CHICAGO – Executives from Bristol-Myers Squibb and Roche Holding AG huddled around a desk at New York's Memorial Sloan-Kettering Cancer Center about six weeks ago to iron out details of a novel clinical trial.
The two global drug companies were contemplating a rare collaboration of their experimental treatments for advanced melanoma, hoping to turn what is often a death sentence into a disease that a patient could live with in relative comfort over years.
"They were not talking about competing or how to place one drug above the other but how to use them together," said Dr. Jedd Wolchok of Sloan-Kettering. Wolchok, who has worked on clinical trials for both drugs, hosted the meeting, which culminated in an agreement last week.
"This trial has a very significant meaning, not just because it brings together the two most exciting drugs in melanoma in a very long time, but because the trial was planned by two big pharma companies before either drug was approved," Wolchok said in a telephone interview.
The trial will see if Bristol's recently approved Yervoy, or ipilimumab, and Roche's experimental drug vemurafenib are safe and effective when used together. That would allow them to be prescribed as a drug cocktail, as is standard for treating AIDS, for example.
Vemurafenib is designed for tumors that have a mutation in a gene known as BRAF that allows melanoma cells to grow. About half of all melanomas have the genetic aberration. It has been shown to work quickly and dramatically, cutting the risk of dying within six months by 63 percent compared with chemotherapy, though the effect is often short-lived.
Yervoy works by spurring the immune system to fight off the cancer. While it only benefits about 10 percent of patients who take it, those who do respond often get benefit that can last for many years.
In separate trials released on Sunday at the American Society of Clinical Oncology meeting in Chicago, both drugs showed they could extend lives of patients with advanced melanoma, the most deadly form of skin cancer.
"My question is, if patients had their disease slowed down at the get-go by a drug like vemurafenib and we could the get disease to quiet down, would that allow more patients to benefit from a drug like ipilimumab?" Wolchok said.
TIME FOR A COCKTAIL
Researchers and patient advocates say getting rival companies to test combinations of their most promising drugs is the next important step in finding a cure for melanoma, which globally afflicts nearly 160,000 new people each year.
Advanced melanoma can quickly spread from the skin to internal organs, such as the brain. Once melanoma spreads, the average survival is typically six to nine months.
"What melanoma has been for so long is a big game of Whack- A-Mole," Tim Turnham, executive director of the Melanoma Research Foundation, said in a telephone interview. "You try something and it might work for a time, or it might not."
Turnham said the time has come to look for a cocktail.
"This is what made AIDS a chronic disease. This is what turned the corner with TB," Turnham said. "Everybody knows combination treatments are the answer."
Drug companies have balked at combining two experimental drugs before each one is approved, fearing it would make it more difficult to prove to regulators the safety of each drug individually.
But in December, the U.S. Food and Drug Administration issued a document to help guide companies considering testing experimental drugs in combination in the hope of getting new, more effective treatments approved sooner.
"Really, all the things we concerned ourselves with in the past—challenges of regulatory review, differences between companies—that has all been set aside in an era when we have drugs that are effective for previously a uniformly lethal problem, which is metastatic melanoma," Wolchok said.
Dr. Renzo Canetta, vice president of global development/ oncology at Bristol-Myers, which is sponsoring the combination study, said the regulatory hurdle notion is often an excuse.
"There is no current regulation that prevents anyone from doing that," Canetta said in an interview at the ASCO meeting. "It's not easy, but it is an issue of motivation."
Bristol-Myers has done several combination studies, including an early study of its targeted drug Erbitux in combination with Roche's Avastin in colon cancer.
Roche is particularly adept at overcoming competitive barriers when a rival's drug appears to be the best fit. The company last month struck a deal with Merck & Co to co-promote their hepatitis C medicines.
EARLY PROMISE
A GlaxoSmithKline study presented on Saturday showed the potential power of a melanoma drug cocktail.
The early-stage trial involved patients with a specific genetic mutation who were treated with drugs designed to block MEK (GSK212) and BRAF (GSK436), two components of the same pathway used by the cancer to drive tumor growth.
Of the 16 patients evaluated so far, 13 percent had tumor shrinkage and three had stable disease, for an overall response rate of 81 percent.
In five patients, the tumors were completely gone.
And the combination appeared to cut some of the toxic side effects—skin rashes and a mild form of skin cancer—seen when the drugs are used on their own.
Canetta said the promise of a more effective treatment must be tested in the context of a clinical trial, especially because both the Bristol and Roche drugs cause side effects.
"We need really to study how the two drugs interact, whether there is overlapping toxicity," Canetta said.
In fact, Canetta is urging doctors not to combine the drugs in patients on their own once Roche's vemurafenib becomes publicly available, which is expected by year-end.
"The law in this country allows physicians to prescribe whatever they want. We are warning them be careful because there is not enough experience with the two drugs," he said.
Turnham said another study combining an approved drug and an experimental treatment will also soon be announced. He said recent successes in melanoma research are worth celebrating but that they were incremental advances at best.
"We're not anywhere close to where we need to be in handling this cancer. The only way we are going to get close is doing it a different way," he said.
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