Cancer researchers are growing increasingly enthusiastic about harnessing the body’s own immune system to fight tumors

May 15, 2013

Melanoma Treatment Harnesses Immune System to Combat Cancer Cells


Cancer researchers are growing increasingly enthusiastic about harnessing the body’s own immune system to fight tumors. And new research shows that two drugs that use this approach may be even better than one. Researchers reported on Wednesday that a combination of two drugs from Bristol-Myers Squibb shrank tumors significantly in about 41 percent of patients with advanced melanoma in a small study. In few of the 52 patients in the study, tumors disappeared completely, at least as could be determined by imaging.

“I think it was really the rapidity and the magnitude of the responses that was impressive to us,” Dr. Jedd D. Wolchok of the Memorial Sloan-Kettering Cancer Center, said in a telephone news conference organized by the American Society of Clinical Oncology.Dr. Wolchok’s study, and others on the immune system drugs, will be perhaps the most closely watched items at the society’s annual meeting, which begins on May 31 in Chicago.

The drugs are also generating huge interest on Wall Street, which projects billions of dollars in annual sales. While Bristol is generally considered to have a lead, Merck and Roche are not far behind with similar drugs.

Data released Wednesday from an early-stage study of Roche’s drug, which is known as MPDL3280A, showed significant tumor shrinkage in 21 percent of 140 patients who had a variety of cancers including lung, melanoma and kidney cancer.

The studies are small and they did not compare the drugs with a placebo or with another treatment, and it is unclear if they will lengthen lives. Moreover, it is unclear how long the effects will last, though there are signs that for many patients, it could be a year or more.

Cancer cells often successfully hide from the body’s immune system by preventing T-cells from attacking them. The new drugs basically work by disabling brakes on the immune system, allowing the T-cells to attack the tumors.

One of the drugs in Bristol-Myers’ combination is Yervoy, which was approved as a treatment for melanoma in 2011. Yervoy disables an immune system brake called CTLA-4. It shrinks tumors in only about 10 percent of patients, but the effects can last for a long time.

The other drug in its combination is nivolumab, which is not yet on the market. It disables a brake known as PD-1, which sits on the surface of T-cells. Tumors can produce a protein called PD-L1, which binds to PD-1 and makes the T-cells inactive.

Nivolumab, and the drug being developed by Merck, called MK-3475, are antibodies that bind to PD-1, while Roche’s drug binds to PD-L1. It is not clear yet which approach is better.

It may be possible to test tumors for the presence of PD-L1, and use the drugs mainly for those patients, where it is expected to work more effectively.

It is also not clear yet how many types of tumors the drugs will work for. All the companies are targeting melanoma, a deadly skin cancer, because there is evidence that it is sometimes controlled spontaneously by the immune system. The companies also have data for lung and kidney cancer. Roche’s study showed some effect in colorectal and head and neck cancer as well.

Bristol-Myers’s stock rose 5 percent on Wednesday, even though the results of the study were not released until 6 p.m., after the close of regular trading.

Mark Schoenebaum, the pharmaceutical analyst at ISI Group, said investors were hoping the combination of the two Bristol drugs would significantly shrink tumors in at least 50 percent of patients.

He said in a note on Wednesday that the overall shrinkage rate was perhaps a bit below expectations but added that for many patients, the shrinkage was more than 80 percent.

“The point is that the depth of those responses is pretty incredible,” he wrote.

Some experts say that tumor shrinkage, a measure that evaluates conventional chemotherapy drugs that poison cancer cells, may understate the effect of these new drugs.

“Sometimes it takes awhile for the immune system to be revved up,” said Dr. Gary Gilliland, who leads cancer drug development at Merck.

May 15, 2013

New Cancer Drugs Harness Power of Immune System


Two early-stage drug studies from Bristol-Myers Squibb Co. BMY -3.52% and Roche Holding AG ROG.VX -0.81% provided fresh evidence that harnessing the power of the immune system is emerging as a promising weapon against cancer.

In the Bristol-Myers study, using a two-drug combination that targets the immune system resulted in “rapid and deep tumor regressions” in nearly one-third of 52 skin cancer patients treated with the combination, researchers said. The drugs were melanoma treatment Yervoy, already on the market, and the company’s experimental drug nivolumab.

The combination was more effective than each drug given alone, said Jedd Wolchok, an oncologist at Memorial Sloan-Kettering Cancer Center in New York, who led that study.

The Roche trial tested a single agent currently known as MPDL3280A. Overall, tumors in 29, or 21%, of patients evaluated responded to the drug; tumors hadn’t progressed in 26 of the patients, including some who had been on the treatment for more than 15 months.

Patients with advanced lung, kidney and skin cancer were among those who responded favorably, said Roy Herbst, an oncologist at Yale University, who headed the Roche study. That suggests immunotherapy, as the strategy is called, may have broad application across many types of tumors.

The three drugs in the studies essentially work by releasing the brakes on the immune system to allow it to recognize and go after tumor cells.

Scientists have been trying for decades to understand why the body’s immune system didn’t see cancer cells as the enemy and attack them. Recent discoveries revealed that tumors are adept at cloaking themselves by hijacking the body’s own mechanism for preventing the system’s T-cells, the infection- and disease-fighting cells of the immune system, from running amok against healthy tissue.

The drug findings were unveiled on Wednesday in a news conference ahead of the annual meeting of the American Society of Clinical Oncology, which begins May 31 in Chicago.

Though the studies are small, the results reflect rapidly growing conviction that immunotherapy is the next big front in the war on cancer. Merck & Co., for instance, is also moving quickly with a candidate that targets the immune system.

In advance of the findings released on Wednesday, Leerink Swann issued a note to investors predicting that the three companies’ drugs combined could collectively generate $10 billion in peak annual sales. More broadly, Leerink believes the “immuno-oncology” drug market could amount to a $20 billion category annually, putting it on a par with the cholesterol-lowering statin market at its height.

Bristol’s drug Yervoy inhibits the function of a molecule called CTLA-4. The experimental agent called nivolumab and Merck’s drug, known as MK-3475, each work against a different mechanism called PD-1. The new Roche drug, being developed by its Genentech unit, inhibits a molecule called PD-L1.

Side effects of the drugs include inflammation associated with the immune system’s activation against tumors, but researchers said they were either resolved or were treated without serious consequence.

So far, only a fraction of patients have responded to the treatments, but the benefits have occasionally been dramatic, with some melanoma patients on Yervoy, for instance, surviving several years after one course of treatment.

“It’s a minority of patients, but the responses are durable once you’ve got them,” said James Allison, a researcher at MD Anderson Cancer Center whose work was instrumental in discovering the immune-system brakes and in the development of Yervoy. He is scientific co-founder of a company called Jounce Therapeutics Inc., which is focused on developing immunotherapy drugs.

Based on the new resultsRoche is planning to launch a late-stage trial of its PD-L1 inhibitor in lung-cancer patients, while Bristol-Myers is moving its combination regimen into late-phase studies as well.

Merck’s PD-1 blocker, being tested in melanoma patients, was recently given “breakthrough” designation by the Food and Drug Administration, which could speed its path through the regulatory process.

Some experts believe the immunotherapy agents hold particular promise in being paired with drugs that specifically target genetic mutations driving the tumors.

“Since you’re treating the immune system, and not the cancer, this sort of approach should work against all kinds of cancer,” Dr. Allison said.

Pfizer Inc., PFE -0.62% for instance, doesn’t have any PD-1 or PD-L1 drugs in its pipeline, but Garry Nicholson, president of its oncology unit, said the company is interested in studying them in combination with its own targeted cancer drugs. “There are multiple ways of working out these combinations,” he said.

About bambooinnovator
Kee Koon Boon (“KB”) is the co-founder and director of HERO Investment Management which provides specialized fund management and investment advisory services to the ARCHEA Asia HERO Innovators Fund (, the only Asian SMID-cap tech-focused fund in the industry. KB is an internationally featured investor rooted in the principles of value investing for over a decade as a fund manager and analyst in the Asian capital markets who started his career at a boutique hedge fund in Singapore where he was with the firm since 2002 and was also part of the core investment committee in significantly outperforming the index in the 10-year-plus-old flagship Asian fund. He was also the portfolio manager for Asia-Pacific equities at Korea’s largest mutual fund company. Prior to setting up the H.E.R.O. Innovators Fund, KB was the Chief Investment Officer & CEO of a Singapore Registered Fund Management Company (RFMC) where he is responsible for listed Asian equity investments. KB had taught accounting at the Singapore Management University (SMU) as a faculty member and also pioneered the 15-week course on Accounting Fraud in Asia as an official module at SMU. KB remains grateful and honored to be invited by Singapore’s financial regulator Monetary Authority of Singapore (MAS) to present to their top management team about implementing a world’s first fact-based forward-looking fraud detection framework to bring about benefits for the capital markets in Singapore and for the public and investment community. KB also served the community in sharing his insights in writing articles about value investing and corporate governance in the media that include Business Times, Straits Times, Jakarta Post, Manual of Ideas, Investopedia, TedXWallStreet. He had also presented in top investment, banking and finance conferences in America, Italy, Sydney, Cape Town, HK, China. He has trained CEOs, entrepreneurs, CFOs, management executives in business strategy & business model innovation in Singapore, HK and China.

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