AIDS TREATMENT NEWS Issue #183, September 17, 1993
John S. James

This article can only outline the basics of a situation described in the July 17 New Scientist as "bizarre events... descending into political farce."

The controversy started when Congress appropriated $20 million for the Department of Defense (DoD; the Army is the lead organization within DoD to conduct this research) to test a vaccine made from the gp160 protein of HIV, to treat persons already infected with the virus. Only one company, MicroGeneSys, Inc., of Meriden, Connecticut, had a gp160 product (named VaxSyn, produced by genetically engineered insect cells) with enough safety data to enter a large trial with thousands of people; most of the other vaccines which have enough data are based on gp120 instead. Leading scientists and health officials have been very concerned that Congress specified a particular product in legislation, instead of letting decisions about which drugs to test be determined by scientific review. (MicroGeneSys got the appropriation by an effective lobbying campaign, including hiring ex-Senator Russell Long of Louisiana to lobby Congress.)

The law allowed the trial to be scuttled if the National Institutes of Health, the Food and Drug Administration, and the Department of Defense agreed (within six months) that the trial as specified was not scientifically justified -- in which case the money would be used for other AIDS research instead. So NIH convened a panel of vaccine experts to decide what to do. But instead of making a formal determination against the one-vaccine trial, as the law clearly allowed, the panel instead recommended a trial comparing several different vaccines (including VaxSyn). Many of the experts believed that some of the other available treatment vaccines are more promising -- that VaxSyn should be included, but not as the only agent being tested. The Army, whose experience in AIDS vaccines is largely limited to VaxSyn, agreed to turn the money over to NIH to conduct the comparative trial. (Other possible candidates include vaccines from Genentech; from Biocine, a partnership of Chiron and Ciba-Geigy; from Immuno AG of Vienna, Austria; and from Immune Response Corporation.)

But then MicroGeneSys refused to donate its vaccine, and asked NIH to pay $10 million for it -- half of the total appropriation. Other companies agreed to donate their vaccines. NIH is unwilling to pay for the drugs which it is testing, at public expense, to the great benefit of the companies developing them -- and it was unwilling to allow this case to set a precedent which could hurt all government clinical trials in the future. (If pharmaceutical companies start charging the government for drugs its scientists want to use in trials, less could be done with the increasingly scarce Federal resources).

Because the legislation specified gp160, it was not possible to drop MicroGeneSys and proceed without any gp160 vaccine; no other gp160 vaccine was ready for such a trial, although one might be ready early next year. Because of this impasse, the money was never transferred from DoD to NIH, as both parties had agreed in principle to do. The Army proceeded with its original plan for testing the MicroGeneSys product alone. The Army also insisted that the company donate the vaccine, and MicroGeneSys then agreed to do so.

Meanwhile, the VaxSyn data used in lobbying for the Congressional appropriation, presented by Robert Redfield, M.D., of the Walter Reed Army Institute of Research, at the Amsterdam AIDS conference in 1992, has been seriously questioned. The presentation showed stabilized or reduced viral levels in patients, with statistical significance compared to natural-history controls. But not all patients had been included, for reasons that are in dispute. A later analysis, with all patients, failed to find a statistically significant difference. A spokesperson for Redfield was quoted, in an article in the September 1993 Lear's, as saying, "If the conclusion that people believe they heard in Amsterdam was that this gp160 was efficacious, or that we stabilize disease, or that we're curing patients, all of those things are incorrect." The chief statistician working on the project, Bill McCarthy, threatened to remove his name from one of the papers; recently he resigned (from the Henry M. Jackson Foundation, a nonprofit organization which does medical research for the Army); see "Key Statistician Ousted As Waxman Enters gp160 Fray," Nature, July 29, 1993.

Fortunately the Army has already obligated the $20 million to the Jackson Foundation, so the money will not be lost to AIDS research at the end of the current fiscal year (end of September) if the plan for the VaxSyn-only trial is changed.

It is not hard to see why MicroGeneSys has an incentive for testing only its vaccine. The first AIDS therapeutic vaccine to get FDA approval could be worth a billion dollars or more. If only one vaccine starts phase III testing, no other will have enough data to be a candidate for approval at the time the Army test ends; the FDA will have to approve VaxSyn or nothing. But if the other vaccines were tested, one or more of them might prove significantly better, and then VaxSyn might not be approved at all.

The public loss from this result is equally clear. First, thousands of people with HIV will receive a vaccine which many experts believe is less promising than other available candidates, in a trial which a panel of leading vaccine experts concluded should not be run as currently planned. And the way MicroGeneSys could benefit from having its vaccine tested alone would be through the loss or delay of other vaccines which are as good or better, which is likely to adversely affect hundreds of thousands of people.

What You Can Do

This article only sketches some of the elements of the gp160 treatment-vaccine controversy. Much more information has been published in Science, Nature, New Scientist, and major newspapers.

Three AIDS organizations (Treatment Action Group [TAG], ACT UP/New York Treatment + Data Committee, and the AIDS Action Council) are now investigating both administrative and legislative alternatives to letting the VaxSyn-only trial go forward as now planned. But time is very short, and they need to know what people think should be done. They have distributed the following survey, asking people which of the following options are acceptable, and in which order, as well as which are unacceptable:

1. Allow the Army to proceed with a comparison of gp160 vs. placebo in a phase III trial with clinical endpoints.

2. Implement the NIH/FDA panel's recommended multi-product, placebo-controlled large trial with clinical endpoints, mandating that sponsors provide vaccine free.

2a. If MicroGeneSys remains unwilling to guarantee free drug for the full duration of the trial, instruct trial organizers to consider Immuno AG's mammalian-cell based gp160, safety data on which will be in by January.

3. Allow the Army to redirect the $20 million to other AIDS research programs:

3a. Mandate ad hoc external peer review for the disbursement of AIDS awards by the Army with this $20 million, as will be done with the Army's $210 million breast cancer appropriation.

3b. Specify that the money be spent on therapeutic research.

3c. Specify that it be spent on vaccine research.

3d. Specify that it be spent on basic research.

4. Other (please specify).

Fax your answers (or any other comments) to TAG at 212/260- 8561. Or leave them a phone message at 212/260-0300.

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