Government To Industry: Join War On Drugs

NIDA offers financial and regulatory incentives, but reluctant pharmaceutical companies are worried about the legal risks WASHINGTON--The federal government wants to persuade the pharmaceutical industry to join its war on illegal drugs. At a two-day conference here this week the two sides will discuss financial and regulatory inducements to drug companies that create medications to fight mental illness to join the battle. Agencies within the Public Health Service are hoping that pharmaceutical companies--many of which produce antidepressants, analgesics, and other chemicals that affect the central nervous system (CNS)--will play a larger role in developing compounds that might one day wean addicts from heroin and cocaine. And they are trying to overcome the industry's traditional reluctance to engage in such investigations by offering them research money, joint development, and the promise of an expedited review of any drugs generated in the lab. Many industry officials remain reluctant to join the war, however. They want assurances from the government that the fight won't cost their firms hundreds of millions of lost investment dollars and untold medical suits. The government-industry conference is part of a fledgling program by the new Medications Development Division at the National Institute of Drug Abuse (NIDA). Established last March, the division is charged to help discover, test, and prepare for market chemical compounds that can be transformed into lifesaving medications for the millions of people dependent on addictive drugs. The conference itself, entitled "Opportunities in Development of Medications for Treating Drug Dependence and Abuse," is a joint effort of NIDA's parent agency, the Alcohol, Drug Abuse, and Mental Health Administration, as well as of the Food and Drug Administration and the Pharmaceutical Manufacturers Association (PMA). Despite these efforts, many drug development experts fear that neither bringing the two sides together to talk nor NIDA's promise of research support and expedited FDA review and approval of new drugs will be enough to ensure progress in the field. They say that the government has failed to address such concerns of industry as the stigma of dealing with this addictive population, the cost of potential product liability suits, and the expected low return on investment. "Right now, I don't think pharmaceutical companies are interested in antiaddictive drugs. There's too much risk," says Duncan Taylor, a senior research fellow at Bristol-Myers Squibb Co. in Wallingford, Conn. "When I tell my colleagues at other companies about the clinical research we do here, they say they wouldn't touch that with a 10-foot pole. Cracking the drug problem will take industry's involvement, but it's not going to happen tomorrow. NIDA and Congress are going to have to do a lot more first to get [industry] convinced." Bristol-Myers Squibb is one of 12 companies that have agreed to collaborate with NIDA in investigating some of the drugs in their storehouse. These drugs are chemical compounds that company scientists either transformed into medications for other CNS uses or set aside after the agents appeared to have no profitable medical use. What Taylor and drug company officials would like to see, in addition to what NIDA is offering, is legislation that would protect companies from some patient lawsuits at the same time it offers them "orphan drug" status in the form of tax incentives and marketing exclusivity. Such legislation is not likely to be passed anytime soon, however. In August, Sen. Joseph Biden (D-Del.) introduced such strong, industry-friendly legislation, but a month later it was replaced by a weaker bill sponsored by Sen. Edward Kennedy (D-Mass.). Kennedy's bill called merely for a study of the difficulties faced by industry in developing medications to fight drug abuse, as well as for $60 million in research support for the program. But the Kennedy bill, too, failed to advance before Congress adjourned last month. Without such legislation, many fear NIDA's efforts may be doomed to failure. "A lot of us have big problems with the lack of legislation," says Michael Williams, acting head of neuroscience at Abbott Laboratories in North Chicago, Ill., and chairman of PMA's drug discovery management subsection, who is scheduled to speak at this week's conference. "We would be quite willing to go ahead with [drug development] on an orphan drug basis. And the liability issue has got to be addressed." Until then, he says, he will remain very cautious. But others echo the sentiments of Biden, who believes that the nation can no longer afford not to have what he labels a "national pharmacotherapy strategy." An estimated 5.5 million people need treatment for addiction to illegal drugs, according to a recent Institute of Medicine report. Yet there are currently only two medications on the market to fight heroine abuse: methadone and naltrexone. No drug exists commercially to treat cocaine addiction. Many scientists, government officials, and members of Congress blame part of the problem on industry's unwillingness to commit its dollars and scientific expertise to the search for better medications to battle drug addiction. "I have gone to many companies and asked for drugs and they say, `Well, that's very interesting.' [But they're not interested.] They see it as a big risk with little payoff," says Yale University psychiatrist Thomas Kosten, who four years ago uncovered the heroin-fighting properties of buprenorphine, a commercial analgesic. "There are hundreds of thousands of drugs that companies have developed, often unsuccessfully, as pain relievers or antidepressants, for instance. They might be nice blocking agents for cocaine, but the companies won't release them because they don't perceive them as having a market." NIDA has developed a multipronged attack to tear down some of those industrial barriers. It features more money for neuroscience research, collaboration with industry on drug development, and an easier path to licensing. The first step is to acquire an array of chemical compounds and discover how they affect the brain. The most promising chemicals will be tested further. "Over the past year we have gone to 30 pharmaceutical firms to get them more involved," says Frank Vocci, director of NIDA's Medications Development Division. "We say, `You've got this drug and we'd like to help you develop it.' We do all the drug screening, animal testing, all the regulatory filing. We do all the things that a drug firm would ordinarily do. By early next year we will be able to take the drug from discovery process through toxicology testing and to dosage form development and then into clinical trials, and then we will hand it back to the pharmaceutical company." While in some cases it may be assuming the role of a pharmaceutical company, NIDA hopes to codevelop medications with other drug firms. These companies would be responsible for filing applications with the FDA and for some research. And, under NIDA's tutelage, they would gradually pick up more of the cost of actual development. Vocci points out that his division can't do all the research on its current annual budget of $40 million. In lieu of more money, NIDA has emphasized increasing communication between the research communities and federal regulatory bodies. Says Abbott's Williams, "Society has a major problem, and the only way to solve it is to share resources. Industry knows how to commercialize products, NIDA has a tremendous research base, and the FDA has the ability to refine the approval base." NIDA intends to do a lot of hand-holding as companies step gingerly through the unknown and dangerous territory of medication development, regulation, and marketing. In preparation for clinical trials, for example, NIDA is working with the FDA to come up with a set of guidelines for industry that spell out everything from picking a study population to testing new drugs safely on multiple-drug abusers to working with HIV-positive patients. These rules should make it easer for industry to understand the details of developing and getting approval for a new antiaddiction drug. The FDA, for its part, is working to expedite the review and approval process. Last spring it established a Pilot Drug Evaluation staff to streamline the regulatory process and cut down on approval time of certain medications, including ones to fight drug addiction. NIDA's Vocci, as well as some industry representatives, say they would also like the FDA to include medications to fight drug abuse in its Orphan Drug Program. This federal program was established to enable drug companies to develop expensive medications to serve a population too small to be profitable. Similar incentives such as tax credits and market exclusivity would be increase a company's commitment to drug abuse medication development, they say. But the FDA says it is not interested. "I wouldn't look to see abuse medications included here anytime soon," says George Stanley, deputy director of the Office of Orphan Products Development. "We're opposed to just having them crammed in here. We look at diseases that affect maybe 10 people, and addiction medications just don't fit into our program. It would be a perversion of the orphan drug act." Industry would also like legislation dealing with product liability, the drug development bogeyman that most scares drug companies. According to a survey last year of its members by PMA, companies involved in drug addiction research are afraid of doing more because of the chance that their drug might cause an adverse reaction with drugs a patient might have taken, leaving them open to suits. "Getting these [orphan drug and liability protection] incentives into legislation is imperative," says Charles Grudzinskas, director of new product management at Lederle Laboratories in Pearl River, N.Y. "Exclusivity and liability are major issues--you can't control a patient who is a walking polypharmacy." At the same time, Grudzinskas says he thinks that a breakthrough in finding a drug to cure cocaine addiction, for example, would trigger an immediate legislative reaction. "I think that before we can expect Congress to act, we have to show some real medical promise," he says. In addition to legislative safeguards, many drug companies would like the government to subsidize the cost of treating this disadvantaged population. "This is not a patient population that is appealing to the pharmaceutical industry," says Louis Harris, a pharmacologist at Virginia Commonwealth University in Richmond. "As customers they have all kinds of health problems due to their lifestyle. [Many drug addicts] are HIV-positive. They are not going to be very profitable to deal with, which means the government will buy their medications for them--at [lower] government rates." Vocci agrees there are many issues of financial reward to be dealt with. "This is not high profit any way you slice it," he says. But he says he hopes that the government, rather than setting a price, will eventually establish a price support system that would assure the industry of a fair return on its investment. Grudzinskas says that the search for antiaddictive drugs could actually turn out to be a bonanza for pharmaceutical firms if it leads to drugs that serve a larger market. Understanding drug addiction, scientists believe, could lead them to the underlying causes of tobacco and alcohol use--perhaps even why people watch so much TV and love chocolate cake, according to one researcher. The understanding may also extend beyond addiction. "Companies get [backing for] research that is going to lead to medications for neurological and mental diseases," says Marvin Snyder, NIDA director of policy and external affairs. "The smart company sees that NIDA is supporting them in some very lucrative research." But NIDA's most important contribution may be psychological rather than financial, says William Martin, a pharmacologist at the University of Kentucky in Lexington and a member of the FDA's drug abuse advisory committee. Drug addiction is often viewed by the public as a sign of moral bankruptcy, he says, and pharmaceutical firms have tried to avoid the stigma associated with working on medications for drug abusers. Having the government play a role in developing medications to treat drug addiction could broaden public understanding of addiction, says Vocci. "Say your mother goes in for an operation and is given an analgesic. She says, `Isn't this the same drug I read about in the paper they're now testing on junkies? I don't want to get hooked.' " says Vocci. "Some companies are terrified of developing their drugs for a second indication." He says he hopes that the involvement of the government in such research may legitimize the idea that addiction is a medical condition that, like diabetes or depression, requires chemical treatment. Already there are signs that industry's stance on the subject may be softening. As the drug pandemic engulfs the U.S., many executives are demanding that their firms become more involved. The PMA board of directors recently proposed establishing a commission on medications for treatment of drug dependence and abuse, expected to be made up of top officials. "The industry people feel a personal and moral obligation to play a role," says Vocci. Grudzinskas, who helped organize the meeting, senses the same shifting of attitude among his industry colleagues: "The pharmaceutical industry has the scientific know-how to develop medications. And I think that ability gives us a moral obligation to develop drugs."

Government To Industry: Join War On Drugs

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