repost from IV fwiw...
....Bristol-Myers Awaits Approval for Drug’s New Cancer Attack
The probable FDA approval of BMY's second-line melanoma drug ipilimumab could bring attention to VICL's A-7, which will hopefully win first-line approval. If so, the two drugs could be used in combination.
Bristol-Myers Awaits Approval for Drug’s New Cancer Attack
By Robert Langreth
March 22 (Bloomberg) -- In 1996, James Allison, a California researcher, uncovered a way in mice to unleash the body’s disease-fighting immune system against cancer. While he was certain the approach could lead to a new kind of treatment against human tumors, he was unable at first to convince drug companies to pursue the idea.
“I hit a wall for a couple of years,” Allison, now at Memorial Sloan-Kettering Cancer Center in New York, said in an interview. “They thought the immune system could never take care of a big mass of tumors.”
Now, a skin-cancer drug based on the concept is close to getting U.S. clearance for its developer, Bristol-Myers Squibb Co. If the Food and Drug Administration approves the drug, called ipilimumab, by its scheduled March 26 deadline, it would become the first marketed medicine proven to extend survival in metastatic melanoma, skin cancer that has spread and is generally lethal.
The drug would also be the first in a new class of immune- boosting medicines able to treat an array of tumors. Instead of directly destroying tumor cells or disrupting their ability to grow like most cancer drugs, these treatments remove molecular brakes that prevent immune system cells from attacking cancer.
Ipilimumab sales in melanoma could reach $925 million by 2017, said Seamus Fernandez, an analyst at Leerink Swann & Co. in Boston “It’s not a stretch to say this would be a multi- billion dollar class” if the drug works in common forms of the disease such as prostate and lung cancer, he said. “Bristol is way ahead of everyone on the immunotherapy front.”
Approval Probable
Tony Butler, an analyst with Barclays Capital, said ipilimumab had an “80 percent to 90 percent probability of approval.” Bristol-Myers shares may decline 5 percent to 8 percent if there is a significant delay in getting the drug cleared, he said in an interview.
The FDA approval would be for patients who have failed other treatments. Yesterday, the company reported a study showing the drug also extended life as an initial therapy.
Bristol-Myers rose 29 cents, or 1.1 percent, to $26.29 at 4:01 p.m. in New York Stock Exchange composite trading. The shares have declined less than 1 percent in the last 12 months.
The American Cancer Society reports that 68,000 Americans develop melanoma and 8,700 die from it each year.
‘Huge’ Potential
“The potential is huge” for ipilimumab-style drugs, Thomas Lynch, director of the Yale Cancer Center in New Haven, Connecticut, said in a telephone interview. Bristol-Myers’s treatment may “pave the way for a whole series of drugs” that prompt the immune system to destroy tumors, he said.
Bristol-Myers is testing ipilimumab in two trials in advanced prostate cancer patients, and plans to begin a final- stage trial in lung cancer later this year. It is testing five other immune-enhancing cancer drugs for multiple myeloma, kidney cancer, and other tumors.
One drug, called anti-PD-1, shrunk or stabilized tumors in 8 of 16 kidney cancer patients, researchers reported at a medical conference earlier this year
“Ipilimumab for us is only the tip of the iceberg,” Renzo Canetta, a Bristol-Myers vice president for research, said in a March 16 speech at a Barclays health-care conference in Miami.
The company declined to make executives available prior to the FDA decision. The agency delayed its initial Dec. 25 decision on the drug until March 26.
Survival Data
In a trial of 676 melanoma patients who had failed other treatments, patients who received ipilimumab lived a median of 10 months, versus 6.4 months for patients in a control group, according to results published in the New England Journal of Medicine in August.
Doctors involved in the test said there are patients living on the drug for years.
“I have treated 250 patients with ipilimumab and at least 25 percent are alive two to five years after starting the therapy,” Anna Pavlick, of the melanoma program at the NYU Langone Medical Center in New York, said in an interview. Normally, they would succumb to the disease within three to six months, she said.
While there are drugs approved in the U.S. for skin cancer that has spread throughout the body, including the chemotherapy agent dacarbazine and interleukin-2, neither has been proven to prolong survival.
Los Angeles resident Susan Reed was 46 when a mole on her back turned red. By the time her doctor removed it in early 2007, the melanoma had spread to her lymph nodes. By June 2008, it metastasized into three inoperable tumors in her left lung.
‘Unbelievably Frightening’
“It was the most devastating thing I have ever encountered,” Reed, who is married with three teenage children, said. “You Google melanoma and every article that comes up is unbelievably frightening. I just couldn’t imagine I would not be there to watch them graduate from high school.”
With few options, Antoni Ribas, an oncologist at University of California, Los Angles, enrolled Reed into a trial of ipilimumab in September 2008. By December, her tumors started to shrink and have continued to get smaller since then, she said.
“It has saved my life,” said Reed, who gets one 90-minute infusion every three months, and says she has not experienced any side effects. “I feel so lucky.”
Ipilimumab is the result of two decades of research into the role of the immune system in combating cancer. It began when immunologist Allison was at University of California, Berkeley, and started looking at a molecule called CTLA-4 that is involved in controlling T-cells the body uses to attack and kill cells infected with viruses and bacteria.
New Theory
Some researchers thought CTLA-4 acted as a gas pedal to turn on the immune system’s T-cells. Allison showed in 1995 that CTLA-4 did the opposite; it worked as a brake, preventing T-cells from rampaging out of control and destroying healthy cells.
Allison said he realized that blocking CTLA-4 might help treat cancer by allowing T-cells to remain active long enough to seek out and destroy a tumor. He made an antibody designed to turn off CTLA-4 and asked a researcher to test it in mice.
“Even in my own lab there were people who thought it wouldn’t work,” Allison said in an interview at his Memorial Sloan-Kettering office. He was amazed by the results, published in Science in March 1996. “The mice that got the antibody were alive; the ones that didn’t were completely dead,” he said.
Little Interest
The University of California patented the concept and Allison tried for two years to get a large biotechnology or drug company interested. “They couldn’t get their arms around the idea,” he said. Rights to the approach ended up with a biotech company called Medarex, which made a human version of the antibody and started testing it in cancer patients in 2000.
Bristol-Myers, which had been studying CTLA-4’s role in various diseases, formed a partnership with Medarex in 2005 and bought the company for $2.4 billion in 2009. Allison, a former consultant for Bristol-Myers, said he would receive a royalty if the drug is approved.
“Innumerable” melanoma drugs have failed in trials, NYU’s Pavlick said. It looked like ipilimumab would suffer the same fate when a 2007 study failed to reach its goal of proving the drug shrank tumors in more than 10 percent of melanoma patients.
One reason for the difficulty is ipilimumab’s novel mechanism, Allison said. While it primes the immune system to attack tumors, it doesn’t trigger the attack directly. It may take months for an immune system response to build up. After starting the therapy, some patients’ tumors continue to grow, and only later start to shrink, according to research reports.
Ipilimumab caused immune-related side effects including itchy skin and colon inflammation, researchers have reported. In the Phase 3 trial, 12 patients died from treatment-related side effects.
To contact the reporter on this story: Robert Langreth in New York at rlangreth@bloomberg.net
To contact the editor responsible for this story: Reg Gale in New York rgale5@bloomberg.net
Last Updated: March 22, 2011 16:08 EDT
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