DRAMATIC RESPONSE

Key to faster approval is that drugs are becoming more narrowly targeted as researchers better understand the pathways of cancer - a series of biochemical steps that fuel the growth of cancer cells. The aim of the treatments is to block the culprit proteins, or biomarkers, within a pathway.

“It’s much easier for us to offer patients in Phase I studies the real possibility of a dramatic response,” said Paul Sabbatini, an oncologist at Memorial Sloan-Kettering Cancer Center in New York.

Now far fewer patients need to be tested in order to get definitive results in early trials because they are selected only if their tumors contain proteins or gene mutations that the experimental drug is targeting. Patients typically learn about these studies from their doctors or websites such as ClinicalTrials.gov.

“What we’re looking at many times is Phase I data where we’re seeing levels of response that we haven’t seen before in patients that have exhausted most of the therapies in a disease,” said FDA’s Pazdur.

Scheller estimated that cancer researchers are working on 50 different targets that could yield effective future therapies.

NYU’s Schneider, a co-founder of the biotech company ImClone, said historically perhaps only 3 percent of oncology drugs that began Phase I trials went on to be approved. With new diagnostic tools and targeted drugs, he said, “one would hope that 10 or even 15 percent of drugs might be approved for the right patient populations in the next five years.”

Roche’s Zelboraf and Pfizer’s Xalkori both were developed along with companion diagnostic tests to identify the specific gene mutations in patients that the drugs were designed to target. They proceeded relatively rapidly through clinical trials.

The company said development of Zelboraf, which costs $56,000 for a six-month course of treatment, was the fastest conducted by Genentech and Roche. The clinical trial process took less than five years.

Pfizer’s Xalkori took just over four years to develop. Had it been tested in the traditional manner among the general lung cancer population rather than on those with the specific ALK mutation, it would likely have been dismissed as a failure or required further research to try to glean which subgroup of patients were helped by the drug that costs $115,000 a year.

FINDING FAILURES FASTER

In the past, large pharmaceutical companies were reluctant to develop drugs for limited patient groups, preferring to search for medicines to treat ailments such as High cholesterol and arthritis that could be taken by a large swath of the population and become huge money-makers.

Pfizer Chief Executive Ian Read has embraced the newer personalized approach. Noting recent advances in genetic understanding, Read said: “We can get clearer results earlier. That will clearly speed up our development, as you saw with Xalkori.”

The recent advances may also grant a long-held wish of drugmakers - identifying failed drugs faster.

“It’s much better to find that out in Phase I than half a billion dollars later in Phase III,” Genentech’s Scheller said.

“If you have a targeted therapy and you don’t see activity in your first 10 or 20 patients that have your particular diagnostic marker or particular biomarker that you’re looking for, forget it, we’re through, project ends,” Scheller said.

Even with all the recent successes, many hurdles remain. Researchers have yet to figure out why drugs that work by spurring the immune system to fight cancer, such as Bristol-Myers Squibb’s Yervoy, have long-lasting effects on some patients and not others. And they need to figure out why cancer often comes back even when targeted therapies worked.

“We need to know why these drugs stop working sometimes,” said Sloan Kettering’s Sabbatini. “If we understand the cause, we could preemptively combine drugs, or at the first sign of (disease) progression, understand what is the most logical next step as we learn more about the pathways.”

But as long as the United States does not have price controls for medicines as Europe does, and the FDA does not consider economics in its approval decisions, quicker, less expensive development may not translate into lower prices.

“I would hope it would bring down the cost of drugs, but whatever the market bears is what the market will get,” Schneider said.

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By Bill Berkrot and Ransdell Pierson