Cancer drugs proving worth earlier in testing

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By Bill Berkrot and Ransdell Pierson

NEW YORK | Mon Feb 25, 2013 9:07am EST

(Reuters) - Michael Weitz had options. The Californian had undergone chemotherapy, radiotherapy and surgery, but his lung cancer still spread to his bones and the brain.

With time running out, the doctor of the emergency room is entered a phase I study - the first step in human testing of a new drug - of crizotinib. The drug works for about 4 percent of patients with advanced lung cancer with a mutated form of a protein called ALK.

"Once I knew I had this mutation, I knew I had a chance of exciting," said Weitz, now 55, is cancer-free after three years of taking the drug sold by Pfizer now as Xalkori after exceptionally fast development process.

It generally took ten years and $ 1 billion to bring a new treatment on the market. But in the past two years, a handful of drugs against cancer - including Kyprolis Onyx Pharmaceutical Inc. for multiple myeloma, Roche Zelboraf for melanoma and Xalkori Pfizer - were approved in about half the time because of improved genetic testing, phase I trials more definitive and say the need for new therapies.

"We hope to be able to reduce several years time it takes to get final approval and save hundreds of millions of dollars per drug," said Robert Schneider, director of translational research in cancer the New York University Cancer Institute. "We will see this as a radical change over the next five years."

Weitz story is a striking example of how personalized medicine forward 10 years after researchers sequenced the human genome, which can target drugs to specific genetic variations. The new trend is likely to bring more effective treatments for patients desperate rapid increase in the number of annual approvals of drugs and reduce the cost of searching through older data and more reliable. It will also help drug manufacturers to identify ineffective therapies earlier, although it does not necessarily reduce the more expensive drugs.

There are concerns about the approval process faster, but most agree that the benefits of a life-saving drug outweigh the risks. "The accelerated development of new drugs may be a double-edged sword," said Mace Rothenberg, head of Pfizer Oncology. "When you move faster some questions can be answered."

He said those answers can come from tests performed after drug approval, and the FDA often requires post-marketing studies after accelerated approval

Historically, phase I trials does little more than reveal the dose of an experimental drug that could safely be tolerated before major studies determined clinically meaningful benefit. But advances in genetic testing and a better understanding of cancer biology enables researchers to identify patients most likely to benefit from specific treatment of cancer.

"You can see the positive signals much faster, and you can save clinically in patients for whom the drug is not likely to work," said Dr. Michael Davies, Assistant Professor, Department of Melanoma Medical Oncology at MD Anderson Cancer Center in Houston.

Richard Scheller, director of research and early development of the Roche unit Genentech, which produces most of the drugs the cancer society's most sold, said: "you can cut a few years on the testing process clinical principle to your right pivotal Phase I. "

Pharmaceutical companies that have received accelerated approval process has refused to discuss how much money was saved from the industry average for drug development.

NEW FDA "breakthrough" DESIGNATION

Quite impressive with preliminary results, regulators of health are more willing than ever to accept the first test or midstage as sufficient evidence of safety and effectiveness, rather than insisting on a larger, more expensive and time-consuming phase III pivotal studies that have been a standard requirement.

"The drugs are simply better," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, said new drugs targeted against cancer .

With older chemotherapy drugs are highly toxic, he said, "most of the discussions we have had with the agency treated if we should approve the drug or not. With some of these new drugs, the question is how speed we can approve, not whether they should be approved, "said Pazdur.

FDA has developed a new name for breakthrough drugs he sees as a significant improvement over existing therapies. With the appointment - five have been awarded so far with 12 more drugs being studied - the agency works closely with manufacturers to identify more drug approval requirements and work on issues of commercial manufacturing .

DRAMATIC RESPONSE

The key to faster approval of drugs are more closely targeted as researchers better understand the ways of cancer - a series of biochemical steps that fuel the growth of cancer cells. The aim of these treatments is to block protein guilty, or biomarkers, in a way.

"It is much easier for us to offer patients in Phase I of the real possibility of a dramatic intervention," said Paul Sabbatini, an oncologist at Memorial Cancer Center Sloan-Kettering in New York.

Now, far fewer patients need to be tested in order to obtain the final results in early trials, as they are selected only if their tumors contain protein or gene mutations is that the experimental drug. Typically, patients learn more about their medical studies or websites such as ClinicalTrials.gov.

"What we want is many times the phase I data that we see response levels that we have not seen before in patients who have exhausted most therapies to a disease," said FDA Pazdur.

Scheller said that cancer researchers working on 50 different targets that could generate effective treatments in the future.

NYU Schneider, co-founder of the biotechnology company ImClone said in the past perhaps only 3 percent of cancer drugs that began Phase I trials continued to be approved. With new diagnostic tools and targeted drugs, he said, "it is hoped that 10 or even 15 percent of the drugs may be approved for patient populations good over the next five years."

Roche and Pfizer Xalkori Zelboraf Both were developed as well as companion diagnostic tests to identify mutations in specific genes in patients that the drugs were designed to target. They proceeded relatively fast clinical trials.

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

Pfizer Xalkori took a little over four years to develop. If it had been tested in the traditional way in the general population of lung cancer rather than those specific ALK mutation, it would probably have been dismissed as a failure or required further research to try to glean any subgroup of patients have been helped by drugs that cost $ 115,000 per year.

FIND THE FASTEST NON

In the past, large pharmaceutical companies have been reluctant to develop drugs for patient groups are limited, preferring to look for drugs to treat diseases such as high cholesterol and arthritis that could be taken by a broad band of huge population and become profitable.

Pfizer CEO Ian Read has adopted the new personalized approach. Noting the recent advances in genetic understanding, Read said: "We can get clearer results previously This will clearly accelerate our development, as you saw with Xalkori.».

Recent advances may also grant a wish long drug manufacturers - the identification of drugs have failed more quickly.

"It's much better to find out in Phase I of half a billion dollars later in Phase III," Scheller said Genentech.

"If you have a targeted therapy and you do not see the activity of your first 10 or 20 patients who have particular diagnostic marker or biomarker particular you are looking for, forget it, we're through, the project ends," Scheller said.

Even with all the success of recent years, many obstacles remain. Researchers have yet to understand why drugs that act by stimulating the immune system to fight cancer, as Yervoy, Bristol-Myers Squibb, have lasting effects on some patients and not others. And they need to understand why cancer often returns, even when targeted therapies worked.

"We need to know why these drugs stop working sometimes," said Sabbatini Sloan Kettering. "If we understand the cause, we may combine preventive medications, or at the first sign of (disease) progression, understand what is the most logical step as we learn more about the ways."

But as long as the United States did not control drug prices as Europe does, and the FDA does not consider the economy in its approval decisions, faster, cheaper development can not result in lower prices.

"I hope that this would reduce the cost of drugs, but the contract is that the market is going to get," says Schneider.

(Reporting by Bill Ransdell Pierson Berkrot and edited by Jilian Mincer, Claudia Parsons and Edward Tobin)

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