Washington Editor

The FDA this week issued draft guidance for companies developing drugs to treat the side effects of vaccination against smallpox with vaccinia virus.

Although it is not believed that smallpox vaccine complications requiring treatment would be widespread in the event of a terrorist attack, the agency said plans for drug development should be designed to make use of all data collected.

The draft guidance issued Wednesday summarizes appropriate nonclinical studies recommended during early drug development. It includes sections on chemistry, manufacturing and controls, nonclinical toxicology, microbiology; and clinical pharmacology. The guidance also focuses on the acquisition of in vivo data through the use of animal models, an approach that might be necessary because of the low occurrence of serious vaccinia complications in the vaccinated population.

The guidance concludes with sections addressing the acquisition of human efficacy and safety data, issues surrounding the design of clinical trials and sections detailing data-collection requirements and recommendations, along with consideration of long-term patient follow-up and special population data collection. A sample case report form is provided as an example of a data-collection format.

Before Sept. 11, 2001, smallpox essentially was a memory for most people in the U.S. Routine vaccination for the incurable, highly transmittable, often deadly disease ended in the 1970s when it was eradicated. Smallpox has a case-fatality rate of 30 percent or more and has the ability to spread in any climate or during any season, the Center for Civilian BioDefense Studies at Johns Hopkins University in Baltimore said. (See BioWorld Today, Sept. 25, 2001.)

Government officials and scientists believe the smallpox virus - among others, such as anthrax and the plague - could be used as a biological weapon.

The old vaccine used on children born before the early 1970s was developed decades ago and provides good protection, but causes a vaccinia infection at the inoculation site. Also, people who are immunosuppressed or have eczema or other skin conditions could suffer complications. Healthy people, on rare occasions, also could develop infections. (See BioWorld Today, Nov. 19, 2002.)

In September 2000, the Centers for Disease Control and Prevention in Atlanta awarded Acambis plc, of Cambridge, UK, a $343 million, 20-year deal to develop and stockpile 40 million doses of a smallpox vaccine. Post Sept. 11, Acambis received another CDC contract for 155 million doses at $428 million.

Other companies, including VaxGen Inc., of Brisbane, Calif., and Bavarian Nordic A/S, of Copenhagen, Denmark, are working on smallpox vaccines. Meanwhile, Chimerix Inc., of San Diego, won a $36.1 million grant from the National Institutes of Health to continue development of an oral antiviral drug for smallpox infections and complications resulting from vaccinations. And SIGA Technologies Inc., of New York, is developing a smallpox vaccine and a drug to treat smallpox infection. (See BioWorld Today, April 2, 2003, and Sept. 11, 2003.)

When asked if the draft guidance regulations would impact Acambis' progress on its vaccinia virus candidate, Lyndsay Wright, company communications manager in the UK, told BioWorld Today the firm has not been notified of any impact.

"As far as we are aware at the moment, we've agreed to a testing program with the FDA, and we are currently in Phase III," she said. "So the FDA has already defined what it wants us to do in Phase III trials."

The firm initiated a Phase III program in late 2003 and expects to wrap it up toward the end of the third quarter. Wright said the company anticipates filing its new drug application late in the year.

Although Acambis' smallpox vaccine is new, it is derived from the old vaccine and is believed to have a similar safety profile, Wright said.

Back at the FDA, the agency said it wants to help commercial and research sponsors plan and design appropriate studies for the development of drugs to treat such adverse events.

The guidance is available for viewing on the Federal Register. Comments and suggestions should be submitted within 60 days to Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, Md., 20852. The draft guidance is available online at http://www.fda.gov/cder/guidance/5518dft.pdf.