BioWorld International Correspondent

LONDON - Acambis plc was forced to double the number of subjects in a Phase I study of its West Nile vaccine after two adverse events forced suspension of the trial. The expansion, from 60 to 120 subjects, will delay the results until 2005.

That setback comes on top of the suspension in April of two Phase III trials of ACAM 2000, the smallpox vaccine the company is developing for the U.S. government.

The company made the West Nile announcement as it released first-quarter financial results showing suspension of the smallpox trial had pushed the company back into the red. Revenue was down from £41.8 million (US$76.3 million) in the first quarter of 2003 to £18.8 million, resulting in a pre-tax loss of £2.1 million, compared to a £9.6 million profit in the first quarter of 2003.

Acambis CEO Gordon Cameron said the loss was "an anomaly of accounting," because the suspension of the smallpox trial made it necessary to reassess at what point revenues were booked. The cash balance at March 31 was £130.1 million, up from £125 million in December.

The West Nile trial, using a Yellow Fever vaccine as a control, was stopped after two subjects, one in the active and one in the control arm, developed elevated levels of creatine phosphokinase post-vaccination. That enzyme is associated with heavy exercise.

"It turned out that both [subjects] did strenuous exercise, so it was concluded there was unlikely to be a connection with the vaccines," Cameron said.

In order to rule out the possibility of vaccine-related adverse events, the trial was extended to include a placebo arm and again is under way.

News of the delay overshadowed the release of initial data from the trial, which is the first clinical trial data for a West Nile vaccine. All subjects in the first cohort generated neutralizing antibodies within 21 days.

"The trial is now proceeding to plan, but the doubling means the timeline moves to 2005," Cameron said. "The good news is we've got early encouraging data."

Since the first outbreak in New York in 1999, West Nile virus has spread to 45 U.S. states, Canada and Central America. In 2003 there were 8,200 cases and 182 deaths. Cambridge, UK-based Acambis received a grant of $3 million toward the development of the vaccine from the National Institutes of Health in Bethesda, Md.

Recruitment to the ACAM 2000 smallpox trials remains suspended after three subjects, who had received either ACAM 2000 or the existing licensed vaccine Dryvax, developed myopericarditis, an inflammation of the heart and surrounding tissues.

Cameron noted that myopericarditis is a known side effect of Dryvax, and since the aim of the trial is to demonstrate noninferiority to Dryvax, he expects the license application for ACAM 2000 to go ahead as planned in 2005.

He added that suspension of the trial has had neither a negative nor positive effect on other potential customers. Acambis now is in advanced talks with several other governments and expects to sign more ACAM 2000 contracts by the end of the year.