Subject: Popular AIDS Treatment Is Illicit Copy Of Hoffman-La Roche's New Drug DDC Date: Published: 7/16/91 (182 lines) Source: Wall Street Journal. Copyright Dow Jones & Co. Inc. Medicine: Popular AIDS Treatment Is Illicit Copy Of Hoffman-La Roche's New Drug DDC ---- By Marilyn Chase Staff Reporter of The Wall Street Journal The AIDS-treatment underground has a new drug of choice. Pirated from Hoffmann-La Roche Inc., the illicit medication is taken by thousands of patients -- often with their doctors' blessing. The drug is an inexpensive knockoff of DDC, a compound that Roche has spent millions of dollars developing over five years. Some 5,000 patients get the real article in limited trials and giveaways while its bid for market approval undergoes Food and Drug Administration review. But over the last year or so, more than twice that number have come to rely on the knockoff. When first tested in 1987, DDC was nobody's panacea, causing widespread nerve damage; at that time, according to a Roche spokesman, it was nearly abandoned as too toxic. Today, at half the dose and often in combination with other drugs, it is better tolerated by thousands of patients. The drug is still far from risk-free, but as a retired San Francisco health-care worker declares, "It's keeping me alive." The DDC phenomenon signals the growing maturation and sophistication of the AIDS-care underground itself: Once famed for importing exotica like Chinese cucumbers, or European antibiotics, it now is copying a patented U. S. pharmaceutical -- and running a calculated risk of regulatory crackdown. The question remains how the Food and Drug Administration will respond to this new challenge to its authority. Commissioner David Kessler declines to be interviewed on the subject. Says a spokesman: "Any promotion, commercialization, or widespread distribution in interstate commerce of an unapproved product is of concern to us." Under the swiftest scenario, it will still be many months before DDC can be approved, as Roche has only recently begun submitting its official new drug application. In the meantime, many people feel crackdown against the underground is remote since suppliers are neither promoting nor profiting from the knockoff. Roche, the U. S. unit of Swiss Roche Holding Ltd., acknowledges a moral and financial quandary. "Yes, they're infringing on a patent. Yes, it's an illegal action from an FDA regulatory standpoint," says spokesman Paul Oestreicher. "But it's a difficult question because people may be getting relief from it." The other touchy issue is obviously price and the incentive to make new AIDS drugs. The underground -- with its shoestring operation and no overhead -- is treating patients for less than a dollar a day. Roche has spent five years developing the drug and is faced with recouping a huge investment -- but ever mindful of the furor ignited when Wellcome PLC set the original price for its pioneering AZT at $8,000 a year. The company insists it is acutely sensitive to the need for moderate price. Ironically, DDC owes its underground success as much to the waning efficacy of AZT as to its own virtues. Its widespread use is evidence that many patients on AZT are falling ill due to drug-induced anemia, or an AIDS relapse brought about by the rise of AZT-resistant viruses. It is DDC's strikingly effective use in combination with AZT, reported at the recent International AIDS Conference in Florence, that has been the source of much recent interest -- and change in physician attitudes. "People are coming in for DDC saying `My doctor sent me,'" says Lewin Usilton, board member of the Healing Alternatives Foundation, a San Francisco buyer's club. "Up to now, I've been convinced what {my patients} took on the underground was doing them no good," says Douglas Richman, a researcher investigating DDC and AZT at the University of California at San Diego. "Now, it's not so clear." "If a drug looks promising, we should be able to include it in the cocktail we give to prolong our patients' lives," says AIDS researcher Jay Lalezari of San Francisco's Mount Zion Hospital. While perhaps no better than AZT as a single agent, he says there is clearly a group of patients benefitting from DDC. Also, it sparks less viral resistance, and its combination with AZT looks promising. Dr. Lalezari finds the conditions that Roche currently imposes on getting DDC to be prohibitive, so he sends patients to the underground. "The peak of the epidemic is just around the corner. These people have been on AZT for a long time. To refuse them DDC would be cruel." And so they go by thousands, to an industrial loft in Manhattan's Chelsea district, or to an office above an herb-and-acupuncture salon in San Francisco. Similar storefronts thrive in Dallas, Los Angeles and Washington, D. C. There, patients can pay about $60 to obtain 400 capsules lasting up to 3 months. Jim Corti, a Southern Californian who is a major link in DDC's underground distribution chain, believes he is doing what he must but hopes government approval will come soon. "The minute the stuff is available commercially, we're out of this," he vows. Derek Hodel, executive director of the PWA (People With AIDS) Health Group in New York, adds, "It's absurd that people must come to an industrial loft in Chelsea to get the medicine they need. We now require a signed statement from patients and physicians to be sure every person is being monitored. We've never had anything that was this serious in terms of toxicity.... We shouldn't be supplying this stuff. I don't think people want to buy drugs in the underground. They {do it} because they're forced to." DDC, like AZT, is a nucleoside analog, a compound that mimics a basic chemical building block of DNA -- the raw material of genes. However, it's much cheaper and easier to make than AZT and is routinely used in a variety of laboratory experiments. Thus, underground members can order it from chemical companies "on the thinnest pretext that it's for research," a pirate says. "It isn't illegal to sell DDC as a chemical. What is illegal is making it in dosage form and giving it to patients." DDC's birth as an underground drug has been aided by a strange alliance between AIDS activists and 1960s psychedelic entrepreneurs. A onetime psychedelic-drug supplier on the West Coast, now battling HIV with his wife, had moved to a bucolic farm to enjoy the last of his life. Then after two years on AZT, his health began to fail him. He lost 30 pounds, becoming too weak to leave his bed or lift a saucer. Then he dusted off his old skills at counterculture chemistry. "All my expertise prepared me for this," says the chemist, who asks anonymity. "You set up a lab. You make the drug. Only now, you make people well. You don't make them high." "I'd like not to end up in jail," he adds. "We've set up a lab producing state-of-theart AIDS drugs. I'm helping myself, but it's a big lifeboat. It costs no more to make a kilogram than it does to make a gram." But DDC's underground production has since outgrown his cottage lab, says this aging hippie. Its distribution has evolved and diversified, and buyers' clubs now are being quietly supplied by a number of domestic and foreign suppliers of pharmaceutical chemicals. Underground DDC is so-called lab grade, which means it isn't subjected to rigorous quality testing. Although the underground does check its DDC for purity, Roche by contrast subjects its drug to 600 separate tests of raw materials and processes. Still, neither government nor Roche officials can so far point to any major problem with impure underground DDC. A larger concern is that DDC has a narrow dosage range and is very easy to underdose or overdose, triggering painful neuropathy in the arms or legs. Patients in 1987 whose nerves were damaged by highdose DDC required narcotics to quell the burning sensation in their extremities. But patients say they are willing to take the risk. "I'd gone through AZT alone since 1987, but I'd gotten anemic," says the retired health-care worker in San Francisco. "Then I took DDI {another drug, made by Bristol-Myers Squibb Co. } and started having gastrointestinal problems. My immune cells started to fall. I tried to get into a DDC study, but was turned down because my lab tests were marginally abnormal. I had to get DDC somehow, so I got it in the underground." Roche has responded to a year of activists' complaints about red tape by slashing paperwork requirements to expand official access to the drug by more than 500 patients a month. But that has not resolved the problem for patients who want to take DDC in tandem with AZT: One of Roche's unbending requirements is that people in the giveaway must have abandoned AZT altogether. "No matter what we do, we're not going to be able to satisfy every patient's need," Mr. Oestreicher says, adding: "We need to remember that the focus is doing studies to get the drug approved." San Francisco physician Marcus Conant, who is caring for 600 patients taking underground DDC, says those patients have other priorities. "It isn't a patient's responsibility to see that {Roche's} research protocol is complete," he says. "A patient's job is to stay alive." [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.]