Topic of Cancer

South San Francisco biotech firm Genentech just says no to women battling breast cancer

Judith Fried, 31, speaks with a certain exhausted urgency. The cancer has taken a large toll.

Her diagnosis — a malignant lump in her breast — came three years ago, when she lived in New York City. The lumpectomy, the chemo, the radiation didn't make a dent: Her cancer quickly spread to her lungs, spleen, and liver. But there was one thing that did seem to help: HER-2/neu monoclonal antibody, an experimental drug currently being developed by Genentech, the biotech company in South San Francisco.

As reported in the Aug. 16 issue of SF Weekly (“As They Lay Dying”), a number of Bay Area women have been struggling, unsuccessfully, to convince Genentech to give access to HER-2/neu, which is not yet approved by the Food and Drug Administration (FDA). Fried counted herself as lucky: She was able to receive the high-tech substance when she gained entry to a Phase 2 clinical trial in San Francisco. It was, as it so often is, a difficult feat — a feat made even more trying when a hospital lab lost the tumor sample she was required to give. The lab didn't find it until the clinical trial was already full. Fried complained vociferously.

“And Genentech agreed to let me in,” Fried says, from the Castro Street apartment where she now lives with her sister. The results were worth the aggravation.

When Fried started taking HER-2/neu — a genetically engineered substance that helps control certain malignancies — an estimated 10 to 25 percent of her liver was filled with tumors. By trial's end, Fried says, “the cancer had shrunk to the point where it was not visible by CAT scan.”

Another benefit: HER-2/neu didn't induce the sickness, hair loss, and body-wracking side effects of chemotherapy.

Which is why Fried and other women — two of whom died while waiting for the drug — are demanding that Genentech dispense the HER-2/neu on an individual, compassionate-use basis, something that a number of drug companies do for AIDS patients (a step taken only after years of lobbying by AIDS activists).

Fried and her sister, Elise, have called Genentech and told officials they understand the risks involved. They've agreed not to file suit should the drug do harm or fail to help. Fried's doctor has requested the drug from Genentech on her behalf (request denied). And Fried, meanwhile, was buoyed by an announcement from the company last month — following nearly a year of protests by breast cancer activists from ACT UP/Golden Gate and other groups — that it would indeed start dispensing the drug on an experimental basis, in what's called an “expanded access program.”

What the company didn't mention was its target date: early 1996.
“They've told me nothing can be done,” Fried says. “They've told me they'll put my name on a list and get back to me in December.”

Elise Fried has tried to argue that her sister, at the very least, deserves a maintenance dose — particularly if one considers the language of the Phase 2 trial she attended at Mount Zion Hospital. “Patients having a minor, partial, or complete response at Day 70” — which Judith Fried had — “may be continued on maintenance therapy,” the description reads.

Genentech officials and researchers, both Frieds say, have interpreted the language to their own benefit. Though Judith Fried's liver tumors subsided while on HER-2/neu, her other malignancies kept growing, which researchers interpreted as “disease progression.” People with disease progression are not eligible for maintenance therapy, officials told Fried. And they kicked her out.

Since stopping HER-2/neu, her liver has swelled with even more tumors than before she started.

Such news enrages activists like Marilyn McGregor, chief of the HER-2/neu negotiating team for ACT UP/Golden Gate.

“It makes sense that it's going to take time for Genentech to set up their expanded access program,” McGregor says. “But we think there can be individual compassionate access before the large-scale program is set up, for people who are nearly at death's door.”

To that effect, McGregor wrote Genentech in late June, asking — as she had before — that the company offer “compassionate drug access on an individual case-by-case basis.”

Genentech will be meeting this week with McGregor and other breast cancer activists to discuss this and other matters, McGregor says.

In the meantime, Fried is relying on chemotherapy. A bone tumor, which had stopped growing during the HER-2/neu study, has started to flare. Her liver cancer, which subsided on HER-2/neu, has now accelerated to the point where it disqualifies her from other experimental studies, she says.

“I'm not sure I'll make it to December,” Fried says. Genentech is aware of this, she adds. “They don't care. They don't care.”

Genentech also denied compassionate use of HER-2/neu to Marti Nelson, 40, a physician, who died Nov. 9, 1994. (As with Fried, one of Nelson's most critical lab reports somehow fell through the cracks: It took three months, says Nelson's husband, for Genentech to notify Nelson that her cancer might respond to HER-2/neu. She died the next day.) Evelyn Moulton, 51, a teacher and Ph.D. psychologist, died Aug. 2. Both women had been dedicated activists who sought better treatment options for all those in need.

Why didn't Genentech comply with their requests?
It simply would cost too much to supply individuals with the pricey, bioengineered substance, Genentech officials say. And besides, they can't give anything out until they have designed a program and won FDA approval for it.

But other drug companies do provide individual allotments, says Gracia Buffleben, a breast cancer activist who herself is struggling with the disease. All it takes is a doctor's approval, a drug company's nod, and permission from the FDA — all of which can happen in a matter of weeks, once things get moving, she says. “I've just received a drug under compassionate use and all my physician had to do was write a little summary about whether I had any side effects.

“Genentech's explanation is just so inhumane,” says Buffleben.
Genentech, meanwhile, is entering Phase 3 in its HER-2/neu drug trials, which establish the safety and effectiveness of pharmaceuticals, and are required for FDA approval.

“There's only so much of the drug to go around,” says Genentech spokesperson Kathleen Rinehart. “So it becomes a very difficult decision. Because there are limited amounts of the drug, and by giving it to people individually, we could deplete the supply,” Rinehart says. “We're trying to come up with something that helps the most people in the long run.

“I think the bottom line is that we made the decision to conduct and provide an expanded access protocol, and we are working to make that come about.”

Long-term prospects for HER-2/neu appear, so far, to be good. It is only useful in women, typically young women, who have a very aggressive form of breast cancer in which the surfaces of certain cells overproduce the HER-2/neu protein, sparking uncontrolled cell growth and tumors. But HER-2/neu therapy, unlike chemotherapy and radiation, appears not to poison healthy cells along with cancer cells — it stops the secretion of the offending protein only. About 20 to 30 percent of women with breast cancer have the type of tumor that might respond to this treatment.

Yet until HER-2/neu is approved, getting it, Fried fears, will continue to be an experience that diminishes power, that strips down people already struggling with reduced strength.

If you're too sick, you can't qualify to get a drug. If you're not sick enough, you don't qualify either. If your tumor grows by 25 percent, and the drug company says 25 percent is grounds for being expelled from a trial, then out you go. And it is the drug company, in the end, that decides what is 25 percent, and what is 24.9 percent. The difference, perhaps, between life and death.

“I want people to know,” Fried says. “Because most people don't find out until it may be too late.

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