The fight against the deadliest form of skin cancer received a significant boost with the approval Friday of a treatment that promises for the first time to prolong the lives of melanoma patients.
The therapy, called ipilimumab, also gives fresh validation to efforts to attack cancer by enlisting the body's own immune system.
Cancer typically has been treated either by cutting out a tumor, or destroying it with radiation or powerful agents like chemotherapy. By the time tumors spread throughout the body, as in metastatic melanoma, those traditional approaches don't work well. So researchers have sought for decades to deploy the body's immune system in the fight.
But early efforts generated weak responses, melanoma specialists say. Ipilimumab, approved by the Food and Drug Administration for metastatic disease, heralds a new line of these so-called immunotherapies that promise greater effectiveness, though it comes with limitations.
Melanoma afflicted 68,130 Americans last year and killed an estimated 8,700 people, according to the National Cancer Institute. If caught early enough, the disease can be cured. But once it spreads, it has proved difficult for the few existing treatments to stop in all but a small fraction of patients.
In a 676-person study submitted to the FDA, almost half of those treated with ipilimumab—either alone or on top of another treatment—were alive a year later, compared with 25% of patients treated only with the existing treatment. After two years, more than 20% of ipilimumab patients were alive, compared with 14% in the control group.
"Melanoma is a disease in which we are making some real progress," said Steven Rosenberg, chief of surgery at the National Cancer Institute.
The progress comes with a substantial price tag. Bristol-Myers Squibb Co., which plans to sell the therapy under the brand name Yervoy, says it will charge $120,000 for the four infusions given over three months that will be the standard course of treatment.
Bristol-Myers Chief Executive Lamberto Andreotti defended the high price, saying Yervoy has been shown to significantly extend survival. "There is a real value that is delivered from this drug," he said.
The infusion, which is delivered intravenously, can cause side effects such severe diarrhea and even lead to death, though doctors say the side effects can be avoided with careful monitoring and treatment with drugs like steroids. Although ipilimumab prolonged survival of many patients, it wasn't as successful at a traditional measure of effectiveness: eliminating tumors. Just 3 of the 540 patients who took ipilimumab in the main trial saw their tumors disappear.
"In the long run, we've got to make that better," said Patrick Hwu, chairman of the melanoma medical oncology department at M.D. Anderson Cancer Center. Dr. Hwu expects further progress by combining ipilimumab with other agents under development, and by developing tests to determine which patients would benefit from immunotherapy.
The effort to develop immunotherapies for cancer has been marked by fits and starts. Eventually researchers discovered that the body has a fail-safe mechanism that puts the brakes on the immune cells in order to avoid nasty side effects should the cells unnecessarily kick into overdrive.
It took the past two decades for researchers to identify the braking mechanism, a molecule called CTLA-4, and develop a compound that gets the immune system to lift its foot off this brake enough to sufficiently attack melanoma, said James Allison, chairman of Memorial Sloan-Kettering Cancer Center's immunology program, whose research on the CTLA-4 molecule's role paved the way for ipilimumab's development.
"We are now really beginning to realize the benefit of immunotherapy," said Jedd Wolchok, director of immunotherapy clinical trials at Memorial Sloan-Kettering, who was one of the ipilimumab lead investigators.
The last drug approved for metastatic melanoma was Interleukin-2 in 1998, now sold by Prometheus Laboratories Inc. That therapy activated the immune system without lifting the brakes. Ipilimumab is the first immunotherapy that does so to gain approval.
Ipilimumab's approval should help Bristol-Myers offset the loss of patent protection next year for blockbuster bloodthinner Plavix, which had $6.7 billion in sales in 2010, about a third of the company's overall revenue. By most estimates, sales of ipilimumab are expected to exceed $1 billion.
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