| briandeer.com | AIDS VACCINE FAILURE

VaxGen company attacks AidsVax critics, accusing them of "conflicts of interest"

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

On February 24 2003, VaxGen revealed that its phase III US trial of AidsVax had failed. In the previous month, it published an "editorial review" in the journal Aids (2003, 17:147-156), titled Candidate HIV/AIDS vaccines: lessons learned from the World's first phase III efficacy trials.

Notwithstanding almost universal scientific criticism - dating as far back as the 1980s - that the technology in AidsVax couldn't prevent HIV-1 infection but would only prosper on political grounds - and the federal prosecution of the review's second author, Dr William L Heyward, on whose behalf the company paid a $32,500 fine - in two of the article's 17 sections VaxGen accuses those who correctly predicted the vaccine's failure of having hidden agendas and conflicts of interest. These allegations, including a claim that Aids activists opposed investment in vaccine research (which would benefit those uninfected by HIV) are not evidenced by VaxGen and are strenuously denied.

Despite these lengthy sections, and a development timeline, no explanation is given in the 10-page paper for the decision by biotech behemoth Genentech Inc, which pioneered and owned the AidsVax technology, to give it up.

Taking risk: government, activists and industry

In the early 1990s the United States government, through the National Institutes of Health (NIH), worked with industry and shared some of the expenses of HIV vaccine development. In 1994, two envelope-based recombinant vaccines had completed phase II testing and met the government's criteria to advance to phase III trials. But at the time, a constellation of forces influenced the NIH to alter the phase III advancement criteria and decision was made not to sponsor the phase III trials. The decision was based on political, financial, and scientific grounds. Although both vaccines had protected chimpanzees from large intravenous challenges of HIV-1, there was concern that the vaccines may not protect humans.

The NIH formed a scientific committee that reviewed all of the data and recommended advancement to phase III. In response, some vocal AIDS activists objected. Their concern was that government support of a large vaccine study would divert funds away from their priority of therapeutic drug research and development. In addition, some NIH-supported scientists were concerned that diversion of funds to support vaccine clinical trials would limit the money available for their basic research.

The opposition of these two constituencies, together with the opinion of some that a better candidate vaccine, a canarypox vector 'prime' followed by a gp120 'boost'[, was just around the corner, led the NIH with input from yet another committee to ultimately decide to not support the phase III trials [12]. This decision was a setback to AIDS vaccine development and left industry with the perception that the government was not a reliable development partner.

Lesson: If the government and its constituents truly desire to stimulate vaccine development, then they must form reliable partnerships that can withstand and confront the controversy and risks, both financial and political, which are required for the development of an HIV vaccine.

Paying for development: influence of 'vaccine experts'

Without government funding, VaxGen had to look for alternative ways to raise the millions of dollars needed to complete the re-design of the vaccine and to conduct the phase III trials. In the absence of government or foundation support, VaxGen turned to private investors. Importantly, these investors, many seeing the potential profit, proved to be less adverse to risk. But potential investors, not having vaccine expertise, rely on academic researchers to help guide them in their investment decisions. On the surface, this is reasonable. Potential investors will logically turn to people with vaccine expertise before they invest in a vaccine venture.

Unfortunately, the difference between academic research and industry biologic development is considerable and not always appreciated by the research community. The difference between the process required to generate the latest bench-top research experiment and the industry process required to produce a candidate biologic for Food and Drug Administration (FDA) approval are often extreme and unconnected. Specifically, the actual value of the latest bench-top research cannot often be determined for years since it must advance through the phases of product development before becoming a licensed product. Unfortunately, many of the researchers exploring these futuristic advances have no experience in the real process of vaccine development and, thus, do not understand the difference between research and development.

VaxGen's review article briefly detours to criticize over-optimistic laboratory researchers who in the company's view undermine the field by "predicting a successful AIDS vaccine in the near future" (that isn't AidsVax), before returning to its target:

The comments of leaders in the vaccine field can be multiple. For example: (i) 'chimpanzees are not a good model' despite the fact that this primate is the only laboratory animal susceptible to HIV-1 and most likely the original source of HIV-1 infection in the wild; (ii) 'antibodies induced by gp120 do not neutralize primary isolates' despite the fact that no validation of this assay as a predictor of protection has been provided. Indeed, sera from chimpanzees that were protected against a 'primary isolate' challenge could not neutralize HIV-1 in the primary isolate neutralization assay that was claimed to predict protection [12]; finally (iii) 'recruitment of 5000 MSM volunteers will deplete the pool of volunteers for other trials', despite the fact that many more MSM are eligible for such studies [13].

Lesson: Industry, governments, and investors must choose advisors with broad expertise and experience and not be misled by fads or the research 'flavor of the week'. Without solid guidance from a broad-based scientific group, free from conflicts of interest, future investors will be unable to judge the potential value of a product and appropriately support industry to develop an effective HIV vaccine. Making such decisions in the highly visible and politically heated field such as AIDS is especially challenging.

The two references given in these sections are solely to lay publications: [12} Thomas P, Big Shot, New York, Public Affairs, 2001, and [13] The Wall Street Journal, June 3 1998.

Big Shot, by a health newsletter editor, is written from the perspective of VaxGen and Genentech, falsifies material and essentially constitutes a longer version of the VaxGen review, omitting material that might embarrass the companies. VaxGen staff are referred to throughout by their first names and are ascribed the most uplifting motivations. Others are not treated so benevolently:

"At NIH, Fauci and Gallo were among the first intramural researchers to see that Aids, like cancer in the 1970s, could be the raw material of a new empire. There were discoveries - and careers - to be made. [123]"

"John Moore was... one of the self-appointed 'next generation' of Aids experts [298]"

"At fifty-two, Don was the leanest and most tightly-wound of the Genentech foursome, with a forelock of dark blond hair that flopped down over his bright blue eyes [200]... When they finally did get around to talking about gp120, Don asked Bob [Nowinski] what would motivate him to work towards a vaccine against Aids. 'And he said, "I've got three small kids."' [276]"

The VaxGen editorial review was received for publication on November 25 2002 and bore the following author attribution: Donald P Francis, William L Heyward, Vladimir Popovic, Patti Orozco-Cronin, Karin Orelind, Carolyn Gee, Adrian Hirsch, Tina Ippolito, Aimee Luck, Michael Longhi, Vineeta Gulati, Nathan Winslow, Marc Gurwith, Frank Sinangil and Phillip W Berman. It is inferred that the three authors with middle initials given are primarily responsible for the content.

Go to the VaxGen - AidsVax index