OSAKA, Japan & CAMBRIDGE, Mass. - Saturday, 10. December 2022
− The European Commission Approved QDENGA (TAK-003) for Use in Individuals Four Years of Age and Olderi
− QDENGA Becomes the Only Dengue Vaccine Approved in the EU for Use in Individuals Regardless of Previous Dengue Exposurei
WIRE) -- Takeda (TSE:4502/NYSE:TAK) today announced that the European
Commission (EC) granted marketing authorization for the company’s dengue
vaccine QDENGA® (Dengue Tetravalent Vaccine [Live, Attenuated])
(TAK-003) for the prevention of dengue disease in individuals from four
years of age in the European Union (EU).i QDENGA should be used in
accordance with official recommendations. The approval follows the
positive recommendation from the European Medicines Agency’s Committee
for Medicinal Products for Human Use (CHMP) in October 2022.
the increasing ease of travel today, our once expansive world has
become that much smaller, increasing the risk of dengue disease for
those living in dengue-endemic areas and for those traveling to these
regions,” said Gary Dubin, M.D., president of the Global Vaccine
Business Unit at Takeda. “The European Commission's approval marks an
important turning point for QDENGA as we are one step closer to
achieving our aspiration to help reduce the global burden of dengue. We
are proud to introduce QDENGA in many parts of the EU, offering
healthcare providers a new tool in dengue prevention for their patients
living in the EU and traveling to endemic regions around the world.”
worldwide incidence of dengue has risen eight-fold in the past 20
years, and it continues to rise, fueled by climate change and
urbanization.ii Today, dengue threatens about half the world’s
population with a risk of infection in over 125 countries, and the
disease is endemic in most of the European overseas countries,
territories and departments located in tropical areas.ii,iii These
factors have led to events of local transmission in non-endemic areas in
continental Europe, including France, Italy, Germany and Spain.iv
Dengue is a leading cause of fever in travelers returning to Europe from
endemic countries, and the incidence of dengue among European travelers
is generally underestimated.v,vi The threat of disease is present for
more than 26 million people from Europe who typically travel to endemic
regions each year for holidays and visiting friends and family.vii
dengue prevention requires a multi-faceted approach, and previous
methods have been insufficient for a number of reasons. With the
potential for dengue to cause local outbreaks as demonstrated in several
European countries over recent years, and the threat for European
travelers visiting dengue-endemic countries, gaps exist that may put
some people at risk,” said Dr. Tomas Jelinek, Medical Director of the
Berlin Centre for Travel and Tropical Medicine and Scientific Director
of the CRM Centrum für Reisemedizin Dusseldorf. “As a clinician, it is
encouraging to have a new dengue vaccination tool available for a broad
population of my patients.”
Approval from the EC was supported by
results across 19 Phase 1, 2 and 3 trials with more than 28,000
children and adults, including four and a half years of follow-up data
from the global, pivotal Phase 3 Tetravalent Immunization against Dengue
Efficacy Study (TIDES) trial. The TIDES trial met its primary endpoint
of overall vaccine efficacy (VE) by preventing 80.2% of symptomatic
dengue cases 12 months after vaccination.viii In addition, TAK-003 met
its key secondary endpoint by preventing 90.4% of hospitalizations 18
months after vaccination.ix Efficacy varied by serotype (DENV-1 –
4).viii,ix The TIDES exploratory analyses showed that throughout the
4.5-year study follow-up, TAK-003 prevented 84% of hospitalized dengue
cases and 61% of symptomatic dengue cases in the overall population,
including both seropositive and seronegative individuals.x TAK-003 has
been generally well tolerated, with no evidence of disease enhancement
in vaccine recipients, and no important safety risks have been
identified, to date.x
QDENGA is also approved in Indonesia for
the prevention of dengue disease by any serotype in individuals six
years to 45 years of age. Takeda continues to progress regulatory
filings in other dengue-endemic countries in Asia and Latin America.
EC decision has no impact on the full year consolidated reported
forecast for the fiscal year ending March 31, 2023 (Fiscal Year 2022).
(TAK-003) is a dengue vaccine that is based on a live-attenuated dengue
serotype 2 virus, which provides the genetic “backbone” for all four
dengue virus serotypes and is designed to protect against any of these
In the European Union (EU) Member States, QDENGA is
indicated for the prevention of dengue disease in individuals from four
years of age and should be administered subcutaneously as a 0.5 mL dose
at a two-dose (0 and 3 months) schedule pursuant to approved dosing
regimen.i QDENGA should be used in accordance with official
QDENGA was assessed across a clinical
development program that included 19 Phase 1, Phase 2 and Phase 3
trials, and more than 28,000 participants, including Takeda’s pivotal
Tetravalent Immunization against Dengue Efficacy Study (TIDES) trial.
The TIDES trial met its primary endpoint of overall vaccine efficacy
(VE) against virologically-confirmed dengue (VCD) with 80.2% efficacy at
12-months follow-up.viii The trial also met all secondary endpoints for
which there were a sufficient number of dengue cases at 18-months
follow-up.ix The VE result in preventing hospitalization due to VCD
fever was 90.4%.ix Through four and a half years (54 months after the
second dose), QDENGA demonstrated continued overall protection, with
sustained overall VE of 61.2% and 84.1% VE against hospitalized dengue.x
Observations of VE varies by serotype and remained consistent with
previously reported results.x QDENGA has been generally well tolerated,
with no evidence of disease enhancement in vaccine recipients, and no
important safety risks have been identified in the TIDES trial, to
Important Safety Information
Please consult the Summary of Product Characteristics (SmPC) before prescribing.
for use: QDENGA should be administered by subcutaneous injection
preferably in the upper arm in the region of deltoid. QDENGA must not be
injected intravascularly, intradermally or intramuscularly. Vaccination
should be postponed in subjects suffering from an acute severe febrile
illness. The presence of a minor infection, such as a cold, should not
result in a deferral of vaccination. Vaccination should be preceded by a
review of the individual’s medical history (especially with regards to
previous vaccination and possible hypersensitivity reactions which
occurred after vaccination). Appropriate medical treatment and
supervision must always be readily available in the event of a rare
anaphylactic reaction following administration of the vaccine.
Anxiety-related reactions, including vasovagal reactions (syncope),
hyperventilation or stress-related reactions may occur in association
with vaccination as a psychogenic response to the needle injection. It
is important that precautions are in place to avoid injury from
fainting. A protective immune response with Qdenga may not be elicited
in all vaccinees against all serotypes of dengue virus and may decline
over time. It is currently unknown whether a lack of protection could
result in an increased severity of dengue. It is recommended to continue
personal protection measures against mosquito bites after vaccination.
Individuals should seek medical care if they develop dengue symptoms or
dengue warning signs.
Contraindications: Hypersensitivity to the
active substances or excipients listed, or to previous Qdenga dose.
Individuals with congenital or acquired immune deficiency, including
immunosuppressive therapies such as chemotherapy or high doses of
systemic corticosteroids (eg, 20 mg/day or 2 mg/kg body weight/day of
prednisone for 2 weeks or more) within 4 weeks prior to vaccination.
Individuals with symptomatic HIV infection or asymptomatic HIV infection
with impaired immune function. Pregnant and breast-feeding women.
Reactions: Most frequently reported reactions in subjects 4 to 60 years
of age were injection site pain (50%), headache (35%), myalgia (31%),
injection site erythema (27%), malaise (24%), asthenia (20%), and fever
(11%). Very common: (≥1/10 of subjects): upper respiratory tract
infectiona, decreased appetitec, irritabilityc, headache, somnolencec,
myalgia, injection site pain, injection site erythema, malaise,
asthenia, fever. Common (≥1/100 to <1/10): nasopharyngitis,
pharyngotonsillitisb, arthralgia, injection site swelling, injection
site bruisinge, injection site prurituse, influenza like illness.
aIncludes upper respiratory tract infection and viral upper respiratory
tract infection. bIncludes pharyngotonsillitis and tonsillitis.
cCollected in children below 6 years of age in clinical studies.
dIncludes rash, viral rash, rash maculopapular, and rash pruritic.
eReported in adults in clinical studies. Refer to the SmPC for details
on full side effect profile and interactions.
▼ This medicinal
product is subject to additional monitoring. This will allow quick
identification of new safety information. Healthcare professionals are
asked to report any suspected adverse reactions. See Section 4.8 of the
SmPC for how to report adverse reactions.
For full prescribing information, please see the Summary of Product Characteristics (SmPC) for QDENGA®▼.
Please consult with your local regulatory agency for any approved labeling in your country.
drug information contained herein is intended to disclose corporate
information. Nothing contained in this document should be considered a
solicitation, promotion, or indication for any prescription drug,
including those currently under development.
is a mosquito-borne viral disease that spreads rapidly around the world
and was one of the WHO’s top 10 threats to global health in 2019.ii,xii
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.ii The prevalence of individual serotypes varies across different
geographies, countries, regions, seasons and over time.xiii Recovery
from infection by one serotype provides lifelong immunity against only
that serotype, and later exposure to any of the remaining serotypes is
associated with an increased risk of severe disease.ii
About the Phase 3 TIDES (DEN-301) Trial
double-blind, randomized, placebo-controlled Phase 3 Tetravalent
Immunization 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.viii
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.viii Study participants were
randomized 2:1 to receive two doses of TAK-003 0.5 mL or placebo on
Months 0 and 3, administered subcutaneously.viii 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.viii 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.ix Part 3 evaluated VE and long-term safety by following
participants for an additional two and a half to three years, as per WHO
recommendations.xiv 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.xiv
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.xiv 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.
Takeda’s Commitment to Vaccines
prevent 3.5 to 5 million deaths each year and have transformed global
public health.xv 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 flu
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
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.
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i Takeda. QDENGA Summary of Product Characteristics. Retrieved December 2022.
ii World Health Organization. Dengue and Severe Dengue. January 2022. Retrieved December 2022.
iii European Centre for Disease Prevention and Control (ECDC). Factsheet about dengue. November 2021. Retrieved December 2022.
European Centre for Disease Prevention and Control (ECDC).
Autochthonous transmission of dengue virus in EU/EEA, 2010-present.
October 2022. Retrieved December 2022.
v Bulugahapitiya, U.,
Siyambalapitiya, S., Seneviratne, S. L., & Fernando, D. J. (2007).
Dengue fever in travellers: A challenge for European physicians.
European journal of internal medicine, 18(3), 185–192.
vi T. Jelinek, N.
Mühlberger, G. Harms, et al. European Network on Surveillance of
Imported Infectious Diseases, Epidemiology and Clinical Features of
Imported Dengue Fever in Europe: Sentinel Surveillance Data from
TropNetEurop, Clin Inf Dis. Volume 35, Issue 9, 1 November 2002, Pages
vii Travel data from: UNWTO. Yearbook of Tourism Statistics, Data 2014-2018. 2020.
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.
x Tricou, V. Efficacy
and Safety of Takeda’s Tetravalent Dengue Vaccine Candidate (TAK-003)
After 4.5 Years of Follow-Up. Presented at the 8th Northern European
Conference of Travel Medicine; June 2022.
xi Huang CY-H, et al.
Genetic and phenotypic characterization of manufacturing seeds for
tetravalent dengue vaccine (DENVax). PLoS Negl Trop Dis. 2013;7:e2243.
xii World Health Organization. Ten threats to global health in 2019. January 2019. December 2022.
xiii Guzman MG, et al. Dengue: a continuing global threat. Nature Reviews Microbiology. 2010;8:S7-S16.
Efficacy, Safety and Immunogenicity of Takeda’s Tetravalent Dengue
Vaccine (TDV) in Healthy Children (TIDES). Retrieved December 2022.
xv World Health Organization. Vaccines and immunization. October 2022. Retrieved December 2022.
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