Despite being declared globally eradicated nearly 25 years ago, the smallpox virus still poses a public threat from bioterrorism, and biotech companies are pursuing products that counter the vaccine's side effects.

One such product, developed as vaccinia hyperimmune globulin by Cangene Corp. and as vaccinia immune globulin by DynPort Vaccine Co., is awaiting FDA approval and could help military personnel and other U.S. citizens better tolerate the vaccine - on Tuesday, Cangene filed its biologics license application, while DynPort received FDA acceptance of its BLA filed in May.

The two products are identical, said John Langstaff, president, CEO and director of Winnipeg, Manitoba-based Cangene. "DynCorp produces it for the U.S. military, while ours is for the [Centers for Disease Control and Prevention] and [Department of Health and Human Services]," he told BioWorld Today.

The World Health Organization declared smallpox globally eradicated in 1980, a few years after the last diagnosis of the disease. However, terrorist attacks in the U.S. in 2001 brought forward concerns that terrorists might try to get their hands on the limited scientific samples that remain. Therefore, military personnel began taking the vaccine again as a precautionary measure.

"One of the problems with the smallpox vaccine is that it's a live virus that's used," said David Woodland, a senior faculty member with the Trudeau Institute, a nonprofit biomedical research organization based in Saranac Lake, N.Y. "This makes it a really effective vaccine, because when you give the vaccine you actually give people a very mild form of the disease, and your body makes a very powerful effect to that. But you can get very bad side effects, especially if a person is immunocompromised."

According to the Centers for Disease Control and Prevention (CDC), about 1,000 people in every 1 million vaccinated experience serious reactions, such as a vaccinia rash, or a toxic and allergic rash that needs medical attention. Less serious reactions include soreness where the vaccine was administered, large and sore glands in the armpits, a low fever and trouble sleeping or conducting daily tasks. In rare cases, between 14 and 52 people per 1 million vaccinated have life-threatening reactions, including eczema vaccinatum, progressive vaccinia or postvaccinal encephalitis. Data from recent smallpox vaccinations have suggested a causal association with myopericarditis, symptoms of which include chest pain and shortness of breath.

A vaccine that does not use a live virus could eventually be developed, Woodland told BioWorld Today.

"Smallpox is the kind of disease that would be very easily prevented by a safe vaccine," he said. "The problem is we've never developed one and it takes a long, long time to develop a vaccine.

"So in the future we'll have absolutely wonderful vaccines against smallpox. Right now, we don't have them. We have this old vaccine, which is very effective, but has side effects."

Cangene began working on its product before the terrorist attacks in 2001, but discussions with the CDC accelerated following the terrorist attacks of Sept. 11.

"We started working largely on our own," Langstaff said, but talks with the CDC "picked up after 2001, especially after the anthrax attack in the United States."

The two parties formed a five-year supply and development agreement in 2002.

Cangene's BLA mostly is based on animal studies and some work in humans, but the product was never tested in a Phase III trial because the smallpox vaccine is not given anymore to a large population. In certain cases, the FDA permits BLA filings without extensive clinical work.

"This goes under the Bioterrorism Act and some of the changes that the FDA made in their policy for drugs that could not be tested in humans," Langstaff said.

He expects the FDA will have a decision on the product within six months. The product has fast-track designation, allowing for a rolling review of the BLA.

"This product has already been stockpiled by the CDC," Langstaff said.

DynPort's BLA consists partially of Phase I data that showed no serious adverse events among 33 healthy volunteers that each received a 100-mg dose per kilogram of body weight. A previous study also showed no serious adverse events in 78 healthy volunteers receiving doses up to 500 mg per kilogram of body weight.

If approved, vaccinia immune globulin would be DynPort's first licensed product. The company is a unit of El Segundo, Calif.-based Computer Sciences Corp., which acquired DynCorp, of Reston, Va., last year. DynPort initially evolved as a joint venture of DynCorp and London-based Porton International plc.

DynPort also is working on an improved cell-cultured smallpox vaccine (CCSV). Last year, it reported Phase I data showing that 350 volunteers exhibited a positive response to either CCSV or the historic calf lymph-produced smallpox vaccine. However, the incidence of vaccine-related fatigue, application site rash, increased temperature, headache, lymphangitis and nausea was at least 8 percent less common for volunteers receiving Dynport's vaccine.

DynPort's vaccinia immune globulin was manufactured from plasma donations of military personnel previously vaccinated against smallpox. Like Cangene's hyperimmune product, it contains antibodies specific to the vaccinia virus. Hyperimmunes are highly purified specialty antibodies made from human plasma.

Aside from working on its smallpox vaccine product, Cangene began recruiting patients this week in a trial for WinRho SDF to treat dengue hemorrhagic fever in the Philippines.

The company's stock (TSE:CNJ) dropped C10 cents on Tuesday, to close at C$9.25. Computer Sciences' stock (NYSE:CSC) dropped 88 cents, to close at $46.20.

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