Dengvaxia Adverse Reactions

Data in subjects 9 years of age or older: Summary of the safety profile: A total of approximately 20,667 subjects 9 through 60 years of age received at least one dose of the final formulation of Dengvaxia according to the claimed vaccination schedule in 13 randomized, observer-blinded, placebo-controlled Phase II to Phase III clinical studies.
The safety profile presented as follows is based on a pooled analysis including a total of 1547 subjects 18 through 60 years of age and 19,120 subjects 9 through 17 years of age. Reactogenicity was assessed in a subset of 4615 subjects, including 1547 subjects 18 through 60 years of age and 3068 subjects 9 through 17 years of age.
Safety was monitored during the first 28 days following each dose in the reactogenicity subset, and serious adverse events (SAEs), including dengue cases, were collected throughout the studies in all subjects, up to at least 6 months after the last dose of Dengvaxia. The database allowed for the detection of adverse events (AEs) occurring at a frequency of 0.1% or above.
In subjects 9 through 60 years of age, the most frequently reported ARs following any dose of Dengvaxia were headache, injection site pain, malaise and myalgia.
The ARs were usually mild to moderate in severity and of short duration (0 to 3 days). Onset was typically observed 0 to 3 days after the injection of Dengvaxia, except for fever which appeared within 14 days after the injection.
Systemic ARs tended to be less frequent after the second and third dose of Dengvaxia as compared to the first dose.
Tabulated list of adverse reactions: Adverse reactions are listed according to the following frequency categories: Very common: ≥ 10%; Common: ≥ 1% and < 10%; Uncommon: ≥ 0.1% and < 1%; Rare: ≥ 0.01% and < 0.1%; Very Rare: < 0.01%.
ARs within 28 days after any injection in subjects 9 through 60 years of age are presented in Table 7, based on safety data collected during clinical studies. (See Table 7.)

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"Very common" and "common" ARs were similar in nature for subjects 9 through 17 years of age and subjects 18 through 60 years of age, however there were differences in terms of frequency. Fever was less frequently reported in subjects 18 through 60 years of age (frequency: common) and injection site haematoma and pruritus were less frequently reported in subjects 9 through 17 years of age (frequency: uncommon).
"Uncommon" ARs were observed with the following age-group specificities: Lymphadenopathy, migraine, arthralgia and influenza-like illness were only reported in subjects 18 through 60 years of age; Urticaria was only reported in subjects 9 through 17 years of age; Upper respiratory tract infection, dizziness, oropharyngeal pain, cough, rhinorrhoea, nausea, rash and neck pain were less frequently reported in subjects 9 through 17 years of age (frequency: rare or very rare, i.e., with a frequency < 0.1%).
In phase III efficacy studies (CYD14 and CYD15), isolated neurological disorder related SAEs have been observed in subjects 8 through 11 years of age: acute polyneuropathy in one subject of 10 years of age, convulsion (reported as "seizures not specified") in one subject of 11 years of age, and acute disseminated encephalomyelitis (ADEM) in one subject aged 8 years of age. These events were isolated and therefore not listed in the tabulated list of adverse reactions as previously mentioned. These three isolated events were outside the age indication.
Hospitalized and/or clinically severe dengue fever in long-term safety follow-up data: In an exploratory analysis of up to 6 years of follow up from the first dose in three efficacy studies, an increased risk of hospitalization for dengue including clinically severe dengue (predominantly Dengue Hemorrhagic Fever grade 1 or 2 [WHO 1997]) has been observed in vaccinees with no previous dengue infection. In subjects 9-16 years of age, it was estimated that during a 5 year follow-up about 5 additional hospitalized dengue cases or 2 additional severe dengue cases per 1000 vaccinees with no previous dengue infection could occur following vaccination. Estimates from the long-term analysis suggest the onset of increased risk was mainly during the 3rd year following the first dose.
This increased risk was not observed in individuals who have been previously infected by dengue virus, where it was estimated that 15 hospitalized dengue cases or 4 severe dengue cases could be prevented per 1000 vaccinees with previous dengue infection during 5 years of follow up from the first dose.
In subjects 12-16 years of age, it was estimated that during a 5 year follow-up about 5 hospitalized dengue cases could be prevented per 10,000 vaccinees with no previous dengue infection; however 1 additional severe dengue case per 1000 vaccinees with no previous dengue infection could occur following vaccination. In the same age range, it was estimated that 11 hospitalized dengue cases or 4 severe dengue cases could be prevented per 1000 vaccinees with previous dengue infection during 5 years of follow up from the first dose. For severe dengue, the results are not meaningful due to low number of subjects combined with low disease incidence.
Paediatric data in subjects below 12 years of age, i.e., outside the age indication: In subjects 2 through 11 years of age, i.e., outside the age indication, long-term safety follow-up data showed an increased risk of dengue disease requiring hospitalization including clinically severe dengue in vaccinees with no previous dengue infection.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions to the Health Sciences Agency of Singapore via the ADR online reporting tool at www.hsa.gov.sg or to Sanofi Singapore Pharmacovigilance at PV.SIN@sanofi.com.