By Robert Langreth - May 31, 2012 .. Bristol-Myers Squibb Co. (BMY) is making progress developing a new drug to assist the body's immune system in its ability to find and attack cancer cells. The drug may prove especially effective fighting lung cancer. Bristol-Myers, the farthest along of at least five companies pushing ahead with this cancer-targeting approach, received U.S. approval in March 2011 on a drug that attacks melanoma by unleashing the body's T-cells to fend off the cancer. Now, early tests on a Bristol-Myers therapy affecting a different immune-system lever is showing promise against advanced lung tumors, tied to more than a quarter of U.S. cancer deaths yearly, as well as other deadly malignancies. The Bristol-Myers Squibb offices in Lawrence, New Jersey. In an initial trial of 240 patients, the Bristol-Myers drug, known as BMS-936558 , shrunk tumors in 24 of 95 melanoma patients, 10 of 33 people with kidney cancer and 13 of 75 of those with advanced lung cancer, according to preliminary information on the data, gathered in the first phase of tests usually needed for regulatory approval. Photographer: Christopher Barth/Bloomberg . "This could be a breakthrough for lung cancer," said Julie Brahmer, an oncologist at the Johns Hopkins Kimmel Cancer Center in Baltimore. In an initial trial of 240 patients, the Bristol-Myers drug, known as BMS-936558, shrunk tumors in 24 of 95 melanoma patients, 10 of 33 people with kidney cancer and 13 of 75 of those with advanced lung cancer, according to preliminary information on the data, gathered in the first phase of tests usually needed for regulatory approval. If the result holds up in further trials, the therapy may become a "backbone" for future combination treatments that attack cancer by weakening it with chemotherapy while simultaneously unleashing an immune system assault, said Seamus Fernandez, an analyst at Leerink Swann & Co. in Boston. In this case, Bristol-Myers's drug may reap more than $4 billion a year in sales, he said.
Final-Stage Trials "It is the early stage of a whole new field of cancer therapy," Fernandez said in a telephone interview. Bristol-Myers rose less than 1 percent to $33.48 at the close in New York. The company's shares have gained 18 percent in the past 12 months. The drugmaker, based in New York, is competing with Merck & Co. (MRK) of Whitehouse Station, New Jersey, London-based GlaxoSmithKline Plc (GSK), Roche Holding AG, of Basel, Switzerland, and Teva Pharmaceutical Industries Ltd. (TEVA) in Petach Tikva, Israel, to test the idea in patients. Updated data on Bristol's experimental compound will be reviewed at the American Society of Clinical Oncology meeting that starts June 1 in Chicago. The preliminary results are promising enough that Bristol- Myers plans to move directly into final-stage human trials in lung cancer, melanoma, and kidney cancer, skipping the second of three phases of drug development. The lung and kidney trials are slated to start this year, and the melanoma trial by early 2013, Sarah Koenig, a company spokeswoman, said.
'A Turning Point' "After many years of negative studies, the idea of reactivating the immune system against cancer seems to be paying off," Roy Herbst, chief of medical oncology at the Yale Cancer Center in New Haven, Connecticut, said by telephone. "It is a turning point in the way we approach this disease." It will take years of testing before researchers know for sure whether the drugs, led by Bristol-Myers's product, represents a real breakthrough or yet another hoped-for cancer cure that fizzles in large trials. Still, oncologists are particularly enthusiastic about the potential of Bristol-Myers's drug to treat lung cancer, which hits 226,000 Americans each year, killing about 160,000 of them, according to the American Cancer Society. Patients with advanced lung cancer who fail to respond to chemotherapy often die within six to nine months. The potential ability to produce "prolonged responses" that aren't seen with other drugs makes it "the most exciting class of drugs right now," said Scott Gettinger, a Yale Cancer Center lung cancer specialist who is testing the drug. He wouldn't comment on the updated data until it is presented at the cancer meeting.
Patient Response David Gobin, a 62-year-old retired police officer from Manchester, Maryland, who is one of the first patients to undergo the treatment, is convinced the medicine is working for him. Gobin's lung cancer jumped into his liver and the space around his lung despite his treatment with chemotherapy and radiation, he said. Within two months after starting on the Bristol-Myers therapy in February 2011, the tumors began to shrink, and they remain dormant today, he said in a telephone interview. Gobin said he is breathing better, has gained back 20 pounds he had lost and next month plans to play golf again for the first time in years. "I've beaten the odds," Gobin said. "This is a miracle drug for me."
Cellular Switch Over the last decade, researchers have homed in on a cellular switch, referred to as PD-1, that may be triggered by cancer cells to help them evade destruction by the immune system. Brahmer of Johns Hopkins refers to it as an 'invisibility cloak.'' Bristol-Myers's drug is designed to work by binding to the switch, blocking the ability of tumors to access it. The medicine produced remission lasting a year or longer in a small minority of patients who had failed on other therapies, according to meeting abstracts released May 16. Company executives won't comment further in advance of the cancer meeting, Koenig said. At the oncology meeting, researchers are expected to present updated data from the trial examining how long the remissions from the anti-PD-1 drug last. Cancer researchers have worked on therapies to trigger the immune system against cancer for decades, with limited success until recently. The field achieved a breakthrough in March 2011 with the approval of Bristol-Myers's Yervoy, the first drug proven to extend the lives of advanced melanoma patients. Yervoy, designed to blunt a different immune system off switch, generated $514 million in sales in its first 12 months.
Many Cancer Types The PD-1 switch is linked to many tumors types and may extend the success of cancer immune therapy. A key issue will be whether the PD-1 drugs can stimulate the body against tumors without causing dangerous autoimmune reactions. One lung cancer patient in the Bristol-Myers drug trial died from lung toxicity linked to the medicine, according to the meeting abstracts. While PD-1 was discovered two decades ago by Kyoto University researcher Tasuku Honjo, it took years for researchers to appreciate its role in cancer. In one 2002 study, cancer researcher Lieping Chen, now at Yale University, showed that numerous types of human tumors, including cancers of the lungs, ovaries, colon, and melanoma, have high levels of a protein that can trigger the PD-1 switch on immune cells. This and similar data from other scientists indicated tumors use PD-1 as a mechanism to evade the immune system, Chen said.
Surprising Result "It was a major surprise," Chen said in a telephone interview. The current thinking is that there is a war between the immune system and cancer, said Gordon Freeman, a molecular immunologist at Dana-Farber Cancer Institute in Boston. While the body successfully wipes out many tumors at the earliest stages years before they produce symptoms, eventually "some of them escape and grow to become terrible things," he said. Manipulating PD-1 is one of the ways the tumors may do this, he said. One of the first companies to focus on PD-1 was Princeton, New Jersey-based Medarex Inc., which started developing a PD-1 antibody in 2005 with Ono Pharmaceutical Co. of Japan, and was acquired by Bristol-Myers in 2009 for $2.4 billion. Ono has rights to the PD-1 antibody drug in Japan, Korea, and Taiwan.
'Mop Up' Cancer Among other competitors, Merck is presenting data at the meeting showing that its PD-1-blocking drug helped shrink or stabilize tumors in four of nine patients in an early trial. The immune approach "ultimately may result in cures for metastatic cancers that we have not been able to cure in the past," said Gary Gilliland, a Merck senior vice president. It may be especially effective when used after chemotherapy to "mop up" remaining tumor cells and prevent the cancer from recurring, he said. Roche (ROG) is in the earliest stages of human testing on a drug that works by a slightly different approach and may be more effective, said Stuart Lutzker, a vice president at Roche's Genentech unit. Instead of binding to immune cells, the Roche drug acts inside tumors to block their ability to shut down immune cells, he said. Though Bristol-Myers has about a two-year lead on its competitors, it's still too early to know which approach will prove most effective, said Leerink Swann's Fernandez.
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