Efficacy and safety of pentavalent rotavirus vaccine in Japan

Abstract

Rotavirus is the most common cause of severe gastroenteritis in children under 5 y of age. Estimates of disease burden in Japan suggest that between 26,500 and 78,000 children in this age group need hospitalization each year, resulting in a direct medical cost of 10 to 24 billion Yen. Since being introduced in routine infant immunization schedules in the United States in 2006, the oral live pentavalent rotavirus vaccine RV5 (RotaTeq™) has contributed to dramatic reductions in the incidence of rotavirus gastroenteritis (RVGE) and in health care resource utilization. This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of a 3-dose regimen of RV5 in healthy infants, age 6 to 12 weeks, at 32 sites across Japan. The results indicate that RV5 was significantly efficacious in preventing any severity [74.5% (95% confidence interval [CI]: 39.9%, 90.6%; p < 0.001)], moderate-to-severe [80.2% (95% CI: 47.4%, 94.1%)], and severe [100% (95% CI: 55.4%, 100%)] RVGE caused by viruses with serotypes contained in the vaccine. The observed cases of RVGE included rotavirus types G1 (n = 19), G3 (n = 9), G9 (n = 5) and one unspecified G serotype with P1A[8]. No G2 or G4 RVGE cases were observed, and this study was not powered to evaluate efficacy against individual serotypes. RV5 was generally safe and well tolerated in Japanese infants. These results are comparable to those observed in clinical studies conducted in other developed countries. Introduction of the vaccine in Japan may reduce disease burden and associated health care costs.

Keywords: :

• rotavirus gastroenteritis
• RVGE
• vaccine
• pentavalent rotavirus vaccine
• RV5

Disclosure of Potential Conflicts of Interest

The study was designed by Merck and Co., Inc. (including MSD, K.K., formerly Banyu Pharmaceutical Co., LTD), with substantial input from site investigators. Merck had direct oversight or participation in every stage of the study. All authors had full access to the data after study completion and unblinding, and the corresponding author had final responsibility for the decision to submit for publication.

All investigators at the study clinical sites were funded through their institution to perform the study protocol. Dr. Iwata reports having received lecture fees and grant support from MSD and GlaxoSmithKline. Drs. Nakata and Kuroki report having received lecture fees from Merck and GlaxoSmithKline. Drs. Ukae, Koizumi and Morita have no conflicts of interest. Dr. Tanaka and Mr. Shizuya are employees of MSD, K.K., a group of Merck Sharp and Dohme Corp., a subsidiary of Merck and Co., Inc. Ms. Brown and Dr. Lawrence are employees of Merck and Co., Inc. Dr. Schödel was an employee of Merck and Co., Inc., while this clinical trial was ongoing. His current affiliation is Philimmune LLC.

Acknowledgments

We are indebted to the infants and their parents or guardians who participated in this study. We would like to express our deepest appreciation to the study investigators who had committed to the enrollment of subjects into this study. The authors gratefully acknowledge Max Ciarlet’s contribution to the design of the study. We acknowledge Tonya Goodman and Karen Collins, Arbor Communications, Inc., for manuscript preparation and editorial assistance on behalf of Merck Sharp and Dohme Corp., a subsidiary of Merck and Co., Inc.