VaxGen Inc announced initial results from the first of its three-year, multi-national, randomized, double-blind, placebo-controlled Phase III trials of AIDSVAX (rgp120) to prevent HIV infection.
The study did not show a statistically significant reduction of HIV infection within the study population as a whole, which was the primary endpoint of the trial. However, the study did show a statistically significant reduction of HIV infection in certain vaccinated groups. Protection appeared to correlate with the higher level of vaccine-induced neutralizing antibodies observed in these groups, according to Michael Para, a principal investigator in the study.
The initial results reported in this news release are subject to additional analysis. A more detailed analysis is expected to be presented at the Keystone Symposia on HIV, March 29 to April 4. The full results of the trial will be reviewed with the U.S. Food and Drug Administration (FDA) over the coming months.
The results presented here are based on trial volunteers who received at least the primary course of three injections of either vaccine or placebo. Recognizing the limitations of subgroup analyses, the separate analysis of efficacy in subgroups was pre-specified in the statistical analysis plan. The statistical analysis plan was reviewed in advance by the FDA and its suggestions were incorporated prior to unblinding of the data.
Although the subgroup sample sizes were relatively small compared to the entire study sample, the results are statistically significant. With regard to ethnic minorities in the trial, there is less than a 1% possibility that the observed difference in infection rates could have occurred by chance. There is less than a 2% possibility that the observed difference in infection rates among black volunteers could have occurred by chance. In addition to the results in those receiving three doses, the reduction in infection in individuals who received at least one dose of vaccine or placebo were similar and also statistically significant. This analysis is known as "intent-to-treat".
Trial data indicate that black and Asian volunteers appeared to produce higher levels of antibodies against HIV. White and Hispanic volunteers appeared to develop consistently lower levels of protective antibodies following vaccination. VaxGen intends to conduct additional analyses to confirm if there was a direct correlation between the level of antibodies and the prevention of infection.
"This is the first time we have specific numbers to suggest that a vaccine has prevented HIV infection in humans," said Phillip Berman, VaxGen's senior vice president of Research and Development and inventor of the vaccine. "We're not sure yet why certain groups have a better immune response, but these preliminary results indicate that a surface-protein vaccine that stimulates neutralizing antibodies correlates with prevention of infection."
The results also indicate that AIDSVAX is well tolerated and has a high safety profile. Vaccine recipients had a slightly higher rate of pain, swelling and tenderness at the injection site compared to placebo recipients.
An independent Data and Safety Monitoring Board (DSMB) consisting of prominent scientists, researchers, ethicists and a biostatistician oversaw the trial. "VaxGen's conduct of this trial lived up to the highest standards of scientific integrity," said Walter R. Dowdle, Chairman of the DSMB and former deputy director of the U.S. Centers for Disease Control and Prevention (CDC).
Dowdle is one of several independent researchers who have taken part in reviewing the trial data. The CDC participated in the statistical analysis, and the resulting data were reviewed by Dowdle and four independent clinical researchers: Donald Burke, from the Johns Hopkins School of Public Health; Neil Flynn, from the University of California at Davis; Donald Forthal, from the University of California at Irvine; and Michael Para, from Ohio State College of Medicine.
AIDSVAX is composed of a recombinant form of the protein (gp120) on the surface of HIV and is produced in mammalian cell culture. It includes two HIV subtype B antigens: MN and GNE8. The candidate vaccine cannot cause HIV infection since it contains no genetic material from the virus. Made through recombinant DNA technology, it contains non-infectious, genetically engineered proteins (rgp120) that mimic proteins on the surface of two strains of HIV subtype B. This subtype is prevalent in North America, Europe, Australia, Japan and Puerto Rico.