Rotateq (rotavirus vaccine, live oral pentavalent)

RotaTeq is a live, orally administered pentavalent vaccine containing 5 reassorted rotaviruses. The vaccine is designed to target the viral serotypes which are most common and most frequently associated with severe gastroenteritis.

RotaTeq is specifically indicated for the prevention of rotavirus gastroenteritis in infants and children caused by the rotavirus serotypes G1, G2, G3, and G4 in infants between the ages of 6 to 32 weeks.

RotaTeq is supplied as a pale yellow clear suspension for oral delivery. A standard regimen is administered as three 2 ml oral doses: the first should be administered at 6-12 weeks of age, with subsequent doses administered on 4 to 10 week intervals (the last dose should be administered before the infant reaches 32 weeks of age).

FDA Approval
Approval of RotaTeq was based on results of three phase III trials of the drug, which treated a combined 72.324 infants in 11 countries. Two of the studies, the Rotavirus Efficacy and Safety Trial (REST) and Study 007, were designed to investigate the efficacy of the drug; the third, Study 009, was designed to investigate the vaccine's safety and manufacturing consistency.

REST Study
This placebo-controlled study investigated the primary efficacy of the vaccine (n=2834), compared to placebo (n=2839). In the primary efficacy analysis (including subjects finishing the vaccination course), all-severity gastroenteritis occurred in 82 subjects in the vaccine group, compared to 315 in the placebo group (74.0% efficacy); severe rotavirus gastroenteritis occurred in 1 vaccine subject, and 51 placebo subjects (98.0% efficacy). Intent to treat (ITT) analysis (including subjects receiving at least 1 dose of the vaccine) efficacy rates in all-severity and serious enteritis were 60.0% (n=150 vs. 371) and 96.4%, (n=2 vs. 55) respectively. Secondary efficacy measures were also positive, with the vaccine significantly reducing hospitalizations for gastroenteritis due to G1, G2, G3, and G4 rotavirus infection in both full-regimen (95.8% reduction; n=6 vs. 144) and ITT (94.7%; n=10 vs. 187) populations.

Study 007
This placebo controlled study investigated the efficacy of the drug in reducing gastroenteritis due to rotavirus serotypes G1, G2, G3, or G4 during the fist viral season. Efficacy in reducing all-severity disease was 72.5% in the primary efficacy group, and 58.4% in the trial's ITT group. Efficacy in reducing incidence of severe disease for both primary and ITT populations was 100%.

Ongoing Study Commitments

• A large-scale observational post-licensure safety study to evaluate the incidence of intussusception and other safety parameters in recipients of Rotateq in approximately 44,000 subjects (adjustments to the sample size will be made based on the background rate of intussusception). The study will be designed to detect an increased risk of intussusception due to vaccine of 2.5 or greater with 80% probability.
  Protocol Submission: May 2006
  Study Start: Q3 2006
  Final Report Submission: Q4 2008
• An adequately powered non-inferiority study of the concomitant administration of Rotateq with acellular pertussis vaccine in which serological endpoints will be examined using a validated assay. The study will be powered sufficiently to detect a 1.5-fold difference in GMTs.
  First Protocol Submission: May 2006

Adverse events associated with the use of RotaTeq may include, but are not limited to, the following:

• Diarrhea
• Irritability
• Otitis Media
• Vomiting
• Nasopharyngitis
• Bronchospasm

Intussusception, a serious gastrointestinal event which has been associated with previously approved rotavirus vaccines, occurred in 6 of 34,837 subjects receiving the vaccine at day 42, and 13 subjects by day 365, compared to 5 of 34,788 receiving placebo at day 42 and 15 subjects at day 365. The difference in incidence between these groups was not statistically significant, and none of the cases through 42 days in patients receiving the vaccine occurred following a single dose (the highest-intussusception risk period for earlier vaccines).

RotatTeq is designed to elicit immune response against a broad spectrum of Rotavirus strains. The vaccine is composed of 5 strains of live reassorted rotavirus. 4 of the strains express one of the capsid proteins (G1, G2, G3, G4) from the human rotavirus parent and the attachment protein P7[5] from bovine rotavirus. The fifth strain expresses the P1[8] attachment protein from the human rotavirus strain and the G6 bovine rotavirus capsid protein.

Vesikari T, Matson DO, Dennehy P, Van Damme P, Santosham M, Rodriguez Z, Dallas MJ, Heyse JF, Goveia MG, Black SB, Shinefield HR, Christie CD, Ylitalo S, Itzler RF, Coia ML, Onorato MT, Adeyi BA, Marshall GS, Gothefors L, Campens D, Karvonen A, Watt JP, O'Brien KL, DiNubile MJ, Clark HF, Boslego JW, Offit PA, Heaton PM; Rotavirus Efficacy and Safety Trial (REST) Study Team. Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. New England Journal of Medicine 2006 Jan 5;354(1):23-33

Ranheim T, Mathis PK, Joelsson DB, Smith ME, Campbell KM, Lucas G, Barmat S, Melissen E, Benz R, Lewis JA, Chen J, Schofield T, Sitrin RD, Hennessey JP Jr. Development and application of a quantitative RT-PCR potency assay for a pentavalent rotavirus vaccine (RotaTeq). Journal of Virological Methods 2006 Feb;131(2):193-201. Epub 2005 Oct 7

Ward RL, Bernstein DI, Smith VE, Sander DS, Shaw A, Eiden JJ, Heaton P, Offit PA, Clark HF Rotavirus immunoglobulin a responses stimulated by each of 3 doses of a quadrivalent human/bovine reassortant rotavirus vaccine. Journal of Infectious Diseases 2004 Jun 15;189(12):2290-3. Epub 2004 May 25

For additional information regarding RotaTeq or Rotavirus gastroenteritis, please visit the RotaTeq web page.