Merck has filed for Rotateq approval with regulatory agencies in more than 50 countries.

A Universal Infection

Rotavirus is so contagious that it infects virtually every child in the world by the age of three, regardless of their socioeconomic situation and sanitary conditions.

This first infection typically primes the body’s immune system to recognize the virus for the rest of the individual’s lifetime, rendering the person invulnerable to it.

As such, babies and young children develop rotavirus diarrhea. Infection very rarely leads to death in industrialized countries because patients with serious symptoms are quickly and effectively rehydrated.

Rotavirus causes just 20 to 40 deaths annually in the United States from about 50,000 to 70,000 hospital admissions.

But in the developing world, half a million infants die annually from the virus—about one every minute—due to poor delivery of a treatment or it coming too late.

Long and Torturous

The search for a rotavirus vaccine has had a troubled history. Somewhat ironically, when the first rotavirus vaccine approval appeared imminent in 1998, a review in the journal Nature described its path through clinical trials as “long and torturous.” Little did the reviewers know what the future held.

This vaccine, called RotaShield, was tested by Wyeth in more than 15,000 infants in Finland, Venezuela, and the U.S. during the 1990s.

In June 1998, the results of these trials convinced the U.S. Advisory Committee on Immunization Practices to recommend infants born in the country receive three doses of RotaShield when they reached the ages of two, four, and six months.

In October of the following year, after a million and a half doses had been administered, the recommendation was withdrawn and RotaShield was taken off the market.

Data analyzed by the Atlanta-based Centers for Disease Control and Prevention (CDC) suggested a link between the vaccine and a gut problem called intussusception, where the bowel folds in on itself.

The situation aroused a great deal of dismay. The estimated risk of intussusception for inoculated children calculated by the CDC was just one in 12,000.

Developed countries saw little point in immunizing babies when the risk posed by infection was so small. However, the leaders of developing countries were dealing with a very different risk profile.

They found themselves having to decide whether to accept a vaccine deemed too unsafe for the U.S. market, an idea that eventually proved untenable, or blowing the opportunity to reduce infant mortality at home.

Vaccines Hit the Bottom Line

The New England Journal of Medicine’s editorial praises Merck and Glaxo for picking up the baton after it became evident that an entirely new vaccine was needed.

“Despite the prospect that other live oral rotavirus vaccines might also be associated with intussusception and despite the expense of conducting large-scale clinical trials for safety, two manufacturers accepted the challenge,” said the editorial.

Both trials demonstrated no significant difference in the risk of intussusception between the groups of infants immunized with the experimental products and those who took placebos.

“As these vaccines become licensed and used in Europe, the United States, and many other countries, global interest will focus next on the effect these vaccines will have on reducing the number of clinic visits and hospitalizations, as well as economic costs, in industrialized countries and hospitalizations for diarrhea and deaths among children in the developing world,” said the editorial.

After a period of flaking interest, the vaccine market has enjoyed a compound annual growth rate of more than 25 percent between 1999 and 2003, according to Datamonitor.

A November 2005 review in the journal Nature estimated global vaccines revenues rose from $3.5 million to $8.8 billion over these four years, and predicted ongoing double-digit sales growth.

Much of the recent enthusiasm in the space has centered on the potential for an outbreak of pandemic influenza.

This has prompted a recent spate of buying among the world’s five largest vaccine makers, all of whom have increased capacity either through acquisitions or by building new production facilities from scratch (see Novartis Buys Chiron).