Some Researchers Are Pleased, Others Indifferent, As RU 486 Moves Toward Ready Availability In U.S.

Some Researchers Are Pleased, Others Indifferent, As RU 486 Moves Toward Ready Availability In U.S. Author: KAREN YOUNG KREEGER, pp.1 Date: August 22,1994 Biomedical researchers working with the antiprogestin RU 486 are expressing varied opinions on the mid-May announcement that the controversial drug will eventually be more readily available in the United States and how that availability may affect their investigations. Some scientists consider the transfer by Roussel Uclaf--the Paris-based manufacturer of RU 486--of U.S. patent rights, free of charge, to the Population Council, a New York-based contraception research group, to be very good news concerning the drug's use in the U.S., both as an abortifacient and in biomedical research. "I believe that when the compound is freely available [in the U.S.], more people will study it," says Leslie Z. Benet, a professor of pharmacy and pharmacological chemistry at the University of California, San Francisco. Researchers such as Benet say that the transfer should overcome some bureaucratic hurdles in obtaining the drug and allow them to conduct research in a less politically charged atmosphere. Others, however, say the move will probably not affect their inquiries into the drug's nonabortifacient uses, as they have experienced few problems in procuring RU 486 or pursuing their studies all along. "The fact that the Population Council holds the patent probably won't affect our research at all," says Steven Grunberg, chief of the hematology and oncology unit at the University of Vermont College of Medicine in Burlington. Some investigators are maintaining a wait-and-see position about the transfer's impact on future research, based on how the Population Council may perceive its interests in supporting and facilitating nonabortifacient RU 486 research. The agreement is the latest chapter in a long international controversy involving the drug's use and availability as an "abortion pill." But biomedical researchers have also been exploring the uses of RU 486 as a potential treatment for such diseases as breast cancer, endometriosis, meningioma, and Cushing's syndrome for the past decade (M.E. Watanabe, The Scientist, Jan. 24, 1994, page 14). In 1991, the Bush administration, allegedly in response to political pressure from conservative and anti-abortion groups, imposed an import alert on the drug, banning it from being brought into the U.S. for personal use as an abortifacient. Serious movement to lift the ban started shortly after Bill Clinton took office as president. In early 1993, officials at the Food and Drug Administration (FDA) along with Secretary of Health and Human Services Donna E. Shalala began negotiations with Roussel and the Population Council, which had been conducting abortifacient research on the drug since the early 1980s. In April 1993, the White House announced that the French company would agree to transfer the rights to RU 486 to the council. The final agreement was signed and went into effect on May 15. Details of the agreement, however, are proprietary information between Roussel Uclaf and the Population Council, according to council officials, and have not been released. Benet says he is "thrilled" by the news. He was chairman of an Institute of Medicine panel that reviewed possible clinical uses of the drug. The panel produced a report in 1993--Clinical Applications of Mifepristone (RU 486) and Other Antiprogestins: Assessing the Science and Recommending a Research Agenda (M.S. Donaldson et al., eds., Washington, D.C., National Academy Press). "It's a hassle to study [RU 486] under its present conditions," says Benet, referring to the existing government approval process for obtaining the drug for research purposes. Because RU 486 has not yet been approved by FDA for any use within the U.S., scientists--with data provided by the patent owner--must submit an investigational new drug (IND) application with FDA to obtain it for research or clinical studies. Once the drug is approved for use as an abortifacient in the U.S.--a more likely prospect now, given the government-brokered transfer--the paperwork and red tape involved in procuring its use in other studies should be greatly reduced, according to many researchers. Some scientists say that lately Roussel has been less than cooperative in supporting some aspects of basic research because the company has been under pressure from its German parent firm--Hoechst AG, located in Berlin--to curtail its involvement with the drug. These scientists and other observers maintain that Hoechst's stance on the matter stems from the religious convictions of its leaders. According to Wayne Bardin, vice president and director of biomedical research at the Population Council, the nonprofit organization plans to secure a manufacturer for the U.S. market within a year. Until then, however, principal investigators proposing new research projects would still have to go to Roussel to get the drug, he says. "Roussel is still providing it for Europe and people who want it in the U.S.," says Bardin. On the other hand, some investigators expect the transfer to have little or no impact on their studies. They say that Roussel has been supportive of their work and the FDA requirements have never been a major impediment to obtaining the drug or conducting their research. Vermont's Grunberg--who is conducting clinical trials of RU 486 in treating nonresectable meningioma--points out that he has had cooperative, long-term relationships with both Roussel and the council, and that his is an "ongoing, FDA-approved project." Although he says "the transition will be seamless" for his lab, Grunberg and other researchers say that it is difficult to predict what the transfer will mean to future projects without knowing which types of nonabortifacient RU 486 studies the council intends to support and involve itself in now that it controls rights to the drug. "I'm not sure how broadly they define their mandate," says Grunberg. "Say, for example, if someone were interested in breast cancer, would they [the Population Council] see that as a cancer-related issue, not in their domain, or would they also define their domain as women's-health issues?" Population Council spokeswoman Sandra Waldman says the council "definitely wants to be involved in developing nonabortifacient uses," but the council is only at the stage of reviewing the literature on the different types of nonabortifacient research. Furthermore, she says, discussions within her group for setting up an entity to deal with this type of research have only just started. She notes that the patent rights to all known medical uses--including nonabortifacient ones--in the U.S. come to the council in the agreement. "That's one of the reasons why we're not even calling it RU 486 here anymore," she says, explaining that the council has decided to refer to RU 486 by its generic name, mifepristone. Waldman says that the council expects to begin clinical trials of RU 486 as an emergency contraceptive this fall. According to FDA and council officials, this means that RU 486 could be available in the U.S. in about two years. However, FDA spokesman Lawrence Bachorik cautions, even if the agency does sanction RU 486 as an abortifacient in the U.S., approval for other uses would not be covered. "The FDA approves a drug and its labeling for a specific purpose," he says. While RU 486 approval as an abortion pill would obviate the need for other projects to submit an IND--with its extensive data requirements and other paperwork--the council or the drug's future manufacturer would still have to file a supplemental new drug application, Bachorik explains. "To us [FDA], it doesn't matter" who manufactures and distributes RU 486, he says. "We want to make sure that there'll be consistent [quality in production of the drug]. We shouldn't have to worry about variation in the product." A major effect of the transfer, scientists agree, is that future basic research using RU 486 is likely to proceed in a less politicized atmosphere than before. They expect the council to choose a company to manufacture the drug that will not be deterred by pressure from anti-abortion groups. Benet predicts that the drug will be produced "by a company that isn't continually worried about the implications of liability from the publicity aspect" of being associated with RU 486. Although many researchers say they have a good working relationship with Roussel, others say that pressure from Roussel's parent company in Germany made the French firm reticent about dealing with RU 486 in general, thus affecting some areas of nonabortifacient research. William Regelson, a professor of medicine at the Medical College of Virginia, part of Virginia Commonwealth University in Richmond, alleges that these pressures stymied Roussel's pursuit of promising breast-cancer research in the late 1980s. "The reason why I look upon this as good news is that we will now have a rational company that is not lying to us [the biomedical research community]," says Regelson. "I think the basic reason why [Roussel] never pursued [the breast cancer research], even though I was given all sorts of excuses, was that they were told by the Hoechst people to lay off." Researchers say the politics surrounding RU 486 as an abortifacient should not be relevant to investigating its other promising uses. John Link, director of the Breast Center and Cancer Institute at Long Beach Memorial Medical Center in California--where clinical trials of RU 486 to treat a form of breast cancer have just started--says he "would be very disappointed if the drug wasn't given a fair trial in breast cancer because the only people who would suffer are the women with the disease. "This aspect of the potential use of the drug really is beyond politics and socioeconomic issues," he adds. And, according to Michael Friedman, associate director of the National Cancer Institute Cancer Therapy Evaluation Program, the institute--which has been modestly funding RU 486 research, including Grunberg's, for several years--is keeping an open mind about new proposals for potential investigations into nonabortifacient uses of the drug. "We are very interested in seeing what drug companies and independent investigators will generate," says Friedman.

Some Researchers Are Pleased, Others Indifferent, As RU 486 Moves Toward Ready Availability In U.S.

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