A Triumph in the War Against Cancer

Oncologist Brian Druker developed a new treatment for a deadly cancer, leading to a breakthrough that has transformed medicine

"We're just seeing the start of matching patients with the right drug and seeing rapid improvements," says Dr. Brian Druker. (Robbie McClaran)
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The drug’s cost has been controversial since Day 1. A year’s supply in the United States now runs about $50,000, or around $140 per daily pill. That is twice the original cost, which Vasella had defended as “high” but also “fair,” because the drug gives patients a good quality of life and the company’s revenue underwrites research on other drugs. (Asked about the reasons for the price increase, a Novartis spokeswoman declined to comment.) In any event, a drug that Novartis balked at developing because the market was too small is now a blockbuster. In 2010, Gleevec generated $4.3 billion in worldwide sales—the company’s second-highest-grossing drug. To be sure, Novartis has provided free or discounted medication to low-income patients. In 2010, the company assisted some 5,000 U.S. patients by donating to them $130 million worth of Gleevec and Tasigna, also a Novartis drug.

But patients, doctors and others have long complained about Gleevec’s price. In her 2004 book, The Truth About the Drug Companies, Marcia Angell, former editor of the New England Journal of Medicine, suggested Novartis was “gouging” patients on Gleevec. Recently, physicians have reported that patients stopped taking Gleevec because they could not afford it, despite the company’s assistance program.

Druker, who said his lab has received Novartis research funding but neither he nor OHSU has ever earned Gleevec royalties, deplores the cost. “It should be an affordable price, which would be in the $6,000 to $8,000 a year range,” he told me. “The company would still have plenty of profits.” He went on, “Many cancer drugs are now priced well out of the realm of affordability. As a health care industry, we’re going to have to tackle and deal with that.”

There will be plenty to deal with: it appears Gleevec was not merely a lucky shot. Just the fact that scientists quickly designed new drugs to cope with Gleevec resistance shows they increasingly know what they’re doing, said Sawyers, now at Memorial Sloan-Kettering Cancer Center. He led a group that was the first to explain resistance and was involved in Sprycel’s development. “Why am I so optimistic?” he said. “We know the enemy and we know how to vanquish it.”

Indeed, several enzyme-targeted cancer therapies won FDA approval in Gleevec’s wake, including drugs against particular forms of lung cancer and pancreatic cancer. And researchers say they’re heartened by treatments well along in clinical trials. Some melanoma patients whose disease is caused by a known genetic mutation appear to benefit greatly from an experimental drug called PLX4032. Sawyers is studying a form of prostate cancer spurred by a mutant hormone receptor, and he said clinical tests of a drug (called MDV3100) targeted against it are “exciting.” One pharmaceutical-industry analysis estimates that drug companies are currently developing and testing nearly 300 targeted molecular cancer therapies à la Gleevec.

Arul Chinnaiyan, a research pathologist specializing in cancer at the University of Michigan Medical School, in Ann Arbor, is frank about Gleevec’s influence. “We’re trying to franchise its success,” he said of his attempts to apply the targeted-therapy approach to solid tumors, which are more complex than CML. Each type of solid tumor may be driven by multiple errant enzymes and receptors—protein structures that transmit chemical messages—and the variety of mutations might vary person to person. Chinnaiyan himself has discovered two different mutant gene fusions analogous to BCR-ABL that appear to drive many prostate cancers. “The thought is if we know these are the molecular lesions, we’ll be able to match the drug or combination of drugs appropriately,” Chinnaiyan said.

I got a sense of what he calls “personalized oncology” one day in a brew pub in Ann Arbor. Across the scarred wooden table eating a bacon cheeseburger and sipping ale was Jerry Mayfield, 62, a former Louisiana state trooper. Diagnosed with CML in 1999, Mayfield was told at the time by his hematologist that he had two to three years to live. Mayfield asked if there were experimental drugs to consider. The doctor said no. Mayfield checked the Internet, learned about STI571 and, having taught himself computer programming while manning the night desk at police headquarters in Monroe, created a Web site, newcmldrug.com, to inform other patients. If he’d listened to his hometown doctor, Mayfield said, “without question I would not be here today.”

He still runs his Web site, and these days lives in Bloomington, Illinois. He was in Ann Arbor to see Talpaz, who had collaborated on the initial Gleevec clinical trials in Houston but had moved to the University of Michigan. He has taken care of Mayfield for more than a decade, administering targeted therapies in succession as Mayfield became resistant or could no longer tolerate them: Gleevec, Sprycel, Tasigna, bosutinib and now ponatinib, yet another experimental kinase-blocking CML drug racing through clinical trials.

Mayfield is “a poster boy for CML therapy,” Talpaz told me. “He’s doing extremely well.”

Over the pub’s blaring music Mayfield said of his BCR-ABL gene, “I had the G250E mutation—have the G250E mutation—which is why I became resistant to Gleevec.”


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