Acambis plc has suspended the recruitment of additional volunteers into its Phase 3 clinical trials involving its investigational smallpox vaccine ACAM2000 and Dryvax, the comparator smallpox vaccine being used in the trials. This precautionary measure was taken after three suspected myopericarditis cases were discovered in both ACAM2000 and Dryvax-vaccinated subjects. Myopericarditis is a condition where there is an inflammation of the heart and surrounding tissues.

Acambis' independent Data and Safety Monitoring Board (DSMB) recommended that enrolment into the studies be suspended pending further review and until additional data can be obtained. As a precaution, Acambis has also suspended another, smaller study vaccinating individuals with ACAM2000 and Dryvax. Once this analysis is completed, including the involvement of the DSMB, Acambis will be enlisting the assistance of the US Food and Drug Administration and the U.S. Centers for Disease Control and Prevention to determine the next steps.

The two Phase 3 clinical trials are designed to compare the safety, tolerability and efficacy of ACAM2000 with Dryvax, the currently licensed smallpox vaccine that was widely used during the worldwide smallpox eradication program. In each of these trials the ratio of individuals receiving ACAM2000 and Dryvax is 3:1.

The first Phase 3 trial involves subjects that have never received smallpox vaccine. To date, 1,132 individuals have been vaccinated. Three cases of suspected myopericarditis have been recognized in this study. The DSMB has indicated that the cases occurred in both ACAM2000 and Dryvax-vaccinated subjects.

The second Phase 3 trial involves subjects that have previously been vaccinated against smallpox. To date, 1,752 individuals have been vaccinated. No cases of myopericarditis have been recognized in this study to date.

Additional smaller studies involving ACAM2000 and Dryvax have identified two other possible cases of myopericarditis. These cases are also being actively investigated and followed up.

Findings from the U.S smallpox vaccination program for civilians and the military revealed data supporting a causal association between myopericarditis and smallpox vaccinations. An ongoing investigation is occurring to determine if there is any relationship between the smallpox vaccine and myopericarditis, and individuals with a diagnosis of a heart condition have been temporarily deferred from receiving the smallpox vaccine.

These cardiac adverse events represented an important and, apparently, previously under-recognized complication of vaccination. As a result, Acambis instituted an intensive level of safety monitoring of subjects in its Phase 3 trials. This includes frequent active monitoring of cardiac symptoms, serial EKG evaluations, and blood tests for cardiac injury.

In this setting, it is difficult to determine whether the three recent cases reported suggest a higher frequency of cardiac adverse events than expected from previous recent experience. Surveillance for adverse events both during the era of routine vaccination and in the recent civilian and military vaccination programs was not as intense as is being performed in these controlled clinical trials. Nevertheless, subject safety is paramount and therefore the decision was made to suspend enrolment in these trials.

Acambis has informed all investigators to suspend recruiting and vaccinations in the trials and will be providing new information on the safety of smallpox vaccination as it becomes available. Investigators also have been informed to notify all subjects who have been vaccinated as part of the trials of the updated information concerning myopericarditis-related risks of vaccination. All volunteers will continue to be monitored as planned, and will be given full information from the ongoing analysis when completed.