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Bristol-Myers Skin Cancer Drug Prolongs Survival

The Bristol drug uses a patient's own immune system to fight skin cancer, boosts survival by 3.5 months.

Follow all the action from the American Society of Clinical Oncology (ASCO) annual meeting in real time at Adam Feuerstein's ASCO live blog.



) --A drug from

Bristol-Myers Squibb

(BMY) - Get Bristol-Myers Squibb Company Report

that harnesses the immune system to fight cancer reduced helped patients with advanced melanoma live, on average, 3.6 months longer and reduced their risk of death by as much as 34%, according to results from a phase III study released Saturday at the

American Society of Clinical Oncology

(ASCO) annual meeting.

Bristol is clearly excited about its melanoma drug, known as ipilimumab, announcing last March that the results from this 676-patient, phase III study were positive and that the company planned to apply for approval later this year.

Bristol kept details of the study under wraps, however, making today's announcement at the ASCO meeting a highly anticipated event for both melanoma researchers and Wall Street investors.

"Over the last 30 years, randomized clinical trials have repeatedly failed to demonstrate an improvement in overall survival in patients with advanced melanoma. It's an extremely difficult disease to treat," said lead researcher Dr. Steven O'Day of the University of Southern California Keck School of Medicine. 'These results are an exciting advance, both for patients with advanced melanoma and for the field of cancer immunology."

Ipilimumab is a monoclonal antibody that works by sparking a patient's own immune system to target and kill cancer cells. So-called immunotherapy drugs have been tested against numerous cancers for years with little success -- and that includes previous studies of Ipilimumab. The cancer immunotherapy field found its first winner with



prostate cancer vaccine Provenge, which was approved in late April. Now, Bristol-Myers may be following in Dendreon's footsteps with Ipilimumab.

Improving survival is the gold standard for any cancer study, but the ipilimumab study lacked a comparison to a placebo or true control, which makes the results harder to interpret.

Patients with previously treated melanoma were divided into three groups. One group received a peptide vaccine known as gp100; a second group of patients received ipilimumab plus a placebo; while a third group received ipilimumab plus the gp100 vaccine.

The gp100 vaccine was also designed to stimulate the immune system against cancer but previous studies showed it to be ineffective, which is why it was used as comparator in the study.

After treatment, patients given with the gp100 vaccine alone reported a median overall survival of 6.4 months. Patients treated in both ipilimumab arms lived an average of 10 months. The 3.6-month survival benefit in favor of ipilimumab over the gp100 vaccine alone was statistically significant.

Expressed differently, the "hazard ratio" for the two ipilimumab arms were 0.64 and 0.68, which means the risk of death was reduced by 34% and 32% in patients treated with either ipilimumab alone or ipilimumab plus the gp100 vaccine, respectively.

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The similar survival result for the ipilimumab alone and ipilimumab-vaccine treatments is the best outcome for Bristol because it suggests that the vaccine is essentially a placebo and has no added benefit for patients. Reinforcing that belief, researcher presenting the ipilimumab data Saturday at an ASCO press conference said the 6.4-month median overall survival observed in patients treated with the gp100 vaccine alone was similar to survival results seen with placebos in past melanoma studies.

The 10-month survival time for ipilimumab-treated patients, however, is also similar to survival times reported for other drug combinations used in past melanoma studies. For example, a phase III study of

Onyx Pharmaceuticals'


Nexavar plus chemotherapy disappointed in 2008 by failing to demonstrate a survival benefit over chemotherapy alone. Yet treatment in both arms of the study yielded a median overall survival of 10.5 months -- more than what ipilumumab was able to produce in this phase III study.

"Anything less than 11 months on median survival should raise questions," said Leerink Swann analyst Seamus Fernandez in a recent investor note, referring to the ipilimumab survival results.

"Because the

ipilimumab study lacks a true control, we believe ipilimumab must exceed historical controls in second-line metastatic melanoma to satisfy investors and regulators," Fernandez added. He has a market perform rating on Bristol, which closed Friday at $TK.

Another curiosity of the Bristol study is the average time after which tumors start to grow again -- progression-free survival -- was the same regardless if patients were treated with ipilimumab (2.9 months), ipilimumab plus the gp100 vaccine (2.8 months) or the gp100 vaccine alone (2.8 months.)

One possible explanation is that immunotherapies like ipilimumab don't work immediately because it takes some time for a patient's immune system to activate against tumors. A similar effect is believed to be at work with Dendreon's Provenge.

In fact, when researchers in the Bristol phase III study checked patients for tumor growth after six months, they found 30% of ipilimumab patients with no disease progression compared 11% of patients treated with the vaccine alone.

In past studies of ipilimumab, patients saw their tumors grow at first, which made doctors think the drug wasn't working. It wasn't until these patients were followed for longer that their tumors started to shrink and doctors noticed that they were living longer.

On the safety side, ipilimumab was generally well tolerated with between 10-14% of patients experiencing severe side effects like rash and inflammation of the colon compared to 3% of vaccine-treated patients.

A full presentation of the ipilimumab data in melanoma will be made Sunday during ASCO's plenary session.

-- Reported by Adam Feuerstein in Boston.

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Follow all the action from the American Society of Clinical Oncology (ASCO) annual meeting in real time at Adam Feuerstein's ASCO live blog.

Adam Feuerstein writes regularly for In keeping with TSC's editorial policy, he doesn't own or short individual stocks, although he owns stock in He also doesn't invest in hedge funds or other private investment partnerships. Feuerstein appreciates your feedback;

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