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CRT's Lawsuit: An Eight Year Battle With the FDA

The Campaign for Responsible Transplantation (CRT), a New York-based coalition of 90 international public interest groups, believes that cross-species transplants or xenotransplants should be banned because of the risk of infecting patients and the general public with viruses from genetically altered pigs - biotechnology companies' source animals of choice for cells, tissues, and organs.

On November 27, 2000, CRT retained the Washington, DC public interest law firm of Meyer & Glitzenstein, and filed a historic lawsuit against the US Food and Drug Administration (FDA). The lawsuit sought all FDA-generated records related to side-effects, including infections, and deaths in human xenotransplantation trials.

Published journal articles have revealed that, since 1992, at least 16 patients have died during or after xenotransplant trials. Eight patients died in 1997 after having their blood "filtered" through pig livers at Cedars Sinai Medical Center in Los Angeles. A year later, another patient died at the Mayo Clinic in Rochester, Minnesota after undergoing a similar procedure. In all these cases, the patients' deaths were attributed to previous medical conditions and not to the xenotransplants themselves. But those deaths have been kept out of the public eye and CRT wanted to scrutinize the records.

A brief filed by CRT on January 15, 2002, revealed that by December 1997, one xeno trial sponsor, Diacrin, had documented 232 adverse events in connection with clinical testing of its NeuroCell-PD product alone, which used pig cells to treat Parkinson's Disease. In April 2000, the FDA halted a Diacrin stroke trial because two patients suffered side-effects after having pig cells injected into their brains.

The precise number of adverse events in xenotransplant trials is unknown because the FDA keeps that information secret. In fact, the FDA has spent almost six years fighting the release of documents to CRT, costing an immeasurable waste of time, energy and resources for all involved. And many have indeed been involved.

In March 2001, six biotechnology companies intervened in the litigation between CRT and the FDA, to limit or prevent disclosure of documents to CRT. They were: Novartis Pharmacauticals Corporation, Diacrin Inc., Genzyme Corporation, Diacrin/Genzyme LLC, Circe Biomedical, Inc., and Nextran, Inc.. All of these companies are directly involved in xenotransplantation research, most with xeno-related investigational new drug applications (INDs) pending, or having been completed through the FDA.

In its lawsuit, CRT explained that the xeno-related records it was requesting should not be exempt from disclosure since trial sponsors have themselves divulged details about their human experiments to the media and the public through press releases, the Internet and presentations at FDA-sponsored public meetings. Although the FDA claimed that thousands of records could lawfully be withheld from CRT as "trade secret" and/or "confidential commercial information," the Court disagreed. On September 4, 2002, United States District Court for the District of Columbia Judge Ricardo M. Urbina, ruled that the FDA failed to prove that it could withhold approximately 27,000 records concerning xenotransplantation clinical trials from CRT because the agency did not describe the documents in sufficient detail, or prove that they could lawfully be withheld.

In early summer 2003, the FDA released a sampling of documents to CRT related to "IND G" - one of 18 such xeno INDs. Hundreds of pages were redacted and/or contained meaningless meeting or e-mail transcripts. But some documents contained exactly what CRT was looking for - information about adverse events that occurred during the course of "IND G" or IND 5680 - a Diacrin trial of its NeuroCell-PD product.

Here is a sampling of what we found in numbered documents that were released to us in this FOIA case in 2003:

#473 - "This amendment reports a basal cell carcinoma that was surgically removed from one of the patients. In the Phase II study there have been several neoplasms reported. . . In view of the transplant cells containing PERV sequences, an increased prevalence of neoplasms needs to be carefully evaluated as a possibility." ["No Action Indicated" box checked on this form.]

#501 - "This amendment reports a potential serious adverse event related to the product. The patient was markedly confused post-op and required a prolonged hospitalization."

#488 - "This amendment contains information on a patient who had neurologic symptoms after implantation that were possibly related to the product."

#696 - Death of patient 2. [No further information on this death].

#367 - Basal cell carcinoma removed from patient ["No Action Indicated" box checked.]

#368 - Malignant melanoma removed from patient, thought possibly due to medications ["No Action Indicated" box checked.]

#14 and #592 - Post-op stress-related encephalopathy, freezing and hallucinations, other drug side-effects.

#676 - "The location of subdural [hematoma] suggests a relationship to the transplant procedure itself. . ."

#269 - Chronic hematoma, headache, slurred speech

#159 - (Brain) hematoma, body soreness

#584 - Patient with exacerbation of Parkinson's symptoms, attributed to medications

#583 - "Freezing and hallucinations in a subject, deemed. . . related to medications"

#574 and #591 - Subject 103-K-7 hospitalized and evaluated for stroke; patient admitted for stroke and coronary bypass surgery.

#9 - Reviewer, James Kaiser, says that "the number of SAEs [serious adverse events] was too high for IND 5680.

#400 - Pig that might have tested positive for viruses was used as a source for neural tissue in Diacrin's Parkinson's trial.

#353 - Memo from Phil Noguchi to Amy Patterson etc.: He says: "I pointed out that the public health concerns with xenotransplantation are considerably different than those faced by GTR [gene therapy]."

These documents are concerning to us, particularly the high rates of different tumors in the patients. We were alarmed that the tumors were apparently not biopsied, and that there were so many "No Action Indicated" boxes checked on the Adverse Event Reporting sheets, despite what appeared to be serious adverse events, including cancers. This is especially worrisome in light of the fact that mammalian C-type retroviruses, like the porcine endogenous retrovirus (PERV), cause a wide array of diseases including malignancies and immunodeficiencies.

In April 2005, the FDA began releasing more documents pertaining to the remaining 17 xeno INDs. On May 31, 2005, the Court issued an Order setting a "Document Production Schedule" for the remaining documents at issue. CRT is continuing to review documents as they come in. CRT is the only organization in the US to have sued a government agency to obtain information about the risks of xenotransplantation. We consider this long legal battle, and the release of these documents by the FDA, a victory for all activists concerned about the dangers of biotechnology and xenotransplantation in particular.

The FDA, which has approved over a dozen clinical xenotransplant trials, has admitted that xenotransplantation is dangerous. Leading virologists and FDA officials have acknowledged that the technology could transmit known and unknown animal viruses to patients, their families, health care workers, and the public at large, possibly triggering an AIDS-like pandemic. Despite these concerns, hundreds of patients have been treated with xenotransplant products since the early 1990s - many before the issuance of any formal guidelines. Companies and government health officials are promoting xenotransplantation as a panacea for the human organ and tissue shortage despite mounting concerns about risk and the availability of safer options. Given a growing catalogue of new killer pig viruses, bird flus, AIDS, and more recently bioterrorism, shouldn't we be putting our scarce health care research dollars to better use?

Alix Fano, MA
Director
Campaign for Responsible Transplantation

April 7, 2006