VaxGen's midnight drop of AidsVax data catches vaccine trial critics napping

The failure of AidsVax to prevent infection with HIV - in clinical trial results published in 2003 - triggered an intense debate about the controversial product and its manufacturer, VaxGen Inc of Brisbane, California. Mail to this website, maintained by Brian Deer, shows that existing material on a VaxGen-AidsVax index is read by significant numbers. This page seeks to further inform the discussion

After a well-trailed pledge to release results of the first phase III clinical trial of a candidate vaccine against HIV-1 at 6am ET Monday July 24 2003, VaxGen Inc of Brisbane, CA, published headline information in a press release six hours early (midnight ET, 6am GMT), catching the majority of specialist reporters and scientists capable of interpreting the results, well, asleep.

So guess who wrote the headlines? Reuters and AP wire services, utilized heavily by news organizations worldwide, lead on curious VaxGen claims, mined from intense analysis of statistically questionable subgroups, that although AidsVax hadn't protected trial volunteers as a whole it had shown extraordinary efficacy among selected ethnic groups.

Here's how the Reuters agency snapped the story at 12.33 am ET:

VaxGen's AIDSVAX protects blacks, Asians

WASHINGTON, Feb 24 (Reuters) - VaxGen's AIDSVAX vaccine does not appear to protect the general population against the AIDS virus but may protect blacks and Asians, the company said on Monday.

And AP at 4.06 am ET:

Experimental AIDS Vaccine May Help Some

By PAUL ELIAS

AP Biotechnology Writer

SAN FRANCISCO -- An experimental AIDS vaccine being developed by VaxGen Inc. does not appear to protect most people from the disease, but does show promise in protecting blacks and Asians, the company said.

USA Today was given advance information on the results and, perhaps in gratitude, published a shallow puff for the company. It drew extensively on quotes from Jose Esparza at UNAIDS, who had worked closely with VaxGen vice-president Dr William Heyward, later prosecuted by the US government for channeling millions of dollars to the company while in public service at the Centers for Disease Control. Significantly, Esparza reveals that UNAIDS had for some time enjoyed priviledged access to confidential market-sensitive data.

Vaccine for AIDS appears to work

By Steve Sternberg, USA TODAY

Nearly two decades after the discovery of the AIDS virus, researchers Monday report for the first time that an AIDS vaccine can prevent infection, but with sharply different success rates depending on race.

The first full-scale human trial of the vaccine, AIDSVAX, indicates that, although the vaccine failed to protect whites and Hispanics, it appears to be effective in Asians and blacks. Blacks account for half of all new infections in the USA, federal statistics show.

"The results are fascinating and surprising," says Donald Francis, CEO of VaxGen, the Brisbane, Calif., firm that has spent 10 years and about $200 million to develop the vaccine. "We think they're scientifically and socially important. It's at least a beginning."

Jose Esparza, director of AIDS vaccine research for the Joint United Nations Programme on HIV/AIDS (UNAIDS), called the finding "probably the most important accomplishment in vaccine research in 15 years. This is the first time anyone has shown protection (against HIV) in humans, not monkeys. The results tell us that a vaccine can protect humans against HIV."

He says the vaccine's "remarkable" effectiveness in non-whites, especially blacks, "obviously has worldwide ramifications." Last year alone, 3.5 million people were infected with HIV in Sub-Saharan Africa and roughly a million in Asia. VaxGen also is conducting a study in Thailand that is expected to be done by the end of the year. Experts say the vaccine will have to be reformulated, though, to protect against the HIV strains circulating in Africa.

Phillip Berman, VaxGen's vice president for research and development and the vaccine's inventor, says researchers don't fully understand why the vaccine protected blacks and Asians but not the others in the study. Preliminary evidence from the study, Berman says, suggests that blacks and Asians mount a better antibody response than whites and Hispanics.

VaxGen researchers are studying volunteers' serum, he says, to figure out what protects blacks and Asians so they can use that information to boost the vaccine's potency.

The vaccine study involved 5,108 gay men and 309 high-risk women. The volunteers got seven injections over three years. Two volunteers received vaccine for every one who got a placebo. Although the vaccine failed to provide protection overall, it was 78.3% effective in blacks and 68% effective in Asians.

Esparza says VaxGen turned a substantial amount of data over to UNAIDS for independent statistical analysis that "confirmed the results found by VaxGen." But he added: "We have a number of unknowns here that have to be answered by more research."

The Food and Drug Administration has said it would consider approving a vaccine that was 30% effective, but the agency won't comment on products before they're approved. Neither Francis nor any other experts would predict how the agency would respond in this unprecedented situation, but they said it was unlikely the vaccine would be approved soon.

"We've discussed the findings with FDA," Francis says. "We will work with them to see what needs to be done to lead to licensure."

A more accurate picture for those who knew where to look, however, came from the New York-based International Aids Vaccine Initiative:

NEW YORK, 24 February 2003—VaxGen Inc. announced today that its investigational AIDS vaccine, AIDSVAX, although safe, did not prove effective in human trials in North America and Europe.

AIDSVAX was designed to prevent people who are uninfected with HIV from contracting the virus or developing AIDS. AIDSVAX is the first AIDS vaccine ever fully tested in humans.

In the trial, 3330 volunteers received AIDSVAX, and 1679 received a placebo (an inactive substance). The percentage of volunteers who received AIDSVAX and became infected with HIV is statistically equal to the percentage of volunteers who received the placebo and became infected with HIV. This means that the vaccine is not protective.

In response, Seth Berkley, MD, President and CEO of the International AIDS Vaccine Initiative (IAVI), released this statement:

"The news on VaxGen's AIDSVAX is disappointing, but we are not discouraged. The search for an AIDS vaccine will—and must—go on. A vaccine is the world's best hope to end the spread of a virus that infects nearly 15,000 men, women and children daily and threatens the survival of whole communities.

"Scientists remain confident that an AIDS vaccine is possible. Alternative AIDS vaccines, employing different design strategies, are now in development, and some have already entered human trials. These must move forward through further study, without delay. (More information on why an AIDS vaccine is possible and what approaches are in development.)

"The results on AIDSVAX must be further analyzed, and independently reviewed. For example, VaxGen's preliminary analysis of the small number of nonwhite volunteers suggests that there were fewer infections among black volunteers who received AIDSVAX than blacks who received the placebo. However, it is difficult to draw conclusions about what this means, given that the number of blacks in the study was so small (VaxGen's analysis is based on just 13 infections among black volunteers, 4 in the vaccine group and 9 in the placebo group). [Continues]

A similar line was taken by the Aids Vaccine Advocacy Coalition:

Vaccine Fails to Show Efficacy
Data from subgroup analysis is intriguing
But drawing conclusions would raise false hopes

NEW YORK — The AIDS Vaccine Advocacy Coalition (AVAC) today expressed disappointment that the first efficacy trial of an AIDS vaccine failed to show protection in the study population. The trial was of the vaccine candidate AIDSVAX that is made by VaxGen.

"Of course it's unfortunate that AIDSVAX did not demonstrate efficacy in the study population of over 5000 men who have sex with men and over 300 women at risk of HIV infection," said Chris Collins, Executive Director of AVAC. "But this trial should not be characterized as a failed effort. More human trials of better candidates in several countries will likely be necessary to identify an AIDS vaccine."

"The AIDSVAX results did provide surprising data in the sub-population of African American trial participants," Collins said. "But the trial simply was not designed to demonstrate efficacy in this subgroup and the numbers of participants in this group are too small to draw any conclusions about the vaccine's effects in this subpopulation."

"The African American community has been devastated by AIDS, and finding a vaccine that could protect African Americans would be truly outstanding," Collins said. "But given the overall finding, at this stage in the data analysis, it would be hazardous to jump to conclusions about what the AIDSVAX data mean for this subgroup. Such premature conclusions run the risk of raising false hopes in a world desperate for an AIDS vaccine.

Further examination, and perhaps further trials, are necessary before conclusions can be drawn."

There are over 20 other AIDS vaccine candidates in or nearing clinical trials and several are considered more promising than AIDSVAX. These candidate vaccines use multiple different approaches to protect from HIV.

"AIDS vaccine research is a long term effort," Collins said. "The North American AIDSVAX trial has been one important step in that effort."

Aids organizations quickly turned the heat up, later in the day denouncing the results announcement. See activists condemn VaxGen