In a new study of nearly 70,000 infants published in this week's New England Journal of Medicine, Merck's investigational vaccine Rotateq (rotavirus vaccine, live, oral, pentavalent) prevented 98 per cent of severe cases of rotavirus gastroenteritis caused by serotypes targeted by the vaccine.

Rotavirus is the most common cause of severe dehydrating gastroenteritis in infants and young children. The study also showed that Rotateq was generally well-tolerated as compared to placebo. Rotateq targets the five strains of rotavirus - G1, G2, G3, G4 and P1, responsible for more than 90 per cent of rotavirus disease around the world, states a Merck release.

"Rotavirus is a very common disease in infants and young children. Symptoms include fever, vomiting and diarrhoea and the combination of vomiting with diarrhoea from rotavirus for an extended period of time can lead to dehydration, which can result in hospitalisation and even be life threatening," said David O. Matson, principal investigator and professor of paediatrics and head of the infectious diseases section of the Centre for Paediatric Research, Eastern Virginia Medical School in Norfolk.

"In the Rotavirus Efficacy and Safety Trial (REST), Rotateq prevented rotavirus gastroenteritis and significantly reduced hospitalisations and emergency room visits from this disease," added Watson.

Among children under five years of age in the United States, rotavirus is responsible for up to 70,000 hospitalisations, an estimated 2, 50,000 ER visits and more than 4, 00,000 visits to primary care offices annually. Worldwide, rotavirus causes more than two million hospitalisations and nearly 5, 00,000 deaths each year.

"Merck has devoted more than 15 years of research to developing a vaccine to prevent the potentially serious effects of rotavirus. The results of REST demonstrated the potential benefit of Rotateq in the prevention of this common and highly contagious childhood disease that sends hundreds of thousands of children to the doctor's office every year," said Penny Heaton, senior director of clinical research at Merck Research Laboratories.

According to Heaton, Merck has filed for licensure of Rotateq in the US and more than 50 other countries, and the company plans to initiate clinical studies this year to evaluate the use of Rotateq in the developing world.

Nearly 70,000 infants from eleven nations participated in REST. REST was a double-blind, randomised, placebo-controlled study and one of the largest vaccine clinical trials ever conducted. The study began in 2001 and enrolled infants in the age range of six to 12 weeks in eleven countries.

Infants were randomly assigned to receive three doses of vaccine or placebo, given four to 10 weeks apart. Because intussusception was associated with a previously licensed rotavirus vaccine made by another manufacturer, one of the primary goals of REST was to evaluate the safety of Rotateq with respect to intussusception among vaccine and placebo recipients. Intussusception takes place when the bowel folds in on itself, causing an intestinal blockage.

Overall, 68,038 infants were vaccinated in REST - 34,035 in the vaccine group and 34,003 in the placebo group. All were monitored for serious adverse events, including intussusception, and all were followed to assess whether Rotateq could prevent hospitalisations and emergency room visits due to rotavirus disease. In addition, sub-studies within the large scale study were designed to evaluate the overall safety of Rotateq, as well as the efficacy of Rotateq against rotavirus gastroenteritis of any severity, added the release.

Rotateq prevented mild, moderate and severe rotavirus gastroenteritis. Among the 5,673 infants (2,834 in the vaccine group and 2,839 in the placebo group) included in an efficacy sub-study, Rotateq demonstrated 98 per cent efficacy against severe rotavirus gastroenteritis and 74 per cent efficacy against rotavirus gastroenteritis of any severity caused by serotypes targeted by the vaccine (G1, G2, G3, G4) as compared to placebo through the first full rotavirus season after vaccination. Overall, 397 cases of rotavirus gastroenteritis of any severity (82 in the vaccine group and 315 in the placebo group) occurred 14 or more days after the third dose through the first full rotavirus season after vaccination. Only one case of severe rotavirus gastroenteritis occurred in the vaccine group and 51 in the placebo group. In this same sub-study, Rotateq also reduced office or clinic visits for rotavirus gastroenteritis by 86 per cent.

Among the infants included in the large scale study, Rotateq reduced hospitalisations for rotavirus gastroenteritis caused by serotypes targeted by the vaccine by 96 per cent and reduced ER visits by 94 per cent. Overall, 204 infants went to the ER and 144 were hospitalised for rotavirus caused by specific serotypes targeted by the vaccine.

Merck submitted a biologics license Application (BLA) for Rotateq on April 5, 2005, and Phase III clinical trial results were reviewed last month at the US FDA Vaccines and Related Biological Products Advisory Committee. The committee unanimously agreed that the clinical data from REST and the other phase III studies supported the efficacy and safety of Rotateq.