National AIDS Task Force Expected To Accelerate Drug Development

Bench scientists will play a major role in an ambitious effort to streamline the campaign against HIV The soon-to-be-appointed National Task Force on AIDS Drug Development may have a strong, positive impact on the research and development of antiviral therapies to counter HIV infection, say industry and academic scientists, government officials organizing the task force, and members of the AIDS-affected community. Key to the task force's effectiveness, however, will be the personnel selected by Secretary of Health and Human Services, Donna Shalala, probably in early February, to serve on it, these sources say. "People's views run the gamut from cynical to optimistic," says activist Derek Hodel with the AIDS Action Council in Washington, D.C. "Those of us who are optimistic hope that the task force will be effective at its charter in identifying barriers to research and to drug development, of which there are many. If it's well-appointed and well- staffed, it's quite likely that it could have a major impact." If the task force is able to begin dismantling these development barriers, laboratory scientists pursuing AIDS therapies and vaccines--in industry and academia--may find themselves part of a more coordinated approach, overall, to conquering the disease, sources say. This new approach may include better access to screening and trial information, more standardization of data from those sources, and improved laboratory services from the government. The formation of the 15-member task force was announced at a November 30 news conference by Shalala, with HHS assistant secretary of health Philip R. Lee named as head. Underscoring the importance placed on the new group, Shalala was accompanied at the announcement by Harold Varmus, National Institutes of Health director; David Kessler, Food and Drug Administration commissioner; Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases; P. Roy Vagelos, chairman and chief executive officer of Merck & Co. Inc., Whitehorse Station, N.J.; Moises Agosto, National Minority AIDS Council; and White House AIDS policy coordinator Kristine Gebbie. A 30-day period of public nominations followed in which about 200 individuals were suggested for membership on the panel. During January, an internal planning group of about 30 representatives from various government groups responsible for combating AIDS worked to select a task force with balanced representation from the constituent groups: industry, academia, government, and AIDS patient advocates. The planning group's suggestions were to be forwarded to Shalala for her approval early this month. At least one researcher does not believe that the new National Task Force on AIDS Drug Development will be able to speed the development of cures for the disease. And he does not believe that it will be bureaucratic sloth that confounds the task force. Nor will it be because HIV, the virus thought to be responsible for AIDS, changes and mutates beyond the reach of scientists, he predicts. The task force will fail, says Peter Duesberg, a professor of molecular and cell biology at the University of California, Berkeley, because HIV is not the cause of AIDS. "Would it help to pour in ten more billions of dollars to send a man to the moon if there is no moon?" asks Duesberg. "Money and the task force and more input help if you know the enemy. But--if you ask me--we have not identified the cause of AIDS, and you can't get good public health on the basis of bad science." Very few other investigators agree with Duesberg's notion that the scientific world has come too soon to consensus on the hypothesis that HIV is the cause of AIDS. Even fewer accept his alternative explanation for AIDS, that recreational drug use is responsible. But Duesberg insists that HIV cannot be the cause of AIDS, because it is not present in a high enough proportion of the T cells of people with AIDS to account for the disease. "A virus that doesn't infect more than one in a thousand T cells can hardly be responsible for the loss of those cells," he says. "Viruses are obligatory intracellular parasites. They can't work from a distance. They can't sit on a couch and send a message to a distant cell: `Please die.' A virus is a piece of chemistry that can only kill or affect a cell by entering it. If it's not in the cell, nothing's going to happen. Now, there are not enough HIV viruses around [in the body] to explain AIDS....So, HIV is a totally inadequate explanation for one of the hallmarks of AIDS, which is immunodeficiency." Duesberg says he has paid dearly for his out-of-the- mainstream views on AIDS. It is his opinion that the lack of peer approval for his ideas cost him his National Institutes of Health funding. He also feels that his experimental science has been effectively stifled as a result, because he cannot adequately support a laboratory and students financially. "I've sacrificed my whole damned career for this thing now," he says, "and I still think I'm trying to contribute something to--not hurt--American science." The reason AIDS researchers everywhere have been frustrated over 12 years of intense efforts, Duesberg says, is that the hypothesis that HIV causes AIDS is simply wrong. "No matter how hard you hit the virus," Duesberg says, "if it is not responsible for AIDS, no matter how big and how smart the task force, you won't get anywhere." The task force's specific goals will be defined by the group itself at initial meetings, expected in March. But, broadly, the group's charter is clear. "They're being asked to look at the entire spectrum of AIDS drug development, everything from product screening through clinical trial issues, and even regulatory issues," says Randolph F. Wykoff, associate commissioner for AIDS and special health issues at FDA. Wykoff's office has been responsible for coordinating the nominations and staffing process. "They're going to be asked a fairly simple question," Wykoff adds. "Are there any roadblocks that currently exist that are prohibiting or delaying the rapid development of drugs for HIV and HIV-related disease? Or, are there creative new alternatives that should be tried, given that we're now 12 years into it and don't have curative agents?" Many in the AIDS-affected community are supportive of the new task force in concept, but are reserving judgment until the panel is named and begins work, according to Greg Gonsalves, a member of Treatment Action Group (TAG), an AIDS activist organization in New York. Gonsalves is a coauthor of the report, AIDS Research at the NIH: A Critical Review (Amsterdam, the Netherlands, TAG, 1992), that found the AIDS research effort at NIH to be uncoordinated and lacking in leadership. Sen. Edward Kennedy (D-Mass.) and others cited the report's analysis in moving to strengthen the Office of AIDS Research at NIH under the NIH Revitalization Act of 1993. "Everything is not expedited in AIDS research," says Gonsalves. "Maybe this committee can help speed things up and improve some weaknesses in the clinical development effort. But we're waiting to see who's going to be on it, because that's going to drive the task force." At the news conference, Shalala noted that government funding for AIDS research continues to climb, with NIH, for example, receiving $1.3 billion this year for research on AIDS, a 21 percent increase over last year's figure. And only a few days after Shalala's announcement, the Pharmaceutical Manufacturers Association in Washington, D.C., released a survey of its members show- ing more than 100 AIDS-related drugs in development; other estimates suggest as many as 500 such drugs may be in testing in industry. "But the sad fact remains that not a single New Drug Application for an antiretroviral drug is currently before the FDA," Shalala said. An antiretroviral drug, in this context, would be one that successfully attacks HIV. There are only three antiviral drugs on the market today to fight HIV infection: AZT from Burroughs Wellcome Co., Research Triangle Park, N.C.; ddI from Bristol-Myers Squibb Co., New York; and ddC from Hoffmann-La Roche Inc., Nutley, N.J. Each of the three is limited in its effectiveness, partly because of HIV's ability to quickly mutate and acquire drug resistance. "Unfortunately, none of the drugs we have today are curative," Lee said at the conference. Since the news conference, on January 5, Bristol-Myers Squibb Co. announced that it had filed a New Drug Application for an antiviral, anti-AIDS compound called d4T, although it, too, is not a curative therapy. "The three drugs currently approved are all nucleoside antiretrovirals, in that they go after reverse transcriptase, which is the enzyme the virus needs to grow," says Susan Yarin, a company spokeswoman. "d4T is also among that class of drugs." The effort being expended nationally and internationally to find a cure for AIDS is enormous, scientists and government officials agree. If the task force can raise the level of information sharing among those involved in AIDS drug discovery and development, AIDS investigators say, it will serve an important purpose. "Certainly, to facilitate communication among investigators as well as among drug companies would be a big help," says Flossie Wong-Staal, Florence Riford Professor in AIDS Research at the University of California, San Diego. "At the same time, if the FDA can simplify the regulatory process, that would make it easier for a potential therapy to reach the clinic." Wong-Staal, whose laboratory is working to develop both therapies and vaccines for HIV infection, adds: "Drug discovery is a challenge, but translating a discovery to the clinic is an even greater challenge." At Shalala's November 30 news conference, only one person was named to the task force: the man who will head the group, Philip Lee. But most observers will be surprised if Edward Scolnick, the president of Merck & Co.'s Merck Sharp & Dohme Research Laboratories, is not also selected. Scolnick spearheaded an unprecedented cooperative effort among 15 of the largest pharmaceutical companies that is, at least partly, the model for the national task force. Scolnick currently heads the group, formed last April and called the Inter-Company Collaboration for AIDS Drug Development. Under the terms of the collaboration, company scientists have met to share information on compounds under development, at least through the early human effectiveness phases of investigation. Companies are also sharing drug supplies and discussing ways they might standardize the testing of isolates and compounds, so that data can more easily be compared. The national task force may be able to offer similar kinds of help to AIDS researchers, says FDA's Wykoff. "I don't want to sound like I know where the task force is going, because I don't," Wykoff says. "But there might be a way that a researcher in the field can find out everything that's been done with a given product through a variety of screens. There might also be some sort of standardization process, where every potential candidate [drug] would go through a pattern of four or five different screens. Perhaps folks in the field would be able to send in samples to the government for that screening. The idea is that there could be a greater reservoir of information available to the researchers and a greater amount of government service available to them." One hopeful area of cooperation for the industry collaboration centers on combination therapies, that is, using simultaneously administered batteries of drugs under development--presumably at different companies--to circumvent HIV's adap- tive capabilities. The industry task force effort, as a whole, is expected to streamline AIDS drug development and lessen redundant efforts. "If you have all the scientists in one room who are involved with the different compounds," says Gail Levinson, a spokeswoman for Hoffmann-La Roche, "it can have an impact on whether you continue to develop [a given compound], develop it in conjunction with another compound, or, perhaps, make a decision to terminate it completely." At least one Inter-Company Collaboration member has recently decided to leave AIDS drug discovery research to others in the future. Indianapolis-based Eli Lilly & Co. announced last month that, while it would continue research in some AIDS syndrome areas, such as the bacterial and fungal infections that afflict people with AIDS, it would no longer pursue new AIDS antivirals. Lilly currently has one promising antiviral compound, LY300046, that it hopes to continue developing with the help of a collaborator, according to spokesman Fritz Frommeyer. Partly for this reason, the firm intends to remain part of the industry collaboration group for the foreseeable future. Following its meetings, the industry group has met with members of the AIDS-affected community to share information with them, as well, according to Jennifer Mc-Millan, a spokeswoman for Glaxo Inc., Research Triangle Park, N.C. The national task force, while including industry representatives, is not expected to duplicate the efforts of the Inter-Company Collaboration. "Industry, by itself, has somewhat different priorities than the whole task force will have," says David Barry, senior vice president of research, development, and medical affairs at Burroughs Wellcome Co. "The industry task force is extremely focused on drugs that have gone through Phase II and the issues surrounding combination drug therapy trials. The national task force, which will have government people and activists, as well as industrial people, will be looking at a broader range of issues, including drugs to treat opportunistic infections, regulatory hurdles, preclinical requirements, and the like." Data concerning new drug development are often among the most closely guarded information at pharmaceutical companies. While there are no plans to share results at the discovery research level, the fact that the companies have agreed to share valuable screening and development data is a reflection, perhaps, of the frustration level among AIDS researchers. "We entered AIDS research in 1986," says John Doorley, a spokesman for Merck. "We're the world's largest drug company, and this is the largest discovery research project we have ever had. "Last year, we spent $1.2 billion on research, and AIDS was our biggest research project. And, like the rest of the world, we have failed repeatedly."

National AIDS Task Force Expected To Accelerate Drug Development

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