Takeda UK Ltd. announces MHRA approval for dengue virus vaccine candidate Qdenga®▼

• The MHRA has granted marketing authorisation[i] for Takeda's vaccine candidate Qdenga®▼ (Dengue Tetravalent Vaccine [Live, Attenuated]) for active immunisation against dengue infection in individuals from four years of age.   
• The decision from the MHRA will enable eligible individuals from the UK, who are travelling to dengue endemic regions, to benefit from a vaccine that has the potential to offer protection against dengue illness and hospitalisation, regardless of an individual's previous dengue exposure.[ii]
• Following the MHRA decision, the next step will involve seeking recommendation from JCVI (Joint Committee on Vaccination and Immunisation) expected in summer 2023.
• Dengue exists in more than 125 countries worldwide[iii] and is second only to Malaria as a diagnosed cause of fever among travellers returning to Europe.[iv]  

LONDON, Feb. 6, 2023 /PRNewswire/ -- Takeda UK Ltd. today announced that the Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorisation for Qdenga®▼ (Dengue Tetravalent Vaccine [Live, Attenuated]), for active immunisation against dengue infection in individuals from four years of age.[i] Qdenga® is currently the only approved vaccine in the UK for the prevention of dengue fever regardless of previous dengue exposure.[i]

Dengue is the fastest spreading mosquito-borne virus[v] and was recognised by the World Health Organization (WHO) in 2019 as one of the top ten threats to global health [ii],[vi]. An estimated 3.9 billion people around the globe – about half of the world's population – are currently at risk of dengue[iii] and it is now endemic in more than 125 countries[iii], causing an estimated 390 million infections[vii]  and 500,000 hospitalisations each year[viii]. Nearly 5 million (4.6) UK travellers visit dengue endemic regions every year[ix] and dengue is second only to Malaria as a diagnosed cause of fever among travellers returning to Europe[iv].

Dr. George Kassianos, a specialist in immunisations, said, "Although the UK is not an endemic country, more than 800 UK holidaymakers had their trips ruined by dengue before the pandemic, according to the ECDC, with all reported cases imported from endemic territories. Most people with dengue will not have any symptoms, some will have a mild illness with flu-like symptoms, while rarely others may go on to have a more severe form of the infection. Dengue symptoms usually last for up to seven days, so the impact for those who contract the infection while travelling abroad can be substantial. With this in mind, a pre-travel vaccination that provides an additional precautionary option to most travellers, in addition to following effective mosquito bite prevention, should be welcomed."

Dengue is predominantly spread to people through the bites of infected Aedes aegypti and Aedes albopictus mosquitoes.[x]  These mosquitoes are mostly found in urban and semi-urban areas in tropical and sub-tropical climates.[xi]

The virus consists of four different viral serotypes (DENV-1, 2, 3 and 4)[xii]; infection with one serotype can offer long-term immunity against that serotype but subsequent secondary infection with a different serotype can lead to severe disease.[xiii] In countries or regions with high dengue transmission, children tend to be the most affected and in countries with lower dengue transmission, adults are more affected.[xiv]  

The decision adopted by the MHRA follows key results from the ongoing Phase 3, double-blind, randomised, placebo-controlled TIDES trial, which evaluated the efficacy, safety and immunogenicity of the dengue tetravalent vaccine.[ii],[xv]

• Trial details: TIDES, otherwise known as the Tetravalent Immunization against Dengue Efficacy Study, assessed a two-dose schedule of the dengue tetravalent vaccine (three months apart), in more than 20,000 healthy, dengue-naive children (aged 4 to 16 years) living in dengue-endemic areas, over 3 years.[xv] 
• Study outcomes: TIDES met its primary endpoint of overall vaccine efficacy (VE) against virologically confirmed dengue (VCD) at 12-months follow-up and all secondary endpoints at 18-months follow-up, including VE against hospitalised dengue and VE in baseline seropositive and baseline seronegative individuals.[xv]
• Follow-up data: A recent 3-year follow-up exploratory analysis of TIDES data confirmed cumulative efficacy of the dengue tetravalent vaccine against VCD (62%; 95% CI 56.6-66.7) and against hospitalised VCD 83.6% (95% CI 76.8-88.4); vaccine efficacy against VCD declined during the third year but remained robust against hospitalised VCD, for the duration.[xvi]
• Safety: No important safety risks were identified during TIDES, and the trial remains Takeda Vaccines' largest interventional clinical trial to date.[xvi] In clinical studies, the 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%).[xvi] 

Simon Meadowcroft, Medical Director, Takeda UK & Ireland, commented, "We are pleased to announce this latest regulatory approval which provides the opportunity for the nearly 5 million (4.6) UK travellers who visit dengue endemic regions every year to protect themselves from infection with this disease. This is an exciting step in Takeda's mission to apply world-class expertise to develop and bring to market innovative vaccines for infectious diseases that address important unmet global public health needs. Dengue is a complex and widespread disease with half the world's population living in endemic areas. The launch of Qdenga means that for the first time those living in the UK and travelling to dengue-endemic countries, have the option of being vaccinated against infection"

Takeda UK Ltd. expects to make Qdenga® available in the UK in spring/summer 2023. Please refer to the GB Summary of Product Characteristics (SmPC) for more information.

https://mhraproducts4853.blob.core.windows.net/docs/f92e52062109c86c61e8186dceff26dafbad94c1   

Notes to Editors

About Qdenga® Dengue Tetravalent Vaccine [Live, Attenuated])
Qdenga 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. 

Qdenga is indicated for the prevention of dengue disease caused by any dengue virus serotype in individuals from four years of age and should be administered as a 0.5 mL dose at a two-dose (0 and 3 months) schedule pursuant to approved dosing regimen.[i] The use of Qdenga should be in accordance with official recommendations.

Please refer to the GB Summary of Product Characteristics (SmPC) for more information.

https://mhraproducts4853.blob.core.windows.net/docs/f92e52062109c86c61e8186dceff26dafbad94c1   

About Takeda Pharmaceutical Company
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), with expertise in immune and inflammatory diseases. 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.

Additional information about Takeda UK Ltd. is available through its corporate website, www.takeda.com/en-gb.   

References 

[i] Marketing Authorisations granted in 2023. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1134336/Marketing_authorisations_granted_15_January_to_31_January_2023.pdf 

[ii] BiswalS, et al. Efficacy of a Tetravalent Dengue Vaccine in Healthy Children and Adolescents. N Engl J Med 2019;381:2009–19.

[iii] WHO, Dengue and severe dengue, 2019. Accessed December 2022

[iv] Camprubí-Ferrer D et al. Causes of fever in returning travelers: a European multicenter prospective cohort study, January 2022, Journal of Travel Medicine, Volume 29. Retrieved December 2022

[v] Colón-González F et al. 'Projecting the risk of mosquito-borne diseases in a warmer and more populated world: a multi-model, multi-scenario intercomparison modelling study' Lancet Planet Health 2021. Accessed December 2022

[vi] World Health Organization. Ten threats to global health in 2019. 2019. Accessed December 2022

[vii] Bhatt S, et al.  The global distribution and burden of dengue. Accessed December 2022.

[viii]  WHO - Dengue and Severe Dengue Media Centre Factsheet, 2017. Accessed December 2022.

[ix] World Tourism Organisation (2020), Yearbook of Tourism Statistics, Data 2014 – 2018, 2020 Edition, UNWTO. Accessed December 2022.

[x] World Health Organization. Factsheet. Dengue and Severe Dengue. April 2019. Retrieved December 2022.

[xi] ECDC, Dengue annual epidemiological surveillance report for 2019 April 2021 Accessed December 2022. 

[xii] Pang VIROLOGICA SINICA 2017. Accessed December 2022.

 [xiii] World Health Organization. Factsheet. Dengue and Severe Dengue. April 2019. Retrieved December 2022.

 [xiv] Halstead S, Wilder-Smith A. Severe dengue in travelers: pathogenesis, risk and clinical management. J Travel Med 2019;26(7). Accessed December 2022.

 [xv] ClinicalTrials.gov. Efficacy, Safety and Immunogenicity of Takeda's Tetravalent Dengue Vaccine (TDV) in Healthy Children (TIDES). 2018. Accessed December 12, 2022. https://clinicaltrials.gov/ct2/show/NCT02747927?term=den-301&rank=1  

[xvi] Rivera L, et al. Three years efficacy and safety of Takeda's dengue vaccine candidate (TAK-003). Clin Infect Dis. 2021 Oct. Accessed December 2022.

[xv] Qdenga Summary of Product Characteristics. Available at: https://mhraproducts4853.blob.core.windows.net/docs/f92e52062109c86c61e8186dceff26dafbad94c1