May 19, 2024

Approval for Drug That Treats Melanoma

The drug, Yervoy, was developed by Bristol-Myers Squibb and is a novel type of cancer drug that works by unleashing the body’s own immune system to fight tumors.

“This is really the first time in the melanoma field that there is a drug that extended survival in a meaningful way,” said Dr. Gerald P. Linette, an assistant professor of medicine at Washington University in St. Louis, who participated in a clinical trial of the drug.

In that randomized clinical trial, patients with metastatic melanoma treated with Yervoy lived a median of about 10 months, compared with 6.4 months for patients in a control group, who received a treatment believed to have had little effect.

Bristol-Myers said it would charge $120,000 for a complete course of treatment, which consists of four infusions given over a three-month period.

That price could spur continued debate about the cost of cancer drugs that prolong survival by only a few months on average.

More than 20 percent of the people who received Yervoy in the trial lived at least two years, and some of them much longer. But there is no way at present to predict which patients will benefit from the drug.

A spokesman for Bristol-Myers said some other drugs for melanoma cost nearly as much as Yervoy, without having demonstrated prolonged survival. He also said the company would offer financial support to certain patients.

There were about 68,000 new cases of melanoma in the United States last year and 8,700 deaths, according to the American Cancer Society. The number of cases has been rising, probably because of sun exposure without proper protection.

Melanoma detected early as a mole on the skin can be surgically removed. But once it has metastasized, or spread, it is very difficult to treat, and various drugs have failed in clinical trials.

The last drug approved was interleukin-2 in 1998, but it is so toxic it is rarely used. Neither it nor the other approved drug, dacarbazine, has clearly demonstrated improved survival.

But another drug, being developed by Roche and Plexxikon, has also recently been found to prolong lives of patients with metastatic melanoma in a large clinical trial, according to those companies. They have not provided details of the results but said they hoped to apply later this year for its approval.

Shares of Bristol-Myers rose 86 cents to $27.29, in part because the price of the drug is higher than many analysts had expected and also because the approval allows for wider use of the drug than was predicted.

The company’s trial tested the drug in patients who had already failed to benefit from treatment with another drug. But the F.D.A.’s approval also allows Yervoy to be used for previously untreated patients with metastatic melanoma. Bristol had announced on Monday that a new study showed Yervoy also improved survival when used for previously untreated patients.

Robert Hazlett, an analyst at BMO Capital Markets, said annual sales could eventually exceed $1 billion. Bristol needs sales from new products to help offset the loss of patent protection next year on Plavix, its huge-selling anticlotting drug.

Yervoy is an example of an emerging class of treatments known as immunotherapy that harness the body’s own immune system to fight tumors.

Last year, the F.D.A. approved what was considered the first of these treatments, the prostate cancer drug Provenge, developed by Dendreon. Provenge is sometimes called a vaccine because it trains a patient’s immune system to attack the cancer.

Yervoy, by contrast, works by essentially disabling a brake on the immune system.

Because it is not specific for any type of tumor, it might conceivably be effective for many types, though this is yet to be proved in clinical trials.

“The treatment is of the immune system, it’s not of the tumor,” said James P. Allison, head of the immunology program at the Memorial Sloan-Kettering Cancer Center in New York, whose work led to the development of the drug.

The drawback is that loosening the restraints on the immune system can lead to dangerous side effects, the most worrisome being colitis and diarrhea, but also hepatitis, endocrine dysfunction and skin problems. The F.D.A. said that 12.9 percent of patients treated with Yervoy suffered severe or fatal autoimmune reactions.

“It’s not your typical chemotherapy toxicity,” said Dr. Jeffrey A. Sosman, a professor at the Vanderbilt-Ingram Cancer Center in Nashville. He said oncologists would have to be trained to recognize the side effects and treat them quickly with corticosteroids.

The effect of Yervoy on cancer is also different from chemotherapy drugs, which can quickly kill some cancerous cells. With Yervoy, it can take weeks for the immune system to mount its attack.

“Many people with really aggressive melanoma don’t have that time,” Dr. Sosman said.

For most patients, tumors don’t shrink immediately and may even grow, making it hard to tell if the drug is working.

When Donna Laurin of Glover, Vt., began taking the drug, melanoma spots on her right leg began proliferating wildly, making her worry.

But after four doses, the spots began disappearing. “I have no sign of melanoma in my leg,” Ms. Laurin, 56, said. The effect so far has lasted seven weeks.

Yervoy works by blocking a protein on the surface of T cells, the soldiers of the immune system, called cytotoxic T-lymphocyte antigen 4, or CTLA-4. The protein inhibits the action of the T cells.

Bristol already sells a drug, Orencia, that essentially provides CTLA-4 to patients with rheumatoid arthritis in order to reduce their immune system’s attack on their joints. Yervoy works the opposite way, blocking CTLA-4 to unleash the immune system.

Dr. Allison and colleagues, working at the University of California, Berkeley, in the mid-1990s, discovered the role of CTLA-4 and found that blocking it helped mice fight tumors.

Drug companies were not that interested. “The idea was so new, it was hard to get somebody to take it,” Dr. Allison recalled in an interview this week.

The university finally signed a deal in 1998 with NeXstar Pharmaceuticals, which in turn sublicensed rights to Medarex, another biotechnology company.

Medarex developed a monoclonal antibody, a type of protein, to block CTLA-4 and began testing it in partnership with Bristol-Myers. Bristol-Myers then acquired Medarex for $2.4 billion in 2009.

NeXstar, meanwhile, was acquired in 1999 by Gilead Sciences, which gave up its rights to royalties on Yervoy for a payment of $8.5 million from Medarex.

The financially troubled Berkeley will receive royalties, however. The amount is being kept confidential.

“I feel great because it’s been a long haul,” said Dr. Allison, who plays blues harp in an amateur band he named the Checkpoints, after immune system checkpoints like CTLA-4.

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