Subject: End of Du Pont Venture Spurs Questions Date: Published: 9/1/88 143 lines Source: Wall Street Journal. Copyright Dow Jones & Co. Inc. End of Du Pont Venture Spurs Questions --- Move Clouds Trials Of AIDS Drug Ampligen ---- By Michael Waldholz Staff Reporter of The Wall Street Journal A controversy is flaring over Du Pont Co. 's mysterious announcement that it is dropping its support of an experimental drug for AIDS. Without explanation, Du Pont announced Aug. 18 that it would pull out of a joint venture with HEM Research Inc. to develop the drug, Ampligen, as a treatment for acquired immune deficiency syndrome. The big chemical maker said that it would continue to supply the drug, which is extremely expensive to make, and that it would financially support studies already in progress, but that it wouldn't back any further studies after the venture is officially dissolved in mid-November. Since then, officials of Du Pont, based in Wilmington, Del., have steadfastly refused to elaborate on the announcement. They also have refused to comment on reports that Ampligen is failing to show any significant effect against AIDS or that trials of the drug have been compromised because patients secretly began taking other AIDS therapies. Du Pont's partners at HEM Research -- a small, Philadelphia biotechnology concern that developed Ampligen -- were flabbergasted by Du Pont's decision. "I know of no scientific or business reason for Du Pont to end the joint venture," says Ian Brick, president and chief executive officer of closely held HEM. Mr. Brick says Du Pont's abrupt move prior to the completion of a major clinical study "is bizarre." He and several academic researchers studying Ampligen say it continues to show promise as an AIDS drug. "I have got to believe that it was purely a business decision made by Du Pont," says Mathilde Krim, a biologist and founding chairwoman of American Foundation for AIDS Research, a nonprofit group that has pressed for rapid testing of experimental AIDS drugs. Ms. Krim, a longtime campaigner for research into Ampligen, complains that Du Pont's failure to explain its action "puts a shadow over the drug it does not deserve. I am worried that Du Pont's action will make it very hard for HEM to keep and recruit test subjects or attract future financial backers." Du Pont's tie with HEM wasn't unusual for the drug industry. In the race to find an AIDS cure, for example, a number of large companies are establishing presences by bankrolling small outfits in the costly procedure of clinically testing a drug. A look at some of the reasons for Du Pont's pullout, based on a number of interviews, offers a glimpse into the particular complexities involved in developing AIDS treatments. Indeed, while AIDS activists and others attack the federal bureaucracy for dragging its feet on AIDS research, the Ampligen affair illustrates that other factors also have hindered the effort. When researchers at Hahnemann University in Philadelphia presented the preliminary results of a pilot study of 25 patients last December, Ampligen had already aroused intense interest. The results suggested that the drug stabilized the immune system of patients with AIDS-related complex, or ARC, a condition that often precedes AIDS. The patients had an increase in the number of their T-4 cells, key agents in the immune system; a decrease in the amount of AIDS virus in their blood; and no serious side effects from the drug. While Ampligen didn't seem effective in patients who already had developed AIDS, and some AIDS researchers cautioned that even its positive effects in ARC patients involved too small a sample of patients to allow for a proper analysis, the report spurred great excitement. Some AIDS activists called on the Food and Drug Administration to allow widespread use of Ampligen, especially because it seemed safe. "I'm not exaggerating when I say that around then, about every other patient I was treating for AIDS asked about Ampligen," says Susan Krown, an AIDS researcher and physician at Memorial Sloan-Kettering Cancer Center in New York. Within weeks of the report's release, Du Pont announced it had formed a joint venture with HEM to fund and oversee clinical trials of the drug, including an important 300-patient test comparing the drug with a placebo in patients with pre-AIDS conditions. Earlier in 1987, Du Pont had agreed to acquire a small stake in HEM in exchange for rights to manufacture and market Ampligen. While financial details of the joint venture agreement haven't been released, it was undertsood that Du Pont would produce the Ampligen for the study and provide cash needed to keep the trial going. Weeks before the Aug. 18 announcement, top Du Pont officials are believed to have begun questioning the investment. According to several sources, Du Pont had conducted its own analysis of the pilot study at Hahnemann -- which had grown to 40 patients -- and its review produced a less positive picture of the drug's ability to boost the immune system. Also, the sources say, Du Pont officials were concerned when they took an interim look at progress of the 300-patient study and saw that many patients had developed AIDS. Moreover, the 300-patient study was being complicated by two factors that haunt all AIDS drug trials. In order to get into the study, some patients hid the fact that they had suffered from certain illnesses. Those maladies would have tipped off researchers to the fact that the patients were too sick to be in the study. Thus, many test subjects were progressing to AIDS much more quickly than expected. Also, some patients, worried about their declining health, began taking the AIDS drug AZT. Both situations meant that the study would need to enroll perhaps four times the original number of patients and that it would take much longer to complete than planned, sharply increasing the study's costs. Du Pont's decision to dissolve its Ampligen venture may well have been sealed following a meeting it called in early August in which the test results were presented to a group of AIDS research experts. One of the AIDS researchers at the meeting says the data presented was "equivocal." "I didn't see that there was evidence yet that the drug in humans was better than any number of other unproven agents," says Daniel Hoth, head of the National Allergy and Infectious Disease's AIDS drug program. He says that he thinks "more research should have been done before they undertook such a large {300-patient} comparative study," but that he was "very surprised by Du Pont's action" to end the venture. Some industry executives believe Du Pont's unwillingness to state its opinion of Ampligen is an effort to avert a lawsuit from HEM. But the company's silence is upsetting patients in the drug trials. "There is enough uncertainty with AIDS without this going on, too," says one ARC patient who has been in the pilot study for more than a year. "If they'd tell me what's going on, I could decide whether I ought to drop out of the Ampligen study and pursue other experimental treatments." [This article is made available here by Dow Jones Co. for the personal and non-commercial use of callers to this bbs, in the hope that it will be of some help to those who are suffering from the disease and others who are seeking to help them.]