The San Francisco Examiner - September 6, 1999
Sarah Yang of the Examiner Staff

"I never saw that kind of gloom on his face before," said Williamson, 52. "I looked at his face and said, "I'm a dead man, aren't I?' "

His physician, Dr. David Reese of UC-San Francisco Cancer Center, confirmed in July that Williamson's kidney cancer, which already had spread to other parts of his body, was growing rapidly. A tumor undetected in tests two months earlier was now the size of a tennis ball. His doctor said he had anywhere from two to eight months to live. If Williamson planned on traveling, Reese advised, he had better do it quickly.

At that point, Williamson began waging a life-and-death battle to gain access to an experimental drug available largely to people in clinical trials. He is not alone in his quest. Many other terminally ill patients in the United States fight similar battles every day. Whether they can - or should - get special access to these drugs is a subject of huge debate.

Williamson has pinned his hopes on anti-VEGF, an experimental drug that has not been approved for market by the U.S. Food and Drug Administration. "I thought, if there's any chance that something might save my life, how will I feel if I'm facing death and I haven't tried to get it," said Williamson, a resident of San Francisco's Mission District. "I just want to know I exhausted all the possibilities for extending my life."

A full-time job

By the time he came to UCSF's Cancer Center in 1998, Williamson's cancer had spread to his lungs, back and near his heart, just one year after his original diagnosis. He had worked various odd jobs around the country, running a wholesale nursery and teaching at a nursery school. Now, fighting his cancer and trying to get anti-VEGF has became his new full-time job.

He had already tried chemotherapy. It hadn't worked; it rarely does for renal cell carcinoma. A newer treatment, interleukin-2, failed as well. It does so in four out of five kidney cancer patients.

The FDA makes room for such last-resort cases under "expanded access" programs, allowing seriously ill and dying patients with no real alternative the chance to take a drug before market approval.

Such programs were broadened in the 1980s in response to demands from AIDS activists for greater and faster access to new medications. Since then, tens of thousands of patients have received access to drugs treating such illnesses as heart disease, AIDS and cancer.

According to some health experts, expanded access programs have become more popular in recent years as more patients use the Internet to find out about new drugs under development.

Ultimately, however, it is the manufacturer - which absorbs the cost of supplying the treatment before market approval - that must weigh the burden of providing expanded access against the desperation of patients clinging to a last chance at life.

In Williamson's case, Genentech in South San Francisco has denied him expanded access to anti-VEGF, an angiogenesis inhibitor that might hinder the growth of cancer tumors by starving their blood supply.

Dr. Sue Hellman, Genentech's chief medical officer and senior vice president, said the company only produces enough of the drug for the patients in the clinical trials.

This is especially true for anti-VEGF. Because it is a monoclonal antibody, a protein that must be produced by living cells, it is extremely difficult - and expensive - to manufacture.

Company careful with trials

Only if enough evidence of safety and possible effectiveness emerges at the end of phase 2 trials would the company consider setting up an expanded access program, said Hellman. Supplying the drug outside controlled trials without evidence that it might help the patient would be premature, she argued, as well as "potentially foolish" and "costly for the company."

She pointed out that if Genentech provided a drug to a single patient, company policy states that a program must be set in place to provide the drug to multiple patients.

"Intellectually, that makes sense," said Bob Erwin, CEO of Biosource Technology in Vacaville. "On the other hand, here we've got a very real person who's dying who might possibly get some benefit from the drug."

Erwin's wife, Marti Nelson, died of breast cancer in November 1994 while trying to gain access to the then-experimental drug Herceptin, also produced by Genentech.

At the time, Genentech had no policy in place to accommodate expanded access demands. It was soon pressured into developing one - with Erwin's input - after protesters handcuffed themselves to cars parked on the company's lawn. Erwin pointed out that expanded access programs, by definition, allow companies to make exceptions based upon compassion.

But Hellman at Genentech said companies risk making arbitrary decisions when they start making exceptions.

"The real fear we have, if we had a single-patient-use protocol, is that the patient who talks the loudest would get the drug," said Hellman. "It's the one who is wealthy or has connections that would benefit, not the more poor or disadvantaged, who may be potentially more needy." Many ask for drugs

Dr. Howard Jaffe, senior vice president of drug development at Gilead Sciences in Foster City, added that it's rarely only one person who wants the drug. "We get these calls every day," he said. Gilead currently has 9,000 patients enrolled in an expanded access program for adefovir dipivoxil, an anti-HIV drug that is on an accelerated approval process at the FDA.

Jaffe said he gets about 20 requests per week for adefovir dipivoxil, which is also going through phase 3 clinical trials for the treatment of chronic hepatitis B virus infection.

At some point, he said, the demand outpaces the company's ability to meet it. "Where do you draw the line?" he asked.

Researchers also worry that providing drugs outside the carefully controlled clinical studies risks clouding up the investigation, and might ultimately slow the drug's approval.

"If you do compassionate-use studies, they're still studies," said Dr. Larry Hirsch, a spokesman for Merck Research Laboratories in New Jersey. "We're still responsible for communicating any experience with the drug to the FDA." Months earlier, Williamson was denied entrance into a controlled clinical trial for anti-VEGF because investigators were concerned his liver was not functioning properly.

Trial researchers have since reconsidered, but Williamson argues that he is now in such an advanced stage of the disease that he cannot bear the trip to Bethesda, Md., where the studies are being conducted.

"Whenever we administer anything to a patient, and if anything untoward happens, we're left trying to determine what was the cause and effect," Hirsch said. "We consume time and resources trying to understand those incidents." So why have an expanded access program at all?

"It's politics and public relations," said Fran Visco, president of the National Breast Cancer Coalition in Washington, D.C. Visco also advised Genentech when the company was developing its expanded access program for Herceptin. "I don't think any biotech company puts an expanded access program into place without pressure."

But Jaffe at Gilead said well-organized expanded access trials can do more than polish a company's relations with the public. "You're learning more about a drug in as near a market setting as possible," he said. "It's like a big field test."

In a financial sense, Jaffe added, the programs also help develop a group of patients who might continue using the drug after it is marketed. Patients unrealistic

Richard Klein, HIV / AIDS program coordinator at the FDA's Office of Special Health Issues in Maryland, said his biggest concern about expanded access is that people go into experimental trials with unrealistic expectations. "People often assume if something is coming down the pipe, it's better," he said. "But it's still research, and that means it has a lot of risks."

These patients, said Klein, are often left "grasping pieces of wood from a sinking ship. But we have to put the wood there."

Jeff Getty, a prominent HIV / AIDS patient and activist, said it is important for many terminally ill patients to fight for new therapies, regardless of whether they work.

"You have to look at the mental status of somebody who is fighting for his life," said Getty. "It's more about keeping your sanity than about your survival."

In 1996, Getty made national headlines when he underwent a baboon bone marrow transplant, a procedure that prompted ethical and medical debates about cross-species transplantation.

Getty is working with another drug company to get an experimental drug still in phase 2 trials. "I've been playing this game for 12 years, and I've managed to survive," he said.

As for Williamson, he understands the drug might do little or nothing to stop his kidney cancer from advancing.

But he said that companies holding so much potential influence over a person's life should still be bound by a moral imperative, when asked, to help those with no other choice.

"If a company is going to make millions of dollars selling a product to the public," he said, "shouldn't they be at least slightly beholden to that public, before (the drug) is approved by the FDA and while they have to pay for the drug?

"The reality of my situation is that this anti-VEGF, I probably won't get it," he said. "And even if I did get it, it probably wouldn't save my life. The most I could hope for is a stabilization of my disease."

Williamson continues, on principle, to fight for compassionate access to anti-VEGF, but every once in a while he actually shakes his head and laughs at his situation.

"You can't get too serious about it," he said. "I've had a rich and exciting life. I've done just about everything I wanted to do. I have no regrets." cancer, relaxes on his bed as he talks of his dream of traveling the world.

The San Francisco resident is one of many terminally ill U.S. patients attempting to obtain access to experimental drugs in an effort to halt the progression of their disease
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