An experimental drug from Bristol- Myers Squibb Co. helped patients with the deadliest form of skin cancer live longer in a clinical trial.
The drug, ipilimumab, kept about a quarter of patients battling late-stage melanoma alive for two years -- almost twice the proportion associated with standard treatments, said Renzo Canetta, Bristol-Myers’s vice president of oncology clinical research. The company’s study was reported today at the American Society of Clinical Oncology meeting in Chicago.
Malignant melanoma kills some 65,000 people around the world each year, and no drug has been proven to extend survival in a large-scale study once the disease is in an advanced stage. If approved, ipilimumab will be the first melanoma drug to come on the market in more than a decade, and the only one shown to extend survival in the sickest patients in a large-scale study, Canetta said.
“This is such a desperate disease and we have been waiting a long time for something like this,” said Steven O’Day, an author on the study and melanoma doctor at the Angeles Clinic & Research Institute, in West Los Angeles, California. “It doesn’t work in everyone, but about 20 percent to 30 percent have a long-term response for years and not just months or weeks. That is what makes this so different.”
Bristol-Myers, based in New York, said in March that it plans to seek U.S. Food and Drug Administration approval for the medicine this year and aims to get it in the hands of doctors in 2012. Shares of the company dropped 44 cents, or 1.9 percent, to $22.44 in New York Stock Exchange composite trading yesterday. The company has gained 12 percent in the past 12 months.
Melanoma kills most patients within six to eight months after it has metastasized, or spread, from the site of its first appearance on the body -- often in the form of a jagged-shaped black mole.
The number of melanoma diagnoses in the U.S. has been rising, especially among women ages 15 to 39. The annual incidence of the disease in this group rose to 13.9 cases per 100,000 in 2004, from 5.5 per 100,000 in 1973, the National Cancer Institute said in a July 2008 report.
The latest study, funded by Bristol-Myers, followed 676 patients with advanced melanoma who had failed to benefit from two treatments currently available, interleukin-2 or dacarbazine.
The study was divided into three parts. The first group of patients received ipilimumab. The second got an experimental cancer vaccine developed by the National Cancer Institute called gp100, which has been shown to be as effective as standard treatments in extending overall survival. The third group received a combination of the Bristol-Myers drug and gp100.
Patients taking ipilimumab alone lived an average of 10.1 months, according to the study, almost four months longer than those given the gp100 vaccine. Combining the two drugs produced no additional improvement compared with ipilimumab alone. And while 24 percent of patients on the Bristol-Myers drug were still alive two years after entering the trial, only 14 percent of those on gp100 lived that long.
The new drug is central to Bristol-Myers’s plan to bolster its share of the cancer-drug market. The company reported that it had $1.2 billion in cancer-related sales last year. The global cancer market was worth $53 billion, according to IMS Health, a pharmaceutical consulting company based in Norwalk, Connecticut.
Ipilimumab may also help the company’s efforts to fend off competition from generics. During the next six years, Bristol- Myers-branded drugs with more than $11 billion in annual sales will face such a threat, according to data compiled by Bloomberg. The company had revenue last year of $18.8 billion.
If approved, the drug may have $1 billion in annual sales within five years, said Linda Bannister, a health-care analyst at Edward Jones & Co. in Des Peres, Missouri.
Success with ipilimumab will also provide a sign as to whether Bristol-Myers’s strategy of acquiring biotechnology companies is paying off. Last year, Bristol bought ipilimumab’s creator, Medarex Inc., for $2.4 billion. The two companies had previously partnered to develop the treatment.
“This could be a very important drug for them and help them better navigate the patent expirations they face,” Bannister said. “This could be big.”
The Bristol-Myers drug is derived from mice that were genetically altered to create a human version of an antibody, a part of the immune system.
The antibody is designed “to push the accelerator down” on the immune system, enabling a second component, white blood cells called T-cells, to go after the cancer the same way they would a foreign invader such as a virus, O’Day said.
Ipilimumab belongs to a category of new treatments called immunotherapies that mobilize antibodies, T-cells, and other white blood cells to fight tumors. It works by blocking a protein called CTLA-4, which normally keeps the immune system from getting so revved up that it begins to attack healthy tissue.
Along with helping skin-cancer patients, the drug may also be effective against tumors of the lung and prostate gland. If so, the medicine is likely to achieve more than $1 billion in annual sales, said Trevor Polischuk, an analyst with OrbiMed Advisors LLC in New York.
“It is rare that we see such a large group of patients have a curative effect from a cancer therapy,” Polischuk said in a telephone interview. “It is a game changer in oncology both from a treatment perspective, a patient perspective, and from an investor and commercial point of view.”
While ipilimumab is now one of Bristol-Myers’s most promising drugs in development, it could have died in testing two years ago had researchers not noticed what Canetta terms a strange phenomenon among patients who appeared not to be benefiting.
A study released in December 2007 had shown that the drug failed to meet the FDA’s criteria of benefiting at least 10 percent of melanoma patients. Researchers, though, had a hunch the treatment was actually producing a greater benefit than they were detecting. As they continued to study it, they noticed that patients whose tumors were getting larger while they were on the medicine actually showed shrinkage later, when they were taken off the drug. The researchers also found that these patients were living months longer than expected -- and sometimes years longer.
Scientists realized that what appeared to be tumor progression was an inflammatory response from the treatment as the patients’ T-cells attacked the malignancy.
If Bristol-Myers hadn’t categorized these patients as failures and removed them from the trial, the data it reported to the FDA in 2008 would have been different, Canetta said. The company may have been able to prove the benefit was greater than seen in previous studies, and some patients’ lives may have been extended.
Ipilimumab isn’t the first new immunotherapy to be applied to cancer. Dendreon Corp.’s prostate cancer vaccine, Provenge, was cleared by the FDA on April 29. That day, Dendreon’s stock rose as much as 38 percent, and the Nasdaq Biotech Index had its biggest rise in six months.
Also releasing data on immunotherapies at this week’s meeting will be New York-based Pfizer Inc., the world’s biggest drugmaker, which will report results from a study of its brain tumor vaccine. Micromet Inc., a Bethesda, Maryland, biotechnology company, will update doctors about a technology it developed that activates T-cells to attack tumors. German drugmaker Merck KGaA and Oxford BioMedica Plc of the U.K. will show how well their vaccines work against breast and kidney malignancies.