Roche Leads Deadly Skin Cancer Turnaround to ‘Golden Age’ of Drug Research
By Robert Langreth and Michelle Fay Cortez

Cheryl Stratos says she was given only six to eight months to live by her doctors after melanoma, the deadliest of skin cancers, spread in her body.

Stratos, a 46-year-old from McLean, Virginia, who owns an advertising sales company, began using the drug vemurafenib in an experimental trial in February 2010. Last month, the tumors in her liver and lungs had become barely detectable, “giving me my life back,” Stratos said.

The treatment, from Swiss drugmaker Roche Holding AG (ROG) and Daiichi Sankyo Co. of Tokyo, is part of a revolution in cancer biology. Metastatic melanoma has long been a death sentence, killing 8,700 Americans a year. Now medicines from Roche, Daiichi, Bristol-Myers Squibb Co. (BMY) and GlaxoSmithkline Plc (GSK) are among a dozen in advanced testing that are starting to rewrite the prognosis for patients like Stratos.

“The science has exploded,” Stephen Hodi, director of the melanoma center at Dana-Farber Cancer Institute in Boston, said in a telephone interview. “We are entering a golden age of melanoma therapies.”

New drugs are giving researchers an unprecedented ability to combine treatments and prolong survival, Hodi said. While the therapies don’t provide a cure, they show how progress can be made by aiming at the genetics of tumors or harnessing the body’s defenses to fight off invading cancer cells.

Data on the newest melanoma drugs are among the more than 2,500 studies on cancer treatments that will be presented at the meeting of the American Society of Clinical Oncology that starts June 3 in Chicago.

$1.5 Billion in Sales

For pharmaceutical companies, success in melanoma also may lead to billions in sales. New York-based Bristol-Myers’s Yervoy, the first to extend advanced melanoma survival when it was approved March 25, costs $120,000 for a standard course of four doses and may reach $1.5 billion in sales by 2015, according to Bloomberg survey of four analysts.

Vemurafenib, the drug from Stratos’s trial, may generate 700 million Swiss francs ($796 million) in revenue by 2015, according to Jack Scannell, an analyst with Sanford C. Bernstein & Co. in London.

Roche, based in Basel, Switzerland, has submitted the therapy for regulatory approval in the U.S. and Europe. Doctors are set to report at the cancer meeting that vemurafenib helps patients with advanced melanoma live longer.

Glaxo, with three drugs in the final stage of development for melanoma, will present at the meeting one of the first studies combining two experimental medicines attacking different molecules that encourage cancer growth.

Combination Therapy

The study combines Glaxo’s GSK2118436 drug, which blocks one mutated protein that spurs melanoma’s spread, with a treatment that thwarts a related growth-promoting molecule to keep cancer from evading treatment, said Perry Nisen, a senior vice president at the London-based drugmaker.

The study may provide a clue to whether the approach to control resistance is viable, said Ramya Kollipara, an analyst at Decision Resources in Burlington, Massachusetts.

Survival from advanced melanoma may double over the next five years to ten years as new treatments come online, from 10 months to 20 months, said Antoni Ribas, an oncologist at the University of California, Los Angeles, who treats Stratos.

“There is no doubt that melanoma is the hottest cancer in oncology,” he said in an e-mail. “It is a triumph of science translated to patients with unprecedented benefits.”

The excitement is tempered by decades of failure. Until this year, there were only two approved drugs for treating advanced melanoma, and neither had been proven to prolong life. Melanoma drugs from companies including New York-based Pfizer Inc. (PFE), the world’s largest drugmaker, Bayer AG (BAYN) and Glaxo have stumbled in final development stages.

Chicago Cubs Fan

“Being a melanoma doctor is not unlike being a Chicago Cubs fan,” said George Sledge Jr., president of the American Society of Clinical Oncology and an oncology professor at Indiana University’s Cancer Center, referring to the U.S. baseball team’s 103 years without winning a World Series.

“For the first time, though, we have not one but two drugs that are moving the needle for melanoma,” he said of Yervoy and vemurafenib, the most-advanced treatments for skin cancer. “This is a sea change for the melanoma guys.”

The disease strikes 68,000 Americans each year, according to the American Cancer Society. While patients with early stage disease respond well to treatment, the five-year survival rate for those with cancer that has spread is 15 percent.

The new medicines have limitations. Yervoy has led to long- lasting remissions in a small minority of patients, and yet most patients don’t get dramatic benefits. It extended life by a median of four months in the trial that led to its approval, and can cause fatal inflammation of the intestine and other organs.

Beyond Expectations

Vemurafenib and Glaxo’s similar GSK2118436 have shrunk tumors at a rate “beyond our most optimistic expectations,” Ribas said in an interview. Yet patients on vemurafenib have often stopped responding after six or seven months, he said. The drugs are linked to an increased risk of other, less serious skin cancers.

Still, advances in melanoma show how researchers can make progress against even the toughest cancers by attacking tumors on multiple fronts, Hodi said.

Drugs like vemurafenib aim to slow cancer by hitting a mutation in a protein called BRAF that drives growth in half of all melanomas, including Stratos’s tumors. Yervoy and similar medicines in trials work indirectly by unleashing the body’s immune system to attack and kill cancer cells.

A crucial clue leading to vemurafenib and GSK2118436 came in 2002 when British gene researchers found that some patients had a mutation in the growth-promoting gene BRAF.

First Gene Aberration

“That was the first frequent genetic aberration in melanoma” that could easily be targeted with drugs, said Jedd Wolchok, a melanoma expert at Memorial Sloan-Kettering Cancer Center in New York, in a telephone interview. “The pharma companies really went after that.”

One company that jumped on the lead was closely held Plexxikon Inc. of Berkeley, California. The company was purchased Feb. 28 by Daiichi for up to $935 million.

Company scientists made a crystal structure of the mutant protein that enabled them to test it against potential compounds, and by 2005 had devised the drug vemurafenib that blocked it. Human trials with partner Roche began in 2006.

Three years later, an Internet search for a clinical trial brought vemurafenib to Stratos. After Stratos failed to qualify for trials of vemurafenib at Sloan-Kettering because she had not tried chemotherapy, her husband, Michael Stratos, called “every hospital” until he tracked down Ribas who was performing the trial at UCLA.

Stratos started on the medicine on Feb. 28, 2010, and has had side effects including a “horrible burning flaming rash all over” and flu-like symptoms, she said.

Two months later, the tumors had shrunk 30 percent on a computed tomography scan. They continued to gradually shrink and a PET scan last month showed virtually no activity in her remaining small tumors, Stratos said.

“It is amazing,” she said. “I am one of the lucky ones, one of the outliers it is working for long term.”

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