Underground AIDS Drug Test Being Staged

Frustrated by the lengthy federal drug approval process, nine doctors in San Francisco, New York and Los Angeles are conducting underground clinical trials of a highly touted AIDS drug from China in hopes of speedily determining its safety and effectiveness.

The controversial experiment is not sanctioned by the U.S. Food and Drug Administration, and some in the medical community are questioning the ethics and methodology of the experiment. One of the 42 patients who have been injected with the drug, known as Compound Q, since May 24 died Saturday at San Francisco’s Mt. Zion Hospital.

The drug can cause extreme side effects, and it was unclear whether Compound Q played a role in the patient’s death. Doctors conducting the experiment say they have seen laboratory and clinical improvements in some patients.

Doctors sometimes administer unauthorized drugs for cancer and other life-threatening illnesses, “but I have never seen a more sophisticated and well-organized underground network than with (the Compound Q experiment),” said one Los Angeles researcher who is not participating in the drug trials.

“We would have liked to have done this study formally, and with the approval of the FDA,” said Dr. Paul Rothman of Los Angeles, one of the participating doctors. “But one person dies from AIDS every 30 minutes. We felt that as long as we proceeded on a rigorous scientific basis, we would be on very strong ground.”

“We are trying to get an answer on this drug as quickly as possible,” added Martin Delaney, co-director of Project Inform, a San Francisco-based information clearing house and advocacy group for AIDS patients that organized the network of doctors.

The FDA declined to comment Monday on the experiment.

Dr. Alan Levin of San Francisco contended that the experiment is a “treatment program” and, therefore, legal under federal regulations that permit physicians to use imported but unapproved medications on desperately ill patients.

But Dr. James Kahn, a UC San Francisco assistant professor of medicine who is conducting FDA-sanctioned trials of a synthetic version of the drug at San Francisco General Hospital, questioned Levin’s interpretation. Kahn said he feared that the death of a patient in the underground trial could prompt the FDA to slow down or stop his own study.

Death Unrelated

“Let me stress that (the patient died) in an unsanctioned trial that is completely unrelated to ours,” Kahn said.

“I also worry that the unauthorized experiment lacks proper checks and balances, such as an institutional review board to protect the rights of experimental subjects,” Kahn added. “What is the agenda here: To find a better AIDS drug, or to show up the FDA?”

Delaney had hoped to withhold news of the trials until he had definitive results to report but went public after the NBC “Nightly News” reported on the trials Monday evening.

The official version of the drug, manufactured by Genelabs Inc. of Redwood City and being used in the San Francisco General experiments, is known as GLQ-223. It is a synthesized version of a Chinese drug made from the root tubers of a cucumber plant known as Trichosanthes kirilowii .

The drug has stirred considerable excitement among AIDS researchers--and near-hysteria among AIDS patients--since its developer, Michael McGrath, released results of laboratory experiments earlier this year that showed that GLQ-223 selectively killed HIV-infected macrophage cells.

HIV, or the human immunodeficiency virus, is believed to be the cause of AIDS. The fact that the drug attacks infected macrophages is thought to be especially significant because the cells serve as a reservoir for the virus.

Delaney organized the trials because he believed that academic researchers were being too conservative. Compound Q, or Trichosanthin as it is sometimes called, has been used by doctors in China to induce abortions and for cancer treatments since the Third Century.

Delaney dispatched couriers to China, where the drug is manufactured in a plant 80 miles outside Shanghai. He said Chinese officials were bribed to make thousands of doses available.

“We got a big shipment out the day before the Tien An Men Square massacre,” he said.

Meanwhile, he and Levin recruited doctors and patients for the study. To prevent possible lawsuits if something went wrong, each patient was videotaped giving his informed consent to be part of the study.

The drug is thought to have such potential that the American Foundation for AIDS Research, which has close ties to academic researchers, sent observers to monitor and audit the underground trials, according to several of the doctors involved. A foundation spokesman declined immediate comment.

Rothman, based on his observations of 15 patients in Los Angeles, said the Chinese drug “appears to be the most effective AIDS medication available or on the horizon.”

Kahn refused to discuss the results of San Francisco General’s official trial, which began last month. Known as phase one toxicity trials, the trial is designed to determine the maximum tolerable dose of the drug in human beings.

Viral Activity

Delaney and several of the doctors conducting the unauthorized trials said early results were promising. Many of the patients’ level of P-24 antigen--key indicator of viral activity--had gone down, and some patients had shown clinical improvements.

“But I want to stress that this is not herbal tea,” Delaney said. “This is radical chemotherapy. Some of the patients have had a very rough ride.”

Patients with AIDS-related dementia have suffered especially bad side effects, most likely because the drug was killing infected brain cells, Delaney said.

Delaney still hopes to present data about the drug’s efficacy from his experiment to the FDA.

“Even if the drug doesn’t work, we will have shown that it is possible to accelerate things,” he said.

“So much progress in drug development is being held back by the system’s unwillingness to take risks,” he added.

He acknowledged that the death of one subject, who like the others was in an advanced stage of AIDS, will make an already controversial experiment even more so. Levin said the patient died from suffocation after vomiting in his sleep.

“He did not die from Q,” Delaney added.

But Kahn, conducting the official trial at San Francisco General, said such a conclusion was premature.

“Maybe the drug so incapacitated the patient that the vomiting caused him to die,” he said. “Who knows? I don’t know. They don’t know. I don’t believe the study was done carefully enough that anyone will know.”

AIDS DRUGS OK’D--Two drugs received approval for treatment of AIDS. Page 4