The European Commission approved QDENGA (TAK-003) for use in individuals four years of age
and older 1
QDENGA becomes the only dengue vaccine approved in the EU for use in individuals regardless
of previous dengue exposure
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.
“With 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.”
The worldwide incidence of dengue has risen eight-fold in the past 20 years, and it continues to rise,
fueled by climate change and urbanization. 2 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 , 3 These factors
have led to events of local transmission in non-endemic areas in continental Europe, including
France, Italy, Germany and Spain. 4 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. 5 , 6 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. 7
“Effective 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. 8 In addition, TAK-003 met its key secondary endpoint by
preventing 90.4% of hospitalizations 18 months after vaccination. 9 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. 10 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.
The EC decision has no impact on the full year consolidated reported forecast for the fiscal year
ending March 31, 2023 (Fiscal Year 2022).
About QDENGA
QDENGA (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 serotypes. 11
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 recommendations.
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 date. x
Important Safety Information
Please consult the Summary of Product Characteristics (SmPC) before prescribing.
Guidance 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.
Adverse 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
infection a , decreased appetite c , irritability c , headache, somnolence c ,
myalgia, injection site pain, injection site erythema, malaise, asthenia, fever. Common (≥1/100 to
<1/10): nasopharyngitis, pharyngotonsillitis b , arthralgia, injection site swelling, injection site
bruising e , injection site pruritus e , influenza like illness. a Includes upper respiratory tract infection and
viral upper respiratory tract infection. b Includes pharyngotonsillitis and tonsillitis. c Collected in
children below 6 years of age in clinical studies. d Includes rash, viral rash, rash maculopapular, and
rash pruritic. e Reported in adults in clinical studies. Refer to the SmPC for details on full side effect
profile and interactions.
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.
The 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.
About Dengue
Dengue 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 , 12 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. 13
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
The 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
▼ 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.
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. 14 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
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. 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
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 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 www.Takeda.com/what-we-do/areas-of-focus/vaccines/.
About Takeda
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.