Merck & Co. (MRK), Bristol-Myers Squibb Co. (BMY) and Roche Holding AG (ROG) have opened a new front against cancer with the next generation of experimental drugs that use the human immune system to seek and destroy tumor cells.
The new therapies have the potential to reap billions of dollars in sales while lengthening patient remissions, said doctors and analysts awaiting study results to be released this week as part of the American Society of Clinical Oncology meeting that starts May 31.
Building on the success of Bristol-Myers’ Yervoy drug for melanoma that reached the market in 2011, drugmakers are devising more potent immune therapies or combining treatments for maximum effectiveness. They are also testing the new medicines in more types of cancers, including lung and breast.
If the new generation of immune therapies lives up to its promise, “this is going to be a paradigm shift for treating cancer,” said Merck senior vice president Gary Gilliland in an interview. “We are pretty good at shrinking tumors, but not good at getting rid of them. Immune therapy is a way to begin to approach that.”
It will take at least a year before scientists will be able to determine whether the new drugs can extend lives. Still, the strategy offers scientists the first major new avenue for attacking cancer in a decade. In recent years, researchers have focused on treatments that targeted specific genetic processes that create uncontrolled cell growth. While this approach produced some successes, advanced tumors are often able to evade attack within a few months by producing mutations.
Now many believe that by strengthening the immune system’s ability to identify and kill cancer cells, they can broaden the attack so it will fight any dangerous malignancy.
“You’re setting up a fair fight” with the disease, said Nils Lonberg, a senior vice president at Bristol-Myers, in a telephone interview. “The immune system is just as adaptable as the cancer.”
The financial stakes are high. The targeted drug Avastin, for instance, made by Roche, had $5.8 billion in sales last year for use against colon and other tumors. Nivolumab, a new immune-boosting cancer drug candidate that Bristol-Myers is developing could generate an “Avastin-like sales number, maybe even better,” if it’s found to work in lung cancer, said Tony Butler, a New York-based analyst at Barclays Plc (BARC), by phone.
The new drugs are designed to prevent flicking what is essentially an off switch, called PD-1, for immune system T-cells, the body’s key defenders against attacks from dangerous germs, infections or other biological bad guys.
“Tumors have this Harry Potter cloak of invisibility,” Merck’s Gilliland said. The new class of drugs “lifts the cloaking device and allows the immune system to attack.”
Yervoy from Bristol-Myers was the first drug proven to extend survival in advanced melanoma, the most deadly form of skin cancer.
Data presented in September on the medicine showed it doubled the number of patients that survived four years to 19 percent. Now, the New York-based drugmaker is seeing positive early results from nivolumab, a new experimental immune therapy for skin, lung and kidney tumors.
In June of last year, Bristol-Myers reported that nivolumab shrank tumors in people with advanced lung, kidney and skin cancer in 18 percent to 28 percent of patients who had failed on other treatments.
So far, nivolumab is leading the next wave of immune-boosting cancer medicines with six final-stage trials in 3,300 patients with lung cancer, kidney tumors and melanoma.
At least six other companies are testing immune therapy drugs in patients with advanced cancer, said Jedd Wolchok director of immunotherapy at the Ludwig Center at Memorial Sloan-Kettering Cancer Center in New York. Wolchok’s team is testing seven treatments from six companies in 10 trials, up from just two drugs five years ago, he said in an interview.
“A couple of years ago the big story was that immunotherapy can work,” he said, referring to Yervoy’s initial success. ‘Now immunotherapy has entered the mainstream.”
Merck, of Whitehouse Station, New Jersey, is in second-stage testing on its immune therapy, lambrolizumab, in melanoma. If successful, the 500-patient trial may be large enough to gain approval from U.S. regulators without completing the usual required third-stage of testing, putting it in a virtual dead heat with Bristol’s nivolumab in melanoma.
In November, doctors at a melanoma research conference presented early data showing lambrolizumab shrank tumors in 51 percent of patients with advanced skin tumors. Merck has also begun studies of its drug in cancers of the lung, head and neck, and breast.
The best way to keep the PD-1 system from turning off immune cells is not yet clear, which is why the upcoming trial results are so important. In addition, both Bristol-Myers and Merck compounds have shown side effects including the potential for lung inflammation in some cases.
Meanwhile, a medicine under development at the Basel, Switzerland drugmaker Roche targets a related protein on tumor cells called PD-L1, which the company believes may be a safer approach. Results from an initial trial of the drug in patients with various types of advanced cancer will be presented at the meeting. Based on the results to date, Roche plans to begin a final-stage study of its drug in lung cancer.
Merck’s Gilliland said patient demand for the PD-1 drugs is so intense that the company had to step up the pace of opening trial sites. Some patients with advanced melanoma have skipped over approved treatments to jump right to Merck’s experimental drug, he said.
The enthusiasm is understandable because immune drugs hold the promise of producing long-lasting remissions, said Michael Gordon, director of research at Pinnacle Oncology Hematology, in Scottsdale, Arizona, who has been involved in testing the Roche drug.
Cancer doctors “are accustomed to moving from one therapy to another” as tumors rapidly develop resistance,” he said in a telephone interview. “It is generating tremendous excitement to have a drug class that might well be able to provide long term control of metastatic cancer.”
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