FDA OKs New Drug for Cancer
The federal government approved Thursday the first in a new class of designer cancer drugs created to home in on specific molecular targets, leave normal cells alone and avoid the horrific chemotherapy that has characterized most cancer treatments until now.
“This new drug, we believe, is the picture of the future of cancer treatment,” said Dr. Richard Klausner, director of the National Cancer Institute.
The drug represents advances in understanding cancer biology and is a harbinger of a new wave of emerging experimental drugs tailored to the genetic makeup of specific types of tumors.
“It is very hard to describe what a different world this is from just five or six years ago,” Klausner said at a news conference.
The drug, Gleevec, also known as STI571, is a treatment for chronic myelogenous leukemia, or CML, a life-threatening disease in which too many white blood cells are produced.
Gleevec, an oral medication--four pills taken once a day--works by disrupting a cellular signal to the body to produce an enzyme that makes white blood cells proliferate.
The medication causes only minor side effects, among them mild nausea, puffiness around the eyes and muscle cramps.
While the disease is relatively rare--diagnosed in only about 6,000 Americans annually--the drug represents a breakthrough as the first to go after a target that is “not just in a cancer but a target responsible for the cancer,” Klausner said. He said it could play a role--although probably not as dramatic--in as many as 20 different types of cancer.
But researchers cautioned that because the drug has been studied for less than three years in humans they still don’t know the long-term effects of the medication--whether it actually will cure the disease or simply hold it in check.
Still, the results so far have left scientists ebullient.
“I had one patient who was literally planning her funeral, and now she’s out playing with her grandchildren,” said Dr. Brian J. Druker, director of the leukemia center at the Oregon Cancer Institute in Portland, who developed the drug with its manufacturer, the Swiss company Novartis Pharmaceuticals Corp.
“I have another who works 60 hours a week--and that’s a light week for him,” he added.
The Food and Drug Administration licensed STI571 on its “fast-track” approval process after clinical trials showed that the drug restored most patients’ blood counts to normal, and fairly quickly.
Health and Human Services Secretary Tommy G. Thompson, appearing at the news conference with officials from the FDA, Cancer Institute and Novartis, used the occasion to once again tout the value of the government’s support of biomedical research.
He said the development of this drug “underscores the importance of continued investment in research in this country.”
UCLA’s Jonsson Cancer Center was among the sites that conducted the earliest clinical tests of the drug, and one of its researchers, Dr. Owen Witte, was involved in studying the genetic mutation that causes the disease.
This form of leukemia results from a chromosomal abnormality, discovered in CML patients in 1960, dubbed the “Philadelphia” chromosome. It is this chromosome that “turns on” the blood enzyme that causes the white cells to multiply.
CML generally progresses slowly and typically occurs in people who are middle-age or older. It progresses in four stages, the first without any symptoms. As the disease develops, sufferers experience fatigue that won’t go away, a feeling of lethargy, fever, loss of appetite and night sweats.
Conventional treatments have involved chemotherapy and bone marrow transplants.
Druker said the drug has been studied in more than 6,000 patients worldwide since June 1998.
It seems to work best in the earlier stages of the disease, he said.
Druker described a group of 532 patients he studied who started on the drug three years after diagnosis, who had failed to be helped by conventional therapy but had not progressed to the more advanced stages of the disease.
After starting the drug, “close to 90% had their blood counts returned to normal, and in about one-third we can’t detect any traces of leukemia in their bone marrow,” he said in an interview. “Fewer than 2% stopped because of side effects--compare that to chemotherapy.
“You won’t hear doctors use the word ‘miracle’ very often, but when you see results like these in some of these patients, you start to hear that word.”
The drug is less effective, however, when given to those who already have advanced to the late stages of the disease. It helps temporarily, but most eventually relapse, Druker said.
Klausner said that cancer researchers have been devoting their efforts toward identifying a range of new compounds with a similar mode of action.
For example, there are now 68 “targets” identified for breast cancer alone, “for which we now have [drugs] about to go into clinical trials,” he said.
Gleevec is expected to be available within two weeks. While expensive--it will cost as much as $2,400 a month--Novartis officials said the company would establish a program to provide free or low-cost drugs to those who cannot afford it.
While other drug stocks fell Thursday on Wall Street, Novartis shares jumped by $2.65, or nearly 7%, to close at $41.65 on the New York Stock Exchange.
Suzanne Dreger, a Falls Church, Va., woman diagnosed with CML in 1997, was not helped by standard chemotherapy and a bone marrow transplant. She has been taking Gleevec for a year.
Before starting the drug, “I had a long time getting out of bed,” she said. “Now, I’m going back to work and getting back to my life--the way it was four years ago.”
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Targeting Leukemia Cells
The drug Gleevec is based on the principle of molecular targeting, preventing the abnormal growth and production of cancerous cells while leaving normal cells alone. The daily regimen is expected to cost between $2,000 and $2,400 monthly.
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Chronic Myelogenous Leukemia
In chronic myelogenous leukemia (CML), a mutated chromosome within a cell produces a protein, known as Bcr-Abl, that signals the cell to produce an uncontrolled increase of white blood cells.
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How Gleevec Works
Gleevec is designed to block the signals sent out by the abnormal protein, preventing the cell from producing other cancerous cells.
Bcr-Abl sends signals through intracellular pathways that trigger CML.
Sources: Novartis Pharmaceuticals; Current Opinion in Oncology; Associated Press
