in dengue-naive children who received the vaccine and then contracted the virus.

Takeda’s TAK-003 is based on a dengue 2 virus, with genes from the remaining three dengue viruses added in. Dengvaxia is based on a yellow fever virus with dengue genes added in. Takeda hopes the all-dengue design will trigger a more robust immune response.

TAK-003 Dengue Vaccine Dosage

In a phase 2 study, TAK-003 was given as a single DV 0.5 mL subcutaneous injection on Day 1 and Day 90 in the clinical trial. The onset of protection was seen after the 1st dose, with 81% VE between the 1st and 2nd doses.

TAK-003 Dengue Vaccine News

November 5, 2020 - Reuters reported 'Takeda’s dengue vaccine candidate, TAK-003, is on track for regulatory filing in Asia, Latin America, and the European Union by the end of fiscal 2020, the company said.'

July 13, 2020 - The phase 2 trial demonstrated persistence of neutralizing antibody titers against TAK-003 over three years in children and adults living in dengue-endemic countries, with limited contribution from natural infection. TAK-003 was well tolerated. At month 36, seropositivity rates were 97.3%, 98.7%, 88.0% and 56.0% for DENV-1, -2, -3 and -4, respectively. Seropositivity rates varied significantly for DENV-4 according to serostatus at baseline (89.5% in seropositives versus 21.6% in seronegatives). No vaccine-related SAEs were reported.

May 21, 2020 - The U.S. CDC issued a Level 1 Travel Alert which says 'Dengue is a risk in many parts of Central and South America, Mexico, and the Caribbean.'

March 17, 2020 - The Lancet published the 'Safety and immunogenicity of a tetravalent dengue vaccine in children aged 2–17 years: a randomized, placebo-controlled, phase 2 trial.' Between Dec 5, 2014, and Feb 13, 2015, 1800 children were randomly assigned to the following groups: two-dose primary series (n=201), one primary dose (n=398), one primary dose plus 1-year booster (n=1002), and placebo (n=199). Of them, 1479 (82%) participants completed the 48-month study. Immunogenicity endpoints were assessed in 562 participants enrolled in the immunogenicity subset, of whom 509 were included in the per-protocol subset. At month 48, antibody titers remained elevated in all TAK-003 groups compared with placebo, irrespective of baseline serostatus. At month 48, geometric mean titres were 378 (95% CI 226–632) in two-dose, 421 (285–622) in one-dose, 719 (538–960) in one-dose plus 1-year booster, and 100 (50–201) in placebo recipients against DENV 1; 1052 (732–1511), 1319 (970–1794), 1200 (927–1553), and 208 (99–437) against DENV 2; 183 (113–298), 201 (135–298), 288 (211–392), and 71 (37–139) against DENV 3; and 152 (97–239), 164 (114–236), 219 (165–290), and 46 (26–82) against DENV 4; and tetravalent seropositivity rate was 89% (79–96), 86% (80–92), 97% (93–99), and 60% (47–72), respectively. Virologically confirmed dengue was recorded in 37 (2%) TAK-003 and 13 (7%) placebo participants, with a relative risk of 0·35 (0·19–0·65). No vaccine-related serious adverse events or severe dengue virus disease were reported.

March 17, 2020 - Commentary published by The Lancet: Evaluate a tetravalent dengue vaccine by serostatus and serotype. 

November 23, 2019 - Takeda presented 18-month data from the pivotal Phase 3 Tetravalent Immunization against Dengue Efficacy Study (TIDES) trial of its dengue vaccine candidate (TAK-003) at the 68th American Society of Tropical Medicine and Hygiene (ASTMH) taking place in National Harbor, MD from November 20-24. The trial met all secondary endpoints for which there were a sufficient number of cases, looking at overall vaccine efficacy, secondary efficacy by serotype, baseline serostatus, and disease severity, including hospitalizations and severe dengue. The additional data build upon the 12-month primary efficacy endpoint data published online in the New England Journal of Medicine. Safety and efficacy will continue to be assessed over a total of 4.5 years.

November 6, 2019 - Takeda’s Dengue Vaccine Candidate Demonstrates Protection in Children Ages Four to 16 Years, Regardless of Previous Dengue Exposure. The results from this Phase 3 study, Efficacy, Safety, and Immunogenicity of Takeda's Tetravalent Dengue Vaccine (TIDES), concluded the Takeda vaccine candidate TAK-003 was efficacious against symptomatic dengue in countries in which the disease is endemic. Results demonstrated overall vaccine efficacy of 80.2% (12-month follow-up after the second dose) against virologically confirmed dengue; exploratory analyses of secondary endpoints showed 82.2% vaccine efficacy among baseline seropositive and 74.9% vaccine efficacy among baseline seronegative.

November 5, 2019 – Takeda Pharmaceutical Company announced its new manufacturing plant in Singen, Germany, for its dengue vaccine candidate, TAK-003. 

January 29, 2019 - Takeda announced TAK-003, which is in a pivotal Phase 3 trial met the primary efficacy endpoint. This first analysis of the Tetravalent Immunization against Dengue Efficacy Study (TIDES) trial showed that its investigational live-attenuated tetravalent dengue vaccine was efficacious in preventing dengue fever caused by any of the 4 serotypes of the virus. While the extensive data set review is ongoing, TAK-003 was well tolerated with no significant safety concerns to date. The TIDES trial is continuing, and additional results are expected later this year, along with results from other Phase 3 studies.

October 31, 2018 - About dengue and Takeda's dengue vaccine candidate (TAK-003).

September 7, 2016 - Takeda Initiates Global Phase 3 Clinical Trial (TIDES) of Dengue Vaccine Candidate (TAK-003).

TAK-003 Dengue Vaccine Clinical Trials

Takeda’s investigational live-attenuated tetravalent dengue vaccine candidate, TAK-003, is being studied in healthy children and adults in dengue-endemic and non-endemic countries. Its clinical development program consists of five Phase 3 trials.

Clinical Trial NCT03999996: Long-Term Safety and Antibody Persistence of TDV and Impact of a Booster Dose - Last Update Posted: June 25, 2020.

• This new Phase 3 study will look at the long-term antibody persistence and safety of Takeda's TDV in healthy adolescents and adults and assess the impact of a booster dose.

Clinical Trial NCT02747927: Efficacy, Safety, and Immunogenicity of Takeda's Tetravalent Dengue Vaccine (TDV) in Healthy Children (TIDES) - Last Update Posted: November 6, 2020.

• This Phase III, Double-Blind, Randomized, Placebo-Controlled Trial is to Investigate the Efficacy, Safety and Immunogenicity of a Tetravalent Dengue Vaccine (TDV) Administered Subcutaneously in 21,000 Healthy Children Aged 4 - 16 Years Old

Clinical Trial NCT02302066: Safety and Immunogenicity of Different Schedules of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in Healthy Participants

• TDV is being tested in this Phase 2 study to assess how different dosing schedules of the vaccine effect immunity to dengue fever in dengue-endemic countries. This study will look at the number of antibodies to dengue fever formed in people who are administered different dosing schedules of TDV.

Clinical Trial NCT01765426: Phase, 1b Study, Investigating Safety & Immunogenicity of TDV Given Intradermally by Needle or Needle-Free PharmaJet Injector

• This is an exploratory trial to assess the safety, tolerability, and immunogenicity of vaccination with a tetravalent dengue vaccine (TDV) in healthy adults delivered intradermally using the conventional needle/syringe or a needle-free PharmaJet® injector.