The U.S. licensing approval of Acambis's smallpox vaccine over the weekend was the firm's last step in fulfilling a contract with the government, but was a major leap forward for the company in finalizing a proposed agreement with the feds.
ACAM2000, a live, attenuated vaccinia virus smallpox vaccine, is indicated for active immunization for people at high risk for the infection.
The product is a clonal isolate of Dryvax, a vaccine manufactured by Wyeth Laboratories and used in the campaign to eradicate smallpox.
Wyeth stopped making Dryvax in 1982. However, the U.S. government kept at least 15 million doses in dry-freeze storage since then in case the disease reappeared.
The last U.S. case of smallpox occurred in 1949. The last known case of the disease was reported in Somalia in 1977. The World Health Organization declared the disease eradicated in 1980.
Because the U.S. government ceased smallpox immunizations in the early 1970s, at least half of the nation's population has no immunity to the disease.
In the late 1990s, the government recognized that the country potentially was vulnerable to a naturally occurring outbreak or a bioterrorism attack of smallpox and began rebuilding its smallpox vaccine program.
As part of the government's emergency preparedness plan, it contracted with Acambis to develop ACAM2000 under an investigational new drug application.
The company's first U.S. contract was for 40 million doses. But after the 9/11 attacks, the number of doses under the contract was increased substantially.
Acambis has supplied 192.5 million doses of ACAM2000 to the U.S., which is being stored by the CDC's Strategic National Stockpile (SNS) program - a federal repository of vaccines, anti-infectives, chemical antidotes, antitoxins and other medical supplies designed to supplement and resupply state and local public health agencies in the event of a national emergency.
The firm also has supplied an undisclosed number of doses to at least 14 other nations, spokeswoman Lyndsay Wright told BioWorld Today.
Acambis, which splits its headquarters between Cambridge, UK, and Cambridge, Mass., is in negotiations with the government for a "warm-base manufacturing" contract to establish production capability of ACAM2000 on U.S. soil, Wright said.
The bulk production of ACAM2000, which previously was completed for the U.S. at a facility owned by Baxter Pharmaceuticals in Austria, will be moved to a facility in Canton, Mass., she said, adding that the purification activities, which previously were completed in Massachusetts, will remain in that state.
Acambis also has purchased a facility in Rockville, Md., from BioReliance Corp. for the freeze-drying and vial fill finishing production activities for ACAM2000, Wright noted.
Moving the entire production of ACAM2000 to the U.S. will ensure that the nation quickly can reinforce and maintain its smallpox vaccine supply, she said. It also ensures that there is long-term production capability for the vaccine within U.S. borders.
Under the warm-base manufacturing contract, which has not yet been finalized, Acambis will complete annual production runs to ensure that facilities, equipment and personnel are up to speed, Wright said.
The vaccine doses produced annually will be included in the SNS.
The military also plans to use ACAM2000 for its smallpox vaccination program to immunize soldiers serving in high-threat areas, such as Korea.
Col. Randall G. Anderson of the Department of Defense Military Vaccine Agency said that the military plans to transition to ACAM2000 "over a period of time."
Once transitioned, he told BioWorld Today, DOD will no longer use Dryvax, which is in limited supply.
The government has yet to decide whether the military's supply of ACAM2000 under the pending warm-base contract will be stored by the CDC, Wright noted.
A spokesperson for the Department of Health and Human Services said that the 192.5 million doses in the SNS are planned for use in the civilian population, if needed.
Analyst Robin Campbell, of U.K.-based Jeffries International Ltd., said that the warm-base contract "is still not a dead certainty" for Acambis.
Award of the contract, he said, is "critical for near-term revenues" and will provide the firm with reasonable cash to pursue future strategies.
Campbell predicted that the contract will not be finalized before the end of the year.
He noted that Acambis's second-quarter figures are due to be reported on Sept. 25.
An FDA panel in May voted 11-0 in favor of approving ACAM2000.
ACAM2000 was studied in two populations: those who had never been vaccinated for smallpox and those who had received smallpox vaccination many years earlier.
The percentage of unvaccinated persons who developed a successful immunization reaction was similar to that of Dryvax, according to the FDA. ACAM2000 also was found to be acceptable as a booster in those previously vaccinated for smallpox.
The labeling for ACAM2000 carries a black-box warning alerting clinicians and the public about serious risks associated with the vaccine, including myocarditis, pericarditis, encephalitis, encephalomyelitis, encephalopathy, progressive vaccinia, generalized vaccinia, severe vaccinial skin infections, eczema vaccinatum resulting in permanent sequelae or death, ocular complications, blindness, fetal death and erythema multiforme major, including a life-threatening condition known as Stevens-Johnson syndrome.
The FDA also required Acambis to develop a risk minimization action plan for ACAM2000, which includes the distribution of a consumer-friendly medication guide to patients receiving the vaccine.
The med guide is the first to be distributed with a vaccine.
Acambis plans to conduct Phase IV studies once the military has started using the vaccine, Wright noted. The FDA approval letter calls for such studies involving up to 15,000 soldiers.