Government contractor Acambis plc suspended recruitment of additional volunteers in a Phase III program evaluating its smallpox vaccine candidate against Dryvax, after three out of 2,800 participants showed signs of heart inflammation.
Acambis' stock (NASDAQ:ACAM) Tuesday fell $1.61, or 12.1 percent, to close at $11.75.
The Centers for Disease Control and Prevention in Atlanta has awarded Acambis contracts totaling about $500 million to develop some 209 million doses of a smallpox vaccine, which would be stockpiled and used in the event of a terrorist attack in the U.S. Acambis, with headquarters in Cambridge, UK, and facilities in Cambridge, Mass., is developing ACAM2000, a vaccina virus believed to have a safety profile similar to Dryvax, the vaccine used to eradicate smallpox in the U.S. during the 1970s.
In carrying out its clinical trials, Acambis was wise to the possibility that myopericarditis (a condition in which there is an inflammation of the heart and surrounding tissues) could surface, as a few incidents had occurred among the military and health care personnel vaccinated in the U.S. with Dryvax. Acambis responded by implementing stringent monitoring mechanisms to look for similar events in its trials, Lyndsay Wright, director of communications of Acambis in the UK, told BioWorld Today.
The company said it is difficult to determine whether the three cardiac cases suggest a higher frequency of such events among vaccine users, particularly since monitoring for such adverse events both during the era of routine vaccination and in the recent civilian and military vaccination programs was not as intense as that being performed in the controlled clinical trials.
An independent Data and Safety Monitoring Board (DSMB) recommended that enrollment in both Phase III trials be suspended pending further review and until additional data can be collected. The 5,500-patient Phase III program is designed to compare the safety, tolerability and efficacy of ACAM2000 with Dryvax.
All three suspected myopericarditis cases surfaced in the Phase III study designed to enroll people who had never received a smallpox vaccine. To date, 1,132 patients had enrolled.
Wright said the DSMB unblinded the three patients who showed symptoms, but left the remainder of the trial blinded. While the board reported that the events occurred in both treatment groups, it was not revealed whether two patients were in the Dryvax group and one was in the ACAM2000 group, or vice versa.
Meanwhile, no cases of myopericarditis have been found in the other Phase III, which has enrolled 1,752 patients who have previously received a smallpox vaccine.
The trials are expected to remain suspended over the next few months as investigators follow up with patients who have been vaccinated and the company consults with the FDA about the best method of proceeding, Wright said.
Acambis also suspended enrollment in a smaller study comparing ACAM2000 and Dryvax.
In the U.S., the CDC already is stockpiling about three-quarters of the 209 million doses it intends to purchase from Acambis, Wright said. Acambis' previous timeline of filing its biologics license application late this year has been delayed by a couple of months, to the first part of 2005, because of the heart cases.
Following Sept. 11, 2001, and the anthrax attacks in Washington, the government implemented a program whereby it could stockpile countermeasures to potential biological threats while clinical trials were ongoing.
Any side effect is serious, of course, but in the case of smallpox infection, it might not matter. Wright explained it this way: "The intention is that [the vaccine] will only be used if there is an outbreak, at which point, the threat of the disease is much greater than the threat of side effects from the vaccine."