Rotavirus Vaccine RIX4414 (Rotarix™)

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Abstract
Rotavirus vaccine RIX4414 is an oral vaccine composed of a monovalent, live, attenuated, human rotavirus strain of G1P[8] type. RIX4414 vaccination in infants aged 6–17 weeks at enrolment provided protection against rotavirus gastroenteritis (RVGE) of any severity and high-level protection against severe RVGE requiring hospitalization in large, randomized clinical trials conducted in a wide range of geographic regions. Protective efficacy was evident over the period (2 months) between the first and second doses of vaccine, and the protection afforded by the full two-dose course was sustained for at least 2 years, the limit to which efficacy was assessed. RIX4414 displayed protective efficacy against the common rotavirus G, P[8] types (G1P[8], G3P[8], G4P[8], and G9P[8]) and the fully heterotypic G2P[4] type. RIX4414 did not interfere with other common childhood injectable immunizations when administered concomitantly, suggesting that it should be possible to integrate the vaccine into most routine childhood vaccination schedules, including those still using oral poliovirus vaccine. RIX4414 was generally well tolerated and there was no evidence of an increased risk of intussusception. Although dependent on many factors, including prevalent infecting strains, efficacy rates, and vaccine costs, pharmacoeconomic analyses suggest that mass immunization with RIX4414 would be cost effective in many countries, especially when assessed from the societal perspective. Therefore, rotavirus vaccine RIX4414 offers a highly effective control strategy for reducing the burden of RVGE in infants. In placebo-controlled, phase II studies conducted in North America, Latin America, Asia, and Europe, rotavirus vaccine RIX4414 displayed good immunogenicity in infants aged 5–17 weeks. Seroconversion (defined as the development of a serum anti-rotavirus IgA antibody concentration ≥20 units/mL) 1–2 months after the second dose of RIX4414 occurred in 65–96% of infants compared with Haemophilus influenzae type b, and Streptococcus pneumoniae conjugate, did not result in any interference with seroprotection rates for the vaccines. In a large, phase III trial, the concomitant administration of RIX4414 and oral poliovirus vaccine did not result in interference with the immune response to either vaccine. Vaccination of infants with RIX4414 provided effective protection against RVGE in a number of phase III, randomized, double-blind, placebo-controlled, multicenter trials conducted in Asia, Europe, Latin America, and South Africa in infants generally aged 6–17 weeks at enrolment. The protective efficacy of RIX4414 in the first year after vaccination was 82–96% against severe RVGE, 85–100% against severe RVGE requiring hospitalization, and 67% and 87% against RVGE of any severity in the two trials assessing this parameter. The respective efficacy rates in the second year after vaccination were 81–96%, 83–96%, and 79%, indicating that protective immunity was sustained through the second epidemic season. The protective efficacy of RIX4414 appeared to increase with increasing severity of RVGE and was apparent from the first dose. In one study, the protective efficacy against RVGE of any severity was 90% between the first and second doses of RIX4414, a mean duration of 61 days. The protective efficacy of RIX4414 against severe RVGE was 83–100% for RVGE caused by rotavirus of G1P[8] type, 82–100% for RVGE caused by non-G1, P[8] rotavirus types, and 44–86% for RVGE caused by rotavirus of G2P[4] type. The respective type-specific protective efficacies against RVGE of any severity were 90–96%, 73–90%, and 58–62%. Rotavirus vaccine RIX4414 was generally well tolerated by healthy infants in clinical trials. The most common adverse events occurring within 8 days of administering either dose of RIX4414 were irritability, cough/runny nose, fever, loss of appetite, vomiting, and diarrhea; these events occurred at a similar frequency in RIX4414 and placebo recipients. Most adverse events were of mild to moderate severity. The incidence of serious adverse events was similar in RIX4414 and placebo recipients. There was no evidence of an increased risk for intussusception. Various modelled cost-effectiveness analyses performed from the perspective of the healthcare system projected that national immunization programs would be cost effective in Brazil, Italy, Australia, and Uzbekistan, but not in England/Wales, the UK, and France, while that performed in Belgium was marginal. From the societal perspective, which considers also the cost of lost productivity on the part of caregivers, all analyses for all countries projected that vaccination programs with RIX4414 would be cost effective or even cost saving. However, these cost-effectiveness analyses are subject to a number of limitations related to assumptions used in the models, not least of which is extrapolation of clinical trial efficacy data to local situations.

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