BioWorld International Correspondent

Last week's decision by the National Institute of Allergy and Infectious Diseases in the U.S. to award two MVA smallpox vaccine development contracts could result in a legal skirmish between the two recipients as they battle it out for the main prize - a tender to supply up to 30 million doses worth, according to one analyst estimate, a minimum of US$150 million.

The contest pits Denmark's Bavarian Nordic A/S, which has already shipped large quantities of its MVA smallpox vaccine to the German armed forces, against UK firm Acambis plc, which won two major contracts to supply an earlier generation of smallpox vaccines to the U.S. (See BioWorld International, Dec. 5, 2001.)

Each has received three-year contracts worth a combined US$20 million in the first year in order to conduct preclinical and clinical development and to prepare plans for large-scale manufacturing. The endgame is a government tender, which is expected to be published later this year, to supply a stockpile of smallpox vaccines based on the MVA technology.

Copenhagen-based Bavarian Nordic has filed four patent applications covering different aspects of MVA production, which it is planning to invoke. Those, said CEO Peter Wulff, will make it "extremely difficult" for Acambis to produce MVA smallpox vaccine. Three of the patent applications, he told BioWorld International, arose from in-house work, while the company licensed the fourth from Anton Mayr of Ludwig Maximilians Universit t in Munich, Germany. The company is planning shortly to communicate its intentions to Cambridge-based Acambis. "They will receive a letter from us," Wulff said.

Acambis declined to comment on the issue.

MVA is based on a Modified Vaccinia Ankara vector, which was originally developed in Germany in the 1950s and 1960s. The strain is highly attenuated and does not replicate in human cells, so it is regarded as safe for administration to immunocompromised patients, children, pregnant women and other individuals who cannot tolerate the existing generation of smallpox vaccines.

Bavarian Nordic, which has a manufacturing alliance with Impfstoffwerk Dessau-Tornau GmbH (IDT), of Rosslau, Germany, claims a two- to three-year lead in this area, and said last week that its MVA-BN smallpox vaccine was entering a Phase II trial in Switzerland this month, involving 165 healthy volunteers. It has completed a Phase I trial in 86 subjects, and it is also fulfilling its first supply contract. "We already established production of MVA and we have already delivered vaccine in commercial quantities to the German army," Wulff said.

According to analyst Chris Redhead at London-based WestLB Panmure, the U.S. contest is likely to be determined on the merits of the contenders' respective production plans. "Most of the MVAs are very similar; they're not terribly different. The real issue here is not getting through the trials, but who can come up with the manufacturing," he said. Redhead is backing Acambis to win, because of its manufacturing alliance with Baxter International Inc., of Deerfield, Ill., and because of its previous success in landing large U.S. government contracts. "They've dealt with this before, they've delivered before. They have Baxter in the back seat doing the manufacture," he said.

Danish analyst Anette Rye Larsen at Carnegie Bank A/S in Copenhagen takes an opposing view. "As far as I know, Acambis has never worked with an MVA vaccine before," she said. If it does prevail, she still expects the Danish firm to take a piece of the action. "I'm 100 percent certain that Bavarian Nordic will gain some royalties from Acambis because they have a pretty strong patent position in MVA," she said.