Vaccine Info

TAK-003 Dengue Vaccine

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October 6, 2021
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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 that causes dengue fever or Severe Dengue. TAK-003 (TDV) is based on a live-attenuated dengue serotype two virus, which provides the genetic "backbone" for all four dengue serotypes.

Takeda's current clinical development program consists of five Phase 3 trials. 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's primary endpoint, in children ages 4 to 16 years. The vaccine efficacy (VE) was 80.2% in the 12 months after the 2nd vaccine dose, 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.

On March 25, 2021, the Company announced Takeda is participating in the EMA's first-ever parallel assessment of a medicinal product for use in the European Union and through the EU-M4all (previously Article 58) procedure for countries outside of the EU. Derek Wallace, VP, Dengue Global Program Leader at Takeda, stated in a press release, "Submission of regulatory filings for our dengue vaccine candidate, TAK-003, marks an important development for people who are living in or traveling to communities burdened by the threat of dengue." Takeda intends to submit regulatory filings in Argentina, Brazil, Colombia, Indonesia, Malaysia, Mexico, Singapore, Sri Lanka, and Thailand during 2021.

On May 20, 2021, an audio review of Three Years Efficacy of Takeda's Tetravalent Dengue Vaccine Candidate was published.

The journal Clinical Infectious Disease published an ACCEPTED MANUSCRIPT on October 4, 2021: Three years efficacy and safety of Takeda's dengue vaccine candidate (TAK-003). This study concluded by stating, 'TAK-003 was efficacious against symptomatic dengue over three years. Efficacy declined over time but remained robust against hospitalized dengue.'

The TAK-003 vaccine is not currently licensed anywhere in the world. For more information, visit www.TakedaVaccines.com.

Osaka-based Takeda Pharmaceutical Company Limited (TSE: 4502, NYSE: TAK) 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.

TAK-003 Dengue Vaccine Indication

The TAK-003 vaccine candidate is indicated to prevent the Dengue virus caused by any of the four 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.

On March 17, 2020, The Lancet published two studies that concluded 'TAK-003 was well tolerated and efficacious against symptomatic dengue in children regardless of serostatus before immunization in a phase three study. However, vaccine efficacy varied by serotype, warranting continued follow-up to assess longer-term vaccine performance.' And a phase two study reported 'TAK-003 elicited antibody responses against all four serotypes, which persisted to 48 months post-vaccination, regardless of baseline serostatus.'

On May 22, 2021, Takeda confirmed TAK-003 prevented 83.6% of Hospitalizations and 62.0% of Dengue Illness Overall, With No Identified Important Safety Risks Through Three Years Following Vaccination in Ongoing Pivotal Phase 3 TIDES Trial.

On June 10, 2021, the NEJM reported, 'In 2019, a total of 413 dengue cases were probably imported to Florida, including 14 cases of severe dengue (3.4%), predominantly in the Miami area. In addition, most travel-associated patients reported recent travel to Cuba and were infected with dengue virus serotype 2 (DENV-2).

TAK-003 Dengue Vaccine Dosage

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

TAK-003 Dengue Vaccine Side Effects

The ongoing phase 3 study demonstrated rates of serious adverse events were 2.9% in the TAK-003 group and 3.5% in the placebo group during the ongoing long-term follow-up (i.e., the second half of the three years following vaccination), but none were related. Therefore, no important safety risks were identified.

TAK-003 Dengue Vaccine News

October 6, 2021 - Local media in India reported the state health department confirmed of the 13,532 tests of suspected patients carried out, 3,760 have been found positive of dengue. At present, there are 39 laboratories in Punjab doing free testing of dengue.

October 4, 2021 - Clinical Infectious Disease reported TAK-003 efficacy and safety in seronegative and seropositive participants. Its performance varies by serotype, with some decline in efficacy from first to second-year post-vaccination. This review found the cumulative efficacy after three years was 62.0% against virologically-confirmed dengue (VCD) and 83.6% against hospitalized VCD. Efficacy was 54.3% against VCD and 77.1% against hospitalized VCD in baseline seronegatives, and 65% against VCD, and 86% against hospitalized VCD in seropositives. Efficacy against VCD during the third year declined to 44.7%, while efficacy against hospitalized VCD was sustained at 70.8%. 

July 30, 2021 - Takeda said the European Medicines Agency had converted a previous accelerated review of Takeda's dengue vaccine, TAK-003, to standard assessment. As a result, the Company now expects a decision later next year instead of a potential approval by the end of March 2022.

June 4, 2021 - Medscape reported 'What really killed the Sanofi vaccine was that it acted as the primary infection, and the children produced antibodies. When they acquired a second infection, many became more ill, and there was a 0.5% increased risk for hospitalization. Ultimately, the US FDA approved Dengvaxia, but only for children who had previously been infected with dengue.

May 22, 2021 - Takeda Pharmaceutical Company today announced that its dengue vaccine candidate (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 (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.

March 25, 2021 - Takeda announced that the European Medicines Agency (EMA) had accepted the Company's filing packages for its dengue vaccine candidate (TAK-003). Takeda participates in the EMA's first-ever parallel assessment of a medicinal product for use in the European Union (EU) and through the EU-M4all (previously Article 58) procedure for countries outside the EU. Additionally, Takeda stated it intends to submit regulatory filings in Argentina, Brazil, Colombia, Indonesia, Malaysia, Mexico, Singapore, Sri Lanka, and Thailand during 2021.

March 15, 2021 - Japan-based Takeda Pharmaceutical Company Limited announced a mutual agreement with IDT Biologika GmbH ("IDT"), a contract development and manufacturing organization, to utilize capacity at IDT previously reserved for Takeda's dengue vaccine candidate (TAK-003) to manufacture the single-shot COVID-19 vaccine developed by the Janssen Pharmaceutical Companies. At the end of three months, Takeda's capacity will be returned to resume critical manufacturing for the planned launch of its dengue vaccine, subject to regulatory approvals.

March 2, 2021 - The U.S. CDC issued a Level 1 Travel Advisory, stating: Dengue is an ongoing risk in many parts of Central and South America, Mexico, and the Caribbean (map). Therefore, travelers to areas of risk should protect themselves by preventing mosquito bites.

December 15, 2020 - Study: Efficacy of a Dengue Vaccine Candidate (TAK-003) in Healthy Children and Adolescents 2 Years after Vaccination. TAK-003 demonstrated continued benefit independent of baseline serostatus in reducing dengue with some decline in efficacy during the second year. Three-year data will be essential to see if efficacy stabilizes or declines further. Takeda's tetravalent dengue vaccine (TAK-003) continued to demonstrate benefit in reducing dengue independent of baseline serostatus up to 2 years after completing vaccination with some decline in efficacy the second year in 4–16-year-olds in dengue-endemic countries.

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. In addition, 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. 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 four serotypes of the virus. In addition, while the extensive data set review is ongoing, TAK-003 was well tolerated, with no significant safety concerns to date. The TIDES trial continues, 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 studied in healthy children and adults in dengue-endemic and non-endemic countries. Its clinical development program consists of Phase III, Double-Blind, Randomized, Placebo-Controlled Trial to Investigate the Efficacy, Safety, and Immunogenicity of a Tetravalent Dengue Vaccine (TDV) Administered Subcutaneously in Healthy Children Aged 4 - 16 Years Old - Last updated on August 18, 2021.

Clinical Trials