European Commission approves Qdenga as second dengue virus vaccine

Globally incidence of infection of dengue virus has increased 8-fold in the past 20 years and has become endemic in most tropical European Overseas Countries and Territories.

The European Commission has approved the dengue tetravalent vaccine (live, attenuated [TAK-003]) for prevention of dengue virus (DENV) in individuals aged ≥4 years regardless of prior DENV exposure. Dengvaxia was first vaccine authorised in 2018 to protect against dengue in people who have been previously infected.

Branded Qdenga , it is second dengue vaccine to be approved for use in the European Union. The approval of the vaccine was based on clinical trials in >28,000 children and adults, including 4.5 years of follow-up data from the pivotal phase 3 trial.

"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.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

"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.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.

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.xi

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