Wall Street Journal - November 1, 2000
Thomas M. Burton, Staff Reporter

Try to suppress publication of the results, at least in the case of Immune Response Corp., a Carlsbad, Calif., biotechnology company.

In a situation raising questions about the ownership of medical research and the public's right to know, Immune Response in September took legal action to try to prevent publication of an unfavorable university study of its AIDS drug, Remune. The researchers pressed ahead anyway and their findings from the large clinical trial appear Wednesday in the latest issue of the Journal of the American Medical Association.

The study, of 2,527 patients at 77 hospitals over three years, concluded that Remune failed to show any advantage in survival or slowing progression of the disease. Remune is an experimental vaccine that contains inactivated HIV virus and is designed to help other drugs fight the AIDS-causing virus by building up a patient's immune system.

The legal action -- an arbitration proceeding -- filed by Immune Response against the University of California, San Francisco, and Prof. James O. Kahn, a leading AIDS researcher there, now seeks $7 million to $10 million in damages due to the study's publication. The company says that the article submitted to JAMA is flawed because it fails to represent the view of all the clinical investigators and doesn't include some favorable findings for Remune.

Documents in the case aren't public because the legal proceeding, filed in San Francisco, is before arbitrators instead of a judge. The arbitration panel has yet to be appointed.

Swirled up in the spat, too, are researchers at Harvard and Brown universities, and Cornell University's Henry Weill Medical College in New York, all of whom were involved in the study and sided with Dr. Kahn in seeking publication of their findings over Immune Response's objections. Pfizer Inc., whose Agouron unit has a licensing agreement under which it holds U.S. rights to Remune, says it wasn't involved in trying to suppress the study's publication. Both Pfizer and Immune Response say they still plan to develop Remune commercially and that the product is still being tested in other clinical trials. Remune was developed by the late Jonas Salk, inventor of the killed-virus polio vaccine, as a similar approach to AIDS. A co-founder of Immune Response, he died in 1995.

Dr. Kahn says it is common that researchers, sometimes in contracts they sign with a corporate sponsor of research, agree not to publish results if they don't please the company.

"Companies are frantic to get out positive results, but not neutral or negative results," he says in an interview. "It's very hard to publish a study that's either neutral or negative on a commercial product."

But some universities and researchers don't agree to those terms. In this instance, Dr. Kahn says, Immune Response had the opportunity to review findings for 30 days, but "no editorial rights."

Drummond Rennie, deputy editor of JAMA, says the journal is going forward with publication "to prevent the bias that comes from reporting only those results favorable to sponsors' products."

Dr. Rennie, who is an adjunct professor with UCSF, says the journal is taking the unusual step of publishing even though Dr. Kahn and colleagues weren't privy to all of the details of their own study during a few months of 1999. This was because Immune Response wouldn't allow the final data from other hospitals to be turned over to them.

Immune Response executives, in an interview Tuesday, said Dr. Kahn and his colleagues at Harvard, Brown and Cornell had no legal right to publish data from other hospitals involved in the study. Ronald B. Moss, the company's vice president of medical affairs, also said the published article "excludes the full presentation" of results showing that Remune did cause enhanced immune-system activity.

He says the company tried to stop publication only "because we think there was important information that was excluded" about such activity by cells in the immune system, called CD4 cells, that help control infections. He says the company still plans to publish such data from the study. Dr. Kahn responds that anything relevant already was in his own article.

By last fall, at a scientific conference in San Francisco, Dr. Kahn and other leading investigators in the study had begun publicly discussing their early views, that they had found no clinical advantage from Remune in avoiding death and the progression of AIDS in patients. Patients in the trial were HIV-infected, but generally were healthy when they began the study in 1996.

The findings were a disappointment. There had been considerable hope among HIV scientists that Dr. Salk's approach of boosting the immune system would help AIDS patients. "We had hoped we would be investigating an important new contribution, and we were disappointed it didn't happen," says Dr. Kahn.

The study was stopped in May 1999 by an independent data-safety monitoring committee, which concluded that there was no realistic chance that the Remune patients would experience any clinical advantage in avoiding death or disease progression if the study continued through September of that year, as planned. Shortly after Dr. Kahn reported similar conclusions, Immune Response declined to allow the last few months of data from other universities to be turned over to him.

"We didn't think anything would come that would change the results," Dr. Kahn says of the researchers' decision to publish with the incomplete data. The JAMA article does describe an increase in the immune system's CD4 cells with Remune, but Dr. Kahn concluded this increase didn't make much difference for most AIDS patients.

"If you give Remune, you get an immunologic response that you can measure," says Dr. Kahn. "Would it delay disease progression and death? No." He says that among some newly infected people, though, "there might still be a role for this treatment in a small way."

The effort to stymie publication actually began early this year. On Jan. 17, Immune Response's medical-affairs vice president, Dr. Moss, wrote to Dr. Kahn that the company itself, and not the researchers, should analyze the study data along with a third-party clinical-research company. Dr. Kahn says he was "flabbergasted."

"To suggest that analysis and manuscript preparation should be removed from the study team," he wrote back to Dr. Moss, "is a break in the agreement and faith we shared and is completely unacceptable. " He wrote that he "could not be a part of the situation you describe" and that he "would hope" that his arguments "would sway you away from this ridiculous plan." In a separate e-mail, Harvard's Stephen Lagakos, co-author of the study, called Dr. Moss's proposal "inappropriate and unacceptable."

Immune Response's president, Dennis J. Carlo, followed with a similar note to Dr. Kahn. "For you to insinuate that you do not trust us and that we will change the data," he wrote, "is something that is very bothersome to me."

Then, a July 26 letter to Dr. Kahn from a San Diego lawyer representing Immune Response contended that research results were the property of the company.

"Data and analysis may be used and published only with IRC's consent," wrote Randall E. Kay of the law firm Gray Cary. "As IRC has already informed you, IRC does not consent to your proposed publication."

Undeterred, Dr. Kahn says he is comfortable with publishing the results. "The patients trusted us to independently and honestly evaluate the data," he says. "The independence of academic research is the overriding theme of our work."

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