West Coast Editor

Two months after selling some of the royalty rights to its rotavirus vaccine so the company could focus on other programs, Avant Immunotherapeutics Inc. reported preliminary success in Phase II with its vaccine for another diarrheal disease, cholera, in infants and children.

Avant's stock (NASDAQ:AVAN) closed Tuesday at $1.41, up 3 cents after trading as high as $1.56.

The single-dose, oral vaccine already had been shown to work in adults. The latest results show it to be well tolerated and highly effective in children aged 9 months to 5 years, with 77 percent generating immune responses.

Most significant were findings related to vaccinated children under 2 years old, "the ones that die at the highest rate," noted Una Ryan, president and CEO of Needham, Mass.-based Avant. "There is nothing approved for those children."

The vaccine, called CholeraGarde, could become part of routine pediatric immunization in regions where cholera is endemic, she said.

"We're going to be making it ourselves, so we will start manufacturing later this year for further trials to be started in 2006," Ryan said. An end-of-Phase-II meeting with the FDA is likely to take place before the end of this year, she said.

Taking part in the two-phase study were 120 infants (9 months to 23 months in age) and 120 children (2 years to 5 years old). The first phase at an in-patient facility investigated two different dose levels of the vaccine vs. placebo, followed by an outpatient phase that studied only the higher dose vs. placebo.

Sixty participants in each age group were included in the in-patient portion of the study. Twenty children got the reduced dose, 20 received the full dose, and 20 received placebo, consisting of buffer only.

The outpatient portion of the study was carried out in 60 participants from each age group, half of whom received the full dose of vaccine and half the placebo. In those participants vaccinated with the full dose, 70 percent of infants and 84 percent of children showed levels of immune responses that correlate well with protection from cholera, and when the results are grouped together, the responder frequency is 77 percent.

Detailed results from the adult portion of the study have been published electronically and will appear in the August 15, 2005, print issue of Journal of Infectious Diseases, and data from the pediatric portion will be presented at a scientific meeting yet to be determined.

CholeraGarde is the most advanced in a portfolio of single-dose, oral vaccines in development by Avant, and is based on the Peru-15 attenuated strain. The compound is also being tested against the common O1 strain of V. cholerae.

"There have been only five pandemics through the ages," Ryan said. "We believe the entire current pandemic is this Peru-15 strain," although another vaccine strain could be developed in a "couple of years" if necessary - more quickly than CholeraGarde was brought into being.

"We took a long time because we were depending on outside payers," she said. "When you let the NIH or the Gates Foundation do the work for you and they're willing to pay, you do it on their timeline."

The double-blind, randomized, placebo-controlled study was conducted at the Centre for Health and Population Research of the International Centre for Diarrheal Disease Research, Bangladesh, in collaboration with the International Vaccine Institute (IVI), Korea. The trial was sponsored by the Diseases of the Most Impoverished Program of the IVI, which is funded by the Bill and Melinda Gates Foundation.

In May, Avant sold for $61 million an interest in the net royalty of Rotarix to Paul Royalty Fund II LP, from Paul Capital Partners. Rotavirus kills about 600,000 children worldwide each year, and Avant's partner, London-based GlaxoSmithKline plc, has filed for approval in about 30 countries, expecting to launch it in Latin American and Asia Pacific regions this year and the European Union within 12 months. Rotarix was approved in Mexico last year. (See BioWorld Today, May 19, 2005.)

"We didn't sell all the royalties," Ryan pointed out. "We kept the upside, above certain caps," and GSK recently came out with "some enormous numbers for rotavirus in the developing world. They see the annual market at over $2 billion for Rotarix. That was bigger, frankly, than we had calculated in house."

It also could mean a brighter picture for the cholera vaccine.

"We've always calculated it to be about $50 million, so we thought it was a small market, but now I'm starting to wonder," she said.

The vaccine, Ryan noted, will benefit travelers as well as afflicted children in poor countries.

"To be honest, only when you talk about markets do you see progress. I don't want to be disparaging and I do send money myself, but obviously charity hasn't done that much," she said, adding that Avant is "trying to make a profit, but not a disgusting one. We've got to have a business model, we're a public company. That [profit] we would expect to make in our travelers' portion."

Other money could come from children's vaccinations in other lands, but the complexities would have to be worked out.

"You've got to find a market, but at the same time it breaks my heart to see these children dying while we're protecting healthy, wealthy Americans," Ryan said, adding that Avant intends to do both. "There's a whole new focus on the developing world."

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