Pfizer Inc.'s just-approved drug Xalkori, the first new medicine in more than six years for deadly lung cancer, proves the value of precisely targeting rare diseases linked to gene variants, cancer specialists and Pfizer executives said Tuesday.

The drug was approved Friday in the U.S. along with a companion diagnostic test for just a small subset of lung cancer patients. It epitomizes drugmakers' new strategy of developing very expensive but effective medicines for relatively few patients to replace the blockbusters for the masses now getting competition from generic drugs.

It's also in the vanguard of long-awaited personalized medicine, in which doctors identify patients with gene changes or variations that fuel their disease and then try to match them with new medicines that specifically target those genes.

"This is a paradigm shift," Dr. Paul A. Bunn Jr., a University of Colorado professor and cancer researcher involved in testing Xalkori, told journalists during a conference call hosted by Pfizer. "It used to be that everybody with cancer was treated the same," with surgery and chemotherapy.

Xalkori, a pill with relatively minor side effects compared to the hair loss and nausea that chemotherapy can cause, was approved for the roughly 4 percent of patients with advanced nonsmall cell lung cancer who have what's called the ALK fusion gene.

When ALK, short for anaplastic lymphoma kinase, and another gene on the same chromosome rearrange their positions and fuse together, the ALK gene stays on constantly, fueling cancer cell growth. Xalkori works by blocking the kinase enzyme, key to that process.

About 6,000 Americans a year develop this cancer, Pfizer said. Those patients, called ALK positive, now can be identified with a $250 molecular diagnostic test developed by Pfizer's partner, Abbott Molecular Oncology. The test was also approved Friday.
"You're going to be sparing individuals side effects (and) the waste of resources, time and drug that really isn't going to help them," Dr. Mark Kris, head of the thoracic oncology service at Memorial Sloan-Kettering Cancer Center in New York, said during the call.

Normally doctors choose among different chemotherpay regimens for each patient, and they may not pick an effective one.

In Pfizer-funded early and midstage studies that led to Xalkori's approval, tumors disappeared, shrank or stopped growing in just over half of patients for nearly two years on average. Research to determine overall survival is ongoing.

By comparison, nonsmall cell lung cancer — about 85 percent of cancer cases — is tough to treat and kills nearly 95 percent of patients within five years. Lung cancer is the top killer among cancers worldwide.

Xalkori, known chemically as crizotinib, costs about $9,600 a month and is taken until it stops fighting tumors, at which point patients likely would be put on older chemo drugs they hadn't taken yet. Pfizer has started a Xalkori patient assistance program with a maximum $100 monthly copayment for insured patients meeting certain financial limits. Insurers are expected to cover the drug for ALK-positive patients.

Jeff Wigbels, an investment bank portflio manager treated in one of the drug studies, said when he started taking it, he couldn't eat because cancer had spread to his throat. Within a week he could eat again and soon scans of his lung and throat no longer showed tumors.

"It was just an amazing experience," he said.

Another patient, Richard Heimler, a former nonprofit executive, said he had one cancerous lung removed seven years ago and repeatedly had new tumors surgically removed from his brain and the other lung, along with chemotherapy. He began taking Xalkori 15 months ago and still takes a pill twice a day.

"My tumors have either disappeared, shrunk or are stable," said Heimler, and he's functioning well again.

Pfizer is currently running two late-stage studies that compare Xalkori to different chemotherapy treatments that have been the standard of care. It's unusual to get approval before completing such large, late-stage studies. Xalkori was approved remarkably quickly, just four years after Japanese researchers reported they had identified the ALK gene variation.

Pfizer is awaiting approval from regulators in the European Union, Switzerland, Japan and Korea, and also is testing crizotinib against other types of cancer.

Pfizer said 3 percent to 5 percent of patients with nonsmall cell lung cancer have the ALK gene fusion. But one research group presented data at a recent cancer conference showing 8 percent of those patients have it.
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Pfizer needs some big sellers because its $10.7 billion-a-year cholesterol fighter, Lipitor, the world's top-selling drug, loses U.S. patent protection on Nov. 30. That starts an unprecedented wave of much-cheaper generic versions of many drugs taken daily by millions.

Geno Germano, head of Pfizer's specialty care and oncology business, said Xalkori's development shows Pfizer's core research operation has bounced back.

After successes including Lipitor, antidepressant Zoloft and impotence pill Viagra in the 1990s, Pfizer's in-house scientists have had a string of high-profile drugs fail in patient testing in recent years. That's forced the company to acquire many new drugs through acquisitions and licensing deals.