U.S. OK's Gleevec for GIST

Novartis developed drug shows ‘unprecedented efficacy’ in rare tumors

The U.S. Food and Drug Administration approved the Novartis drug Gleevec® (imatinib mesylate) for the treatment of patients with c-Kit positive gastrointestinal stromal tumors (GISTs) deemed inoperable and/or having spread.

“Not only have we seen shrinkage in size and quantity of tumors, but patients are feeling better than they have in many months,” said Dr. Charles Blanke, director of gastrointestinal oncology at the Oregon Health & Science University Cancer Institute. Blanke is one of the principal investigators of the initial clinical trials using Gleevec on GIST.

The Feb. 1 approval of Gleevec for GIST came 10 months after the drug was approved in the U.S. for treating chronic myeloid leukemia.

According to Dr. Daniel Vasella, chairman and CEO of Novartis, “Gleevec has already made a major difference in the lives of patients with chronic myeloid leukemia and we’re extremely gratified to now make this drug available to patients with GIST.”

Vasella continued, “Novartis – along with our colleagues in academia and government – continues to study Gleevec and investigate other cancers in which it may help patients – either alone or in combination with other therapies.”

GIST affects some 5,000 to 10,000 Americans a year, striking any of the organs along the length of the gastrointestinal tract or its lining. These tumors are prone to spread to other organs and, once spread, they often are unresponsive to chemotherapy or irradiation, and invariably fatal.

Clinical trials for GIST using Gleevec began in July 2000 at OHSU, Dana-Farber Cancer Institute and Fox Chase Cancer Center.

In clinical trials, more than half of patients with GIST have gone into remission on Gleevec, and more than 90 percent of patients reported major signs of clinical improvement in their conditions.

"This is exciting news, not just because these results validate the theory of targeted therapy, but because these patients have no other options," said Blanke.

For patients with metastatic or unresectable disease, GISTs had represented an incurable malignancy with a median survival of approximately 10 to 12 months. Until now, surgery has been the only effective treatment.

The limited prevalence of GIST has resulted in the FDA designating Gleevec as an orphan drug for this indication.

GLEEVEC and GISTs

The FDA approval for GIST is supported by data from a multinational study conducted in 147 patients with unresectable or metastatic GIST. Patients were randomized to receive either 400 mg or 600 mg of Gleevec daily for up to 24 months.

Gleevec, a signal transduction inhibitor, is one of the first cancer drugs to be developed based on an understanding of how some cancer cells work. Gleevec targets the activity of certain enzymes called tyrosine kinases that play an important role within certain cancer cells. The activity of one of these tyrosine kinases, known as c-kit, is thought to drive the growth and division of most GISTs.

Novartis also has submitted a supplemental filing application for Glivec (as Gleevec is called outside the U.S.) to health authorities in the European Union and in Switzerland for the GIST.

SIDE EFFECTS

Although the majority of patients had adverse events reported at least once during the trial, most events were mild to moderate in severity. In the GIST trial, drug was discontinued for adverse events in six patients (8 percent) in both dose levels studied. In this trial, seven patients (5 percent) were reported to have gastrointestinal bleeds and/or intratumoural bleeds. Gastrointestinal tumor sites may have been the source of GI bleeds.