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Melanoma/ZGEN -

given the # of failed candidates in this indication it's not a shocker that no one has ponied up the kind of money ZGEN wants to license the candidate

According to this forbes article Melanoma is now "the hot area" for development. ZGEN has dropped pretty dramatically since the "flash crash". Is the prospect of positive "ipi" results adversely affecting ZGEN or is there some other reason for this sharp drop in share price?

Bristol's Mysterious Melanoma Medicine
June 2, 2010 - 1:10 pm
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Robert LangrethBio | Email
Robert Langreth is a senior editor at Forbes, in charge of health care coverage
Bristol-Myers Squibb could be the star of the show at this weekend's confab of cancer doctors at the American Society of Clinical Oncology in Chicago.

The company is scheduled to present new data on its leukemia drug Sprycel seeking to show that it is better than Novartis's blockbuster Gleevec. By far its most important result will be the first survival data for its mysterious melanoma drug ipilimumab. The drug has been in testing for years. Earlier this year, the company said it plans to apply for approval based on the results of a giant 700 patient trial, making Wall Street eager to see the results.

If it works, it could help open a new front on the war on cancer: drugs that spur the immune system to attack the disease. The results are widely assumed to be positive, but will they be positive enough for regulators? The unusual design of the Bristol study means that it could yield all sorts of murky, hard-to-interpret results. It could get complicated. A similar drug from Pfizer called tremelimumab failed to improve survival in a large trial of melanoma patients.

"The data is probably going to be good," predicts Memorial Sloan-Ketttering Cancer Center melanoma expert Jedd Wolchok. "If that is the case, this would be the first drug to show a survival advantage in a randomized trial in metastatic melanoma." He says the drug could be used on about 7000 to 8000 patients with advanced melanoma every year.

But the potential for the drug goes well beyond melanoma. Its mechanism isn't specific to melanoma and could applied broadly to numerous other types of cancers, including lung and prostate cancer. If it is approved in melanoma, "we will see a flurry of trials" of ipilimumab in other tumors, says UCLA's Antoni Ribas.

Ipilimumab is being watched closely because it works by a totally new mechanism to spur the body's immune system against the disease. Instead of attacking tumor cells directly, it aims to turn off the brakes on the immune system so that immune celks will attack and kill cancer. In early trials, ipilimumab produced spectacular responses in close to 10% of patients. Some of them are alive and well today.

But didn't help many others, and it works in mysterious ways. Sometimes the drug does nothing at first and tumors continue to grow. Then, months later, all of a sudden the immune system kicks in and the tumors start shrinking. Researchers don't understand why.

The new result could be murky. The new trial will avoid complicated issues of tumor shrinkage by comparing overall survival of patients who got ipilimumab to those who didn't, but there is no comparison to a placebo or other well-understood treatment. This will make analysis of the result trickier.

Patients were divided into three groups: one got a vaccine called gp100, another got only ipilimumab, and a third got both vaccine and ipilimumab. In analyzing the trial, researchers will look to see whether patients who recieved ipilimumab lived longer than those who got the vaccine alone.

"Nobody expected the vaccine alone to have much of an effect, you could consider that a placebo of sorts," says Memorial Sloan-Kettering's Wolchok, who was involved in tests of the drug. "All they are looking for is whether the ipilimumab alone arm is better than the vaccine alone arm." It would also be good if the vaccine plus ipilimumab arm showed similar survival time to ipilimumab alone; this would indicate that the vaccine had little effect. On the other hand, any hint that the vaccine has detrimental effects on survival could muddy the water and confuse the results of the trial.

Given the lack of a normal control group, regulators will want to see that patients who got ipilimumab in the trial lived longer than similar melanoma patients in previous chemotherapy trials, according to a note from Seamus Fernandez of Leerink Swann. Past trials of drugs in similar patients have shown survival times of up to 10.5 months, and regulators will want to make sure that ipilimumab produces survival times that exceed these. "Anything less than 11 months on median survival should raise questions," Fernandez predicts.

Bristol will have to work fast to get ipilimumab approved, because melanoma has suddenly become a hot area for drug devlepment. Another type of melanoma drug from Roche showed promising results last year and is moving into final stage trials. "Melanoma is becoming the poster child of cancer drug development, when it used to be the graveyard," says ULCA's Ribas.

http://blogs.forbes.com/sciencebiz/2010/06/bristols-mysterious-melanoma-medicine/?partner=yahootix