Data establishes safety profile of new GlaxoSmithKline rotavirus vaccine candidate

Jan 6 2006

Data from one of the largest infant vaccine trials ever conducted, published in the New England Journal of Medicine (NEJM), showed GlaxoSmithKline's (GSK) rotavirus vaccine candidate as effective against rotavirus disease (rotavirus gastroenteritis) in the first year of life. Rotavirus is the leading recognized cause of diarrhea-related illness and death among infants and young children.

Every year, rotavirus is associated with an estimated 25 million clinic visits, two million hospitalizations and more than 600,000 deaths worldwide among children younger than five years of age. In the United States, the Centers for Disease Control and Prevention estimates the annual rotavirus disease burden among children younger than 5 years of age as 2.7 million illnesses, resulting in 410,000 clinic visits, up to 70,000 hospitalizations and 20 to 70 deaths. The vaccine is not approved for use in the United States, however, it has been introduced as the first vaccine available to control this highly infectious disease in several markets across the world.

Results from a double-blind, placebo-controlled trial demonstrated that two doses of the rotavirus vaccine candidate given two months apart at two and four months of age, gave 85 percent protection against severe rotavirus disease and 100 percent protection against more severe disease. This protection was proven against the most common circulating strains: G1P[8], G3P[8], G4P[8] and the globally emerging G9P[8] strain. A meta-analysis considering data from this trial and other efficacy studies conducted with similar methods showed 67 percent protection against G2P[4] rotavirus disease.

The safety analysis revealed a lower incidence of serious adverse events in children receiving the rotavirus vaccine candidate compared to children receiving placebo. This finding was attributable to the lower number of gastrointestinal disease related serious adverse events in those receiving the rotavirus vaccine candidate. In addition, the safety analysis looked for, but did not find, any evidence of an increased risk for intussusception in recipients of the vaccine candidate compared to placebo. Intussusception is a complication which was observed with a previously marketed rotavirus vaccine (see editor's note). In previous studies, the most common adverse events were reported with similar frequency in both study arms; they included irritability and loss of appetite, fever, fatigue, diarrhea, vomiting, flatulence, abdominal pain and regurgitation of food.

Lead investigator Guillermo M. Ruiz-Palacios, MD, Instituto Nacional de Ciencas Medicas y Nutricion, Mexico City, Mexico commented on the data: "Rotavirus is highly contagious and infects virtually every child worldwide by the age of three years. It is the cause of a third of all hospitalizations due to gastroenteritis and is associated with a high mortality due to diarrhea in developing countries. This vaccine has been shown to be highly effective in combating this disease – it should be considered for inclusion in the routine vaccination schedules in healthcare systems around the world."

A total of 63,225 infants from 12 countries were enrolled in the study. Infants were randomly assigned to receive two oral doses of either the rotavirus vaccine candidate or placebo. From administration of the first dose until one to three months after administration of the second dose, the entire study population was followed for the assessment of intussusception and serious adverse events. In addition, a subgroup of 20,169 was followed up to one year of age for the assessment of efficacy.

Beatrice De Vos, Director Worldwide Medical Affairs, GlaxoSmithKline Biologicals, commented: "Rotavirus is highly contagious regardless of sanitary conditions. Rotavirus can be detected in about one-third of all children hospitalized for diarrhea worldwide and mortality remains highest in the developing world. The now published data give confidence that vaccination at an early age has the potential to provide protection prior to the peak incidence of rotavirus (at 6-24 months of age)."