Wyeth-Lederle was not the only pharmaceutical company working on a rotavirus in the 1990s. Both Merck and GlaxoSmithKline were actively in the development stages of a vaccine. On February 3, 2006, the FDA approved Merck’s RotaTeq live oral rotavirus vaccine for use in infants six to 32 weeks for the prevention of rotavirus gastroenteritis caused by serotypes G1, G2, G3, and G4. Data submitted to the FDA by Merck indicated that the vaccine also induced antibodies against a selection of rotavirus serotypes that contained P1.
Two pre-licensing clinical trials examined the vaccine’s efficacy against rotavirus gastroenteritis. One study reported an overall vaccine efficacy of 74 percent through the first year after vaccination. The second study examined the vaccine’s efficacy against naturally occurring rotavirus gastroenteritis caused by the serotypes contained in the vaccine. In this study, Merck reported the vaccine to have an efficacy of 72.5 percent while the FDA reported an efficacy of 71 percent.
While RotaTeq was tested against a placebo in pre-licensing clinical trials, both groups received all routinely recommended vaccines at the same time. These vaccines included COMVAX (Hepatitis B and HIB), INFANRIX (DTaP), IPOL (inactivated polio) and PREVNAR (pneumococcal). According to the clinical data provided by Merck to the FDA, the incidence of diarrhea, vomiting, otitis media (ear infection), nasopharyngitis, and bronchospasm were statistically higher among infants in the RotaTeq group versus those in the placebo control group.
Merck also reported that no increased risk of intussusception was seen between day 42 and day 60 in the RotaTeq group compared to the placebo group and no clustering of cases occurred within a 7- day or 14- day period post vaccination. Six cases of intussusception occurred in the RotaTeq group compared to five cases in the placebo control group. Other serious adverse event reported in pre-licensing clinical trials included seizures, urinary tract infections, gastroenteritis, bronchiolitis, pneumonia, and pyrexia.
Fifty-two deaths (25 in the RotaTeq group versus 27 in the control group) occurred among the approximately 70,000 infants who participated in the phase 3 clinical trials. Sudden Infant Death Syndrome (SIDS) was the most common cause of death. Other causes included meningitis, bronchopneumonia, pyelonephritis, motor vehicle accidents, injuries and one death from intussusception. The intussusception death occurred 99 days post RotaTeq vaccination.
Vaccine virus shedding and transmission was also studied prior to the vaccine’s licensure and it was reported to occur in nine percent of cases. Nearly all cases occurred after the first vaccine dose and the longest time point at which shedding occurred following vaccination was at 15 days. Horizontal transmission, however, was not evaluated by Merck during pre-licensing clinical trials.
