Type of information: Positive opinion for the granting of a Market Authorisation in the EU
Product name: Dengvaxia®
Compound: tetravalent dengue vaccine
Therapeutic area: Infectious diseases
Action mechanism: vaccine
Company: Sanofi Pasteur (France)
- prevention of dengue caused by dengue virus serotypes 1, 2, 3 and 4 in people who are between 9 and 45 years old, live in an endemic area and already had a prior dengue virus infection
- • On October 19, 2018, the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended granting a marketing authorisation for Dengvaxia® (dengue tetravalent vaccine (live, attenuated)), for the prevention of dengue caused by dengue virus serotypes 1, 2, 3 and 4 in people who are between 9 and 45 years old, live in an endemic area and already had a prior dengue virus infection.
- There are four types of dengue virus and people living in a dengue-endemic area can have several dengue infections in their lifetime. No specific treatments for dengue exist and prevention is mainly limited to the environmental management of mosquitoes. There is currently no vaccine available for dengue in the EU. Dengue is by far the most common mosquito-borne viral disease affecting people worldwide (mainly in tropical areas); tens of millions of cases occur each year resulting in approximately 20,000-25,000 deaths, mainly in children1.
- The approved indication excludes the populations of the EU mainland and territories outside tropical areas since dengue is not endemic in these regions. However, a number of EU territories, mainly overseas, are situated in endemic areas, and these territories could benefit from this vaccine.
- The benefits and safety of Dengvaxia® have been evaluated in 31 clinical studies conducted mostly in dengue endemic areas (Latin America and Asia Pacific). Together, these trials included over 41,000 participants aged 9 months to 60 years receiving at least one dose of the vaccine. The overall available data demonstrate that for people between 9 and 45 years of age, the vaccine has positive effects in preventing symptomatic and severe dengue disease in people who have had previous dengue infection and live in endemic areas. In people who have never had dengue, there is an increased risk of clinically severe dengue disease leading to hospitalisation when vaccinees are subsequently infected with dengue virus. The CHMP therefore recommends limiting the use of the vaccine to individuals with prior dengue virus infection, for whom laboratory confirmation of the previous infection is available before vaccination. In addition, because there are no safety, immunogenicity or efficacy data to support vaccination of individuals living in non-endemic areas and travelling to endemic areas, vaccination of these individuals is not recommended.
- A number of additional risk minimisation measures will be put in place, such as educational material for physicians and a guide for healthcare professionals. Use of the vaccine should be according to official recommendation from Member States.
- • On November 29, 2017, Sanofi announced that the company will ask health authorities to update information provided to physicians and patients on its dengue vaccine Dengvaxia® in countries where it is approved. The request is based on a new analysis of long-term clinical trial data, which found differences in vaccine performance based on prior dengue infection. Based on up to six years of clinical data, the new analysis evaluated long-term safety and efficacy of Dengvaxia® in people who had been infected with dengue prior to vaccination and those who had not. The analysis confirmed that Dengvaxia® provides persistent protective benefit against dengue fever in those who had prior infection. For those not previously infected by dengue virus, however, the analysis found that in the longer term, more cases of severe disease could occur following vaccination upon a subsequent dengue infection.
- Based on the new analysis, Sanofi will propose that national regulatory agencies update the prescribing information, known as the label in many countries, requesting that healthcare professionals assess the likelihood of prior dengue infection in an individual before vaccinating. Vaccination should only be recommended when the potential benefits outweigh the potential risks (in countries with high burden of dengue disease). For individuals who have not been previously infected by dengue virus, vaccination should not be recommended.
- The Sanofi label proposal will be reviewed by national regulatory agencies in each of the countries where the vaccine is registered or under registration. Following their review, each agency might amend the company proposed label.• On April 15th, 2016, Sanofi and its vaccines global business unit Sanofi Pasteur, announced that the Strategic Advisory Group of Experts on Immunization (SAGE) has issued its recommendations to the WHO on the use of Dengvaxia® dengue vaccine. The SAGE advises that countries with high dengue transmission consider introduction of the dengue vaccine as part of an integrated disease prevention strategy including vector control to effectively lower their dengue disease burden. Successful introduction of dengue immunization alongside other prevention efforts should help endemic countries to achieve the WHO objectives to reduce dengue morbidity by 25% and mortality by 50% by 2020. The recommendations from the SAGE are based on the technical review of clinical data from 25 clinical studies conducted in 15 different endemic and non-endemic countries around the world, including more than 40,000 study participants.
- • On December 28, 2015, Sanofi Pasteur announced that Brazil has granted regulatory approval to Dengvaxia®, representing the third successful licensure of the dengue vaccine, which was also approved in Mexico and the Philippines earlier this month. The Brazilian regulatory authorities ANVISA approved Dengvaxia®, tetravalent dengue vaccine, for the prevention of disease caused by all four dengue types in individuals from 9-45 years of age living in endemic areas. Dengue continues to hit hard in Brazil with over 1.4 million Brazilians directly affected by the disease during this year's outbreak season alone. Up to 70% of dengue cases in Brazil are reported in individuals 9 years and older, a highly mobile and socially active segment of the population who contributes to the spread of the disease within communities. Dengvaxia® was shown to reduce dengue due to all four serotypes in two-thirds of the participants and prevent 8 out of 10 hospitalizations due to dengue and up to 93% of severe dengue cases.
- • On December 22, 2015, Sanofi Pasteur, the vaccines division of Sanofi, announced that the Philippines have granted marketing approval to Dengvaxia®, making it the first vaccine to be licensed for the prevention of dengue in Asia. The Philippines’ Food and Drug Administration approved Dengvaxia®, tetravalent dengue vaccine, for the prevention of disease caused by all four dengue types in individuals from 9-45 years of age living in endemic areas.
- • On December 9, 2015, Sanofi Pasteur, the vaccines division of Sanofi, announced that the Mexican authorities have granted marketing authorization to Dengvaxia®, making it the first vaccine to be licensed in the world for the prevention of dengue. The Federal Commission for the Protection against Sanitary Risks (COFEPRIS) has approved Dengvaxia®, tetravalent dengue vaccine, for the prevention of disease caused by all four dengue virus serotypes in preadolescents, adolescents and adults, 9 to 45 years of age living in endemic areas. The COFEPRIS approval of Dengvaxia® is based on results from an extensive clinical development program involving over 40,000 people of different ages, geographic and epidemiological settings, and ethnic and socio-economic backgrounds living in 15 countries. Dengue-endemic regions of Mexico participated in all three phases of the clinical development program for the vaccine.
- Regulatory review processes for Dengvaxia® are continuing in other endemic countries. Manufacturing of Dengvaxia® has already started at vaccine facilities in France and first doses are already produced. Sanofi Pasteur remains committed to introducing Dengvaxia® first in countries where dengue is a major public health priority.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
Favourable opinion UE: 2018-10-19
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: