By PETER LOFTUS
CHICAGO—Novartis AG's Gleevec is one of the closest things to a miracle drug to come out of the battle against cancer in recent years. But new research suggests two newer drugs are even more effective for the form of leukemia whose treatment Gleevec has transformed.
In separate studies published Saturday, Bristol-Myers Squibb Co.'s Sprycel and Novartis's Tasigna each were superior to Gleevec in treating people with newly diagnosed chronic myeloid leukemia. The two newer drugs are currently approved to treat patients whose disease persisted after trying Gleevec.
The new studies could help widen the patient populations for both Sprycel and Tasigna if doctors begin choosing them over Gleevec for newly diagnosed patients.
Switzerland-based Novartis has already applied for regulatory approval to market Tasigna as a first-line treatment, and New York-based Bristol said it is in the process of doing so for Sprycel. Some doctors may not wait for formal regulatory approval to try the newer drugs as first-line treatments.
But some doctors might still stick with Gleevec until Tasigna and Sprycel can demonstrate a long-term survival advantage over Gleevec. Also, Gleevec could be viewed as a more cost-effective option when the drug loses patent protection and cheaper generic versions become available in coming years.
"We don't know yet about long-term survival," said Sonali Smith, oncologist at the University of Chicago Medical Center. "We probably won't have that data for quite some time."
Gleevec was introduced in 2001 and quickly became the standard of care for people newly diagnosed with CML, a cancer of the blood, based on its ability to induce remission and significantly improve survival versus older drugs, with relatively low toxic effects.
Studies have shown at least 80% of Gleevec users were still alive eight to 10 years after beginning therapy, much higher than the historical survival rate of less than 20% for CML patients before Gleevec. Gleevec had world-wide sales of $3.9 billion last year.
But not all patients improve on Gleevec, and newer drugs were initially aimed at helping these patients. Sprycel was introduced in 2006 and had 2009 sales of $421 million. Tasigna, which came out in 2007, had 2009 sales of $212 million.
Both Sprycel and Tasigna are more potent in going after a certain molecular target than Gleevec, so researchers studied whether they would work better than Gleevec in the first-line setting. Results were released at the annual scientific meeting of the American Society of Clinical Oncology and published simultaneously by the New England Journal of Medicine on Saturday.
In the Bristol-funded Sprycel study of 519 newly diagnosed CML patients, some 77% of Sprycel users had "complete cytogenetic" responses after 12 months of follow-up, versus 66% in the Gleevec users. This is one measure of remission, when the disease is virtually undetectable in bone marrow.
In a separate, 846-patient study supported by Novartis, some 80% of Tasigna users had complete cytogenetic responses, versus 65% of Gleevec users.
Both studies, while not designed identically, also looked at another measure of remission, known as major molecular response. This was achieved in about 44% of Tasigna users after 12 months, versus 22% for Gleevec. In comparison, the corresponding rates in the Bristol study were 46% for Sprycel and 28% for Gleevec.
Novartis also released data showing Tasigna continued to be superior to Gleevec after 18 months of follow-up.
Hagop Kantarjian, an oncologist at University of Texas M.D. Anderson Cancer Center in Houston who served as an investigator in both trials, said Sprycel and Tasigna were superior to Gleevec at inducing remissions, but some doctors may want to wait for three- to five-year follow-up data before substituting these drugs for Gleevec.
There were various side-effects associated with each drug in the studies, such as skin problems and headaches for Tasigna and accumulation of fluid in the chest for Sprycel. But Charles Sawyers, a cancer specialist at the Memorial Sloan-Kettering Cancer Center in New York, wrote in an editorial in the NEJM that all three drugs have "outstanding safety profiles."
Dr. Sawyers raised the question of whether the new data would render Gleevec "forever enshrined in the history of oncology but no longer useful." But he said Gleevec may get new life when it goes generic: "With rising pressure to balance cost and efficacy, patients and payers may be forced to select the cheapest among three excellent treatment options."
Novartis has patent protection for Gleevec in the U.S. until 2015.
Dr. Kantarjian said Sprycel and Tasigna would have to show significant improvement in survival to justify their prices versus generic Gleevec in first-line CML.
Pfizer Inc. is developing a similar CML drug, bosutinib, that would compete against the others if it reaches the market.