A 'Miracle' Drug for Leukemia
Gleevec kills the cancer cells and leaves normal cells alone
THURSDAY, May 10 -- One year ago, Peter Neuert lay tethered to a morphine drip in a hospital in Oakville, Canada, his treatment options exhausted in his seven-year fight against chronic myelogenous leukemia.
"They gave me up at the hospital. They got me ready to die," says Neuert, whose interferon treatments could no longer keep the disease at bay.
But Neuert's wife, Christine, refused to accept the doctors' diagnosis. She started researching other treatment options and learned about clinical trials for a new drug that had shown great initial promise in combating chronic myelogenous leukemia (CML). She then succeeded in getting her husband admitted into Phase II clinical trials for the drug, called Gleevec, which inhibits the enzyme that triggers the excess production of white blood cells.
It was the best gift she could have given her husband.
And today, the U.S. Food and Drug Administration (FDA), following an unusually quick review process for a new drug, approved the use of Gleevec for CML patients.
The "FDA and Novartis, the drug's manufacturer, should be commended for the rapid development and review that will make this product available soon for the leukemia patients who desperately need it," Health and Human Services Secretary Tommy G. Thompson said today.
The drug should be available by the end of this month, the FDA said.
The FDA's "fast-track" decision on Gleevec was based on the drug's stunning success rate with people like Peter Neuert. A week after starting the drug therapy in Portland, Ore., his white blood cell count had plummeted from 110,000 units to within the normal range of 5,000 to 7,000. He abandoned his wheelchair and returned to walking. And he suffered no side effects from the drug, which he took four times a day in pill form. Three months later, his bone marrow showed no evidence of any cancer.
Today, although he still must take the drug, it's as if the 68-year-old general contractor never had the disease, and he's planning an addition to his house.
"It is a real miracle," says Christine Neuert. "If he had stayed in Canada for another couple of weeks, he would have been dead."
The Neuerts aren't the only ones amazed at Gleevec's dramatic results. Members of the medical community are surprised, too.
"Even to a well-informed medical oncologist, [Gleevec] seems like a miracle drug," says Dr. Brian Druker, the Portland-based oncologist who helped develop the drug with Novartis Pharmaceuticals of East Hanover, N.J.
"We were able to target the disease with something specific and non-toxic, which just kills the cancer cells and leaves normal cells alone. The idea is to disable the cancer without disabling the patient."
Dramatic results from the start of testing
Druker and his colleagues got their first glimpse into Gleevec's potential during Phase I trials. All 54 participants with CML saw their white blood cell counts return to normal within four weeks of taking at least 300 milligrams of the drug once a day.
This success rate spurred the FDA to speed up its review process. The agency took the unusual step of giving Novartis permission to conduct Phase II and Phase III trials -- the final stage of the testing process -- concurrently.
The Phase II results, which Novartis submitted to the FDA in February but have yet to be published, "were as good if not better than the results of Phase I," Druker says.
CML is one of four major types of leukemia, a cancer of the blood that causes the overproduction of immature white blood cells in the bone marrow. About 5,000 Americans are stricken with CML each year. Traditional therapies include chemotherapy, radiation, bone-marrow transplants and interferon treatments, all of which can cause side effects, such as nausea.
Ninety-five percent of people diagnosed with CML carry an abnormal chromosome called the Philadelphia chromosome. This chromosome creates an altered gene called BCR-ABL, which ultimately releases an enzyme called tyrosine kinase. It's this enzyme that allows the continued production of "immature" white blood cells, Druker says.
What Druker and his colleagues did was develop a chemical compound -- Gleevec -- that inhibits the activity of the faulty enzyme, thus shutting down the production of immature cells.
'The earlier the better'
Both the Phase I and Phase II trials were restricted to patients who had failed to benefit from conventional CML therapies.
In the Phase I trials, in addition to the dramatic across-the-board drop in white blood cell counts, more than half those taking Gleevec experienced a significant drop in the number of cancer cells in their bone marrow. And seven patients had no signs of CML in their bone marrow at the end of the 18-month study.
The results for the 520 patients in the Phase II trials were equally dramatic: approximately 90 percent experienced a drop in their white blood cell counts to within the normal range after four weeks of treatment. And half showed a reduction or complete disappearance of cancer cells in their bone marrow.
What To Do
To read full coverage of today's FDA approval of Gleevec, read this HealthScout story.
Or read these HealthScout stories on leukemia.