FDA approves MMR-V combination vaccine

October 2005

The FDA has approved a new combination vaccine against measles-mumps-rubella-varicella (MMR-V; Proquad, Oka/Merck).

The agency approved MMR-V for children aged 12 months to 12 years if a second dose of MMR vaccine is to be administered. It combines two other Merck vaccines – MMR-II and Varivax.

“The approval of [MMR-V] makes it more likely that more children can gain protection against these four diseases because fewer shots can potentially mean better compliance,” Henry Shinefield, MD, clinical professor of pediatrics and dermatology at University of California, San Francisco School of Medicine and clinical investigator of MMR-V, said in a press release.

“We’ve been waiting for this for quite awhile,” Samuel L. Katz, MD, the Wilburt Cornell Davison Professor and chairman emeritus of pediatrics at Duke University, told Infectious Diseases in Children.

Members of the Advisory Committee on Immunization Practices (ACIP) did not recommend a second dose of varicella vaccine at their meeting in June because some members felt that if MMR-V received approval, it would affect their decision.

Second dose?

Katz said some of the concerns about a second dose of varicella vaccine were related to cost. “It sort of makes moot the discussion you heard at the last meeting [of the ACIP], whether there should be a second shot of varicella vaccine,” Katz said. “I think a lot of people felt that perhaps the cost of the second visit and the injection and the trouble of bringing kids back again would be the problem, and that maybe it wasn’t cost-effective.”

Katz, who sits on the ACIP as a liaison for the Infectious Diseases Society of America, said the vaccine would likely come up for recommendations at the committee’s meeting later this month.

How the recommendations are worded will be interesting to see, Katz said, and he speculated that the language might be permissive in allowing pediatricians to choose whether to substitute MMR and varicella vaccines with the MMR-V combination vaccine.

“My expectation is that most practicing pediatricians will opt for MMR-V for the two doses,” Katz said. “We have heard that the cost of MMR-V will be only $10 more than the price of the two (MMR and varicella) vaccines purchased seperately.”

The CDC’s childhood immunization schedule recommends that children receive their first dose of MMR and varicella after 12 months of age, with varicella catch-up between the ages of 24 months and 18 years. The CDC recommends a second dose of MMR for 4- to 6-year-olds, and children should complete both doses before age 12, according to the schedule.

About MMR-V

Merck filed an application with the FDA for approval of MMR-V in August 2004. The application included results from studies evaluating immunogenicity, antibody persistence and safety of MMR-V compared with its component vaccines.

Researchers studied immunogenicity in 5,835 healthy children aged 12 months to 6 years with a negative clinical history of MMR-V. The children participated in five randomized trials. In these trials, the immunogenicity of MMR-V was similar to its individual component vaccines, Merck officials said in a statement.

In four randomized trials that included 5,446 healthy children aged 12 to 23 months who received MMR-V, vaccine response rates for MMR-V were similar to the rates induced by the concomitant administration of single doses of the MMR vaccine and varicella vaccine at separate injection sites in 2,038 children. Results showed that following a single dose of MMR-V, the immune response rate was 97.4% for measles, 95.8% to 98.8% for mumps, 98.5% for rubella and 91.2% for varicella. The duration of protection from MMR-V infections after vaccination is unknown.

In two of the four trials, 1,035 of the children received a second dose approximately three months after their first. The proportion of initially seronegative vaccinees with positive serological responses following two doses was 99.4% for measles, 99.9% for mumps, 98.3% for rubella and 99.4% for varicella. The rates of adverse events after the second dose were similar to or lower than those seen with the first dose. Fever rate, for example, was lower after the second dose than after the first.

Researchers conducted a clinical trial of 799 healthy children aged 4 to 6 who had received the component vaccines. In this study, 399 children received MMR-V and placebo, 205 received the MMR vaccine and placebo concomitantly at separate injection sites and 195 received MMR and varicella vaccines concomitantly at separate injection sites. Following MMR-V, the seropositivity rate was 99.2% for measles, 99.5% for mumps, 100% for rubella and 98.9% for varicella.

The vaccine’s safety profile was similar to administration of its component vaccines as well. Clinical efficacy has not yet been studied.

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• Dr. Katz is a member of Merck’s Vaccine Advisory Board.