FDA Approves 'Breakthrough' Leukemia Drug

From the WebMD Archives

May 10, 2001 (Washington) -- In record time, the FDA approved Gleevec for the treatment of a rare but deadly type of leukemia. This pill for chronic myeloid leukemia, or CML, represents a new approach to controlling this disease -- and potentially many other cancers -- because it zeros in on cancer cells, leaving the normal ones alone.

"[Gleevec] appears to change the odds dramatically for patients, and it does so with relatively low occurrence of side effects. ... This oral drug is based on the concept of molecular targeting -- and we believe such targeting is the wave of the future," said Health and Human Services Secretary Tommy Thompson at a news conference here Thursday.

Some of Gleevec's more common side effects include nausea and other abdominal problems.

In CML, white blood cells grow out of control, eventually driving out oxygen-carrying red blood cells. The patient then develops chronic anemia and wastes away. About 4,500 Americans per year develop the condition, which is often untreatable in its later stage.

Currently, CML patients are treated with the medication interferon alfa, but it only works in some patients and can have serious side effects. Bone marrow transplantations can cure CML, but many patients aren't able to find a donor match or deal with the life-threatening side effects. In fact, several patients die from the transplantation itself.

For the last two years, researchers have been studying Gleevec as a way to specifically target and interfere with how CML works at its molecular level. The drug shuts down a key protein responsible for CML's abnormal cell growth.

"This single drug is as interesting and impressive as any we have ever seen throughout our long war on cancer. Yet there are many questions to be answered," says Richard Klausner, MD, director of the National Cancer Institute. Among the issues -- the long-term benefits and side effects of the drug. However, Klausner considers Gleevec "the picture of the future of cancer treatment."


Early studies carried out by Brian Drucker, MD, director of the Oregon Cancer Institute in Portland and one of Gleevac's primary developers, showed that patients who had failed virtually every other therapy responded to this treatment.

"Certainly, I don't think that anything has been seen like this before," Dawn Willis, PhD, scientific program director of the American Cancer Society, tells WebMD.

From that positive result just two years ago, the FDA went on to grant the drug's manufacturer, Novartis, a priority review. Then in just over two months Gleevec was given accelerated approval, a record time for a cancer drug.

Now Gleevec is being heralded as the first example of so-called "rational drug design" aimed at a targeting the genetic malfunction that exists in CML patients. In these individuals, an abnormal chromosome instructs the body to produce too much of a particular protein, which in turn sends out a message to produce more and more white cells.

In effect, Gleevec has been designed to crank down this biological throttle. "So far, we have evidence from over 1,000 patients that Gleevec reduces that level of cancerous bone marrow and blood ... but it's long-range effect on survival remains to be shown," says FDA Acting Principal Deputy Commissioner Bernard Schwetz, DMV, PhD.

The unknowns are not raining on Gleevec's approval.

"This is a great day for cancer research. For the past 30 years, cancer researchers have tried to identify the critical abnormalities that drive the growth in cancers. ... That approach of understanding cancer at its root can be applied in developing drugs to kill the cancers without harming normal cells -- [that] can now be applied to every single cancer," Drucker tells WebMD.

That, he says, could make cancer treatment as manageable as diabetes, high blood pressure, or elevated cholesterol. However, because every cancer is different, there might have to be hundreds or thousands of targeted molecules against specific tumors.

Nonetheless, some evidence suggests that Gleevec's targeted therapy approach may work in a rare intestinal cancer as well as brain or lung cancers, says Willis.

"What is remarkable about this drug -- its specificity for its molecular target -- also means that its potential utility will be limited to those cancers that have those targets," says Klausner.

Over time, cancer cells also may build up resistance to the specific molecules aimed against them.

"Maybe in the future, we'll combine two or three targeted agents," says Drucker.

Meanwhile, Novartis says it wants to make sure that everyone has access to the life-saving drug, regardless of income. "We are going to put in place a comprehensive patient assistance program so low-income CML patients are not denied therapy," says Daniel Vasella, MD, Novartis' president.

Susan Dreger is already one satisfied customer. She started on Gleevac last June after all else failed, and in three months, she experienced a dramatic difference.

"I went from a hard time getting out bed some days to basically picking up my life where I'd left off four years ago when I was diagnosed [with CML]," she says.

New studies on the effectiveness of Gleevac in solid tumors are set to be presented at next week's meeting of the American Society of Clinical Oncology in San Francisco -- another indication of the potential of targeted cancer therapies.