Drugs Show Promise Slowing Advanced Melanoma

The drugs represent success in two new approaches to combating cancer: one by attacking a specific genetic mutation that accelerates tumor growth; the other by unleashing the body’s immune system to fight the disease

“This is an unprecedented time of celebration for our patients,” Dr. Lynn M. Schuchter, a melanoma specialist at the University of Pennsylvania, told reporters Sunday in Chicago at the annual meeting of the American Society of Clinical Oncology, where the results were presented.

The drugs do not cure melanoma, except perhaps in rare cases. But experts said they might add two to several months to the expected lifespans of people with advanced melanoma. Right now people with metastatic melanoma — meaning it has spread to distant organs — typically live 6 to 10 months.

In one trial, 84 percent of patients taking the experimental drug vemurafenib (pronounced vem-yoo-RAF-en-ib) were still alive after six months, compared with 64 percent of those getting an older chemotherapy drug, dacarbazine. Using another statistical measure, the risk of dying was reduced 63 percent.

The effect was so marked that the trial was stopped early for ethical reasons, so that patients in the control group could be offered the new drug. Because of that, researchers do not yet know the median survival.

“You don’t need to wait for 50 percent of 675 patients to die to conclude that one drug is much better than the other,” said Dr. Antoni Ribas of the University of California, Los Angeles, who was an investigator in the trial and has been a consultant to the developer of the drug.

The other new drug, ipilimumab (pronounced ip-ee-LIM-yoo-mab), when combined with dacarbazine, extended median survival to 11.2 months compared with 9.1 months for those who received dacarbazine alone. After three years, 20.8 percent of those who got that new drug were alive, compared with 12.2 percent of those in the control group.

The results of both trials were published online by The New England Journal of Medicine in addition to being presented here.

To be sure, more than half of patients with metastatic melanoma would not be helped all that much by either drug. Experts say more needs to be done, especially since melanoma affects more young adults than many other types of cancer.

Even if the new drugs allow patients with metastatic melanoma to live two years, “Two years is nothing when you’re 30,” said Dr. Anna C. Pavlick, head of the melanoma program at New York University.

Still, doctors and patient groups welcomed the progress because until now treatment of melanoma that had spread beyond the skin to distant organs “was terrible even by routine cancer standards,” said Dr. Vernon K. Sondak, chairman of cutaneous oncology at the Moffitt Cancer Center in Tampa, Fla.

Also, the number of melanoma cases has been rising, unlike for many other types of cancer. Doctors say that is because of unprotected sun exposure years ago, the proliferation of tanning salons and perhaps more attention to detecting the disease.

There were about 68,000 new cases of melanoma and about 8,700 deaths last year in the United States, up from 48,000 cases and 7,700 deaths in 2000, according to the American Cancer Society. Particularly fast increases have occurred among people older than 65 and among women 15 to 39 years old.

Vemurafenib is the latest so-called targeted therapy, which inhibits the effects of genetic mutations that spur tumor growth and spread. In particular, the drug counters the effect of a mutation in a gene called B-RAF that was discovered in 2002 to be common in melanomas. (The drug’s name comes from V600E mutation in RAF.)

The drug, which is taken orally twice a day, would be used only by the roughly half of melanoma patients whose tumors have this mutation. The drug significantly shrinks tumors in about half of these patients — or about a quarter of all melanoma patients.

It was developed by Roche and Plexxikon, a biotechnology company in Berkeley, Calif., that was recently acquired by Daiichi Sankyo of Japan. The drug is expected to be approved by the Food and Drug Administration within a few months.

Ipilimumab, the other new drug, releases a brake on the body’s immune system, allowing it to more effectively attack the tumor. Developed by Bristol-Myers Squibb, it was approved in March and is sold under the name Yervoy.

A series of articles in The New York Times last year followed the development of vemurafenib, then known as PLX4032, and recounted how some patients close to death seemed to make miraculous recoveries.

The effect, however, typically lasts only about seven months before the cancer starts to grow again, though some patients benefit for more than two years.

S. Taylor Chance, a 67-year-old real estate agent in Rancho Cucamonga, Calif., has been taking vemurafenib in a clinical trial since March 2010. “If it weren’t for the trial I wouldn’t be here,” she said.

It has not been all good. Ms. Chance said the drug caused such extreme pain at one point that “I called in the children and said, ‘I’m done, I can’t do this any more.’?” But she had her dose reduced and took other medications for the pain.

In the trial, sponsored by Roche and led by Dr. Paul B. Chapman of the Memorial Sloan-Kettering Cancer Center in New York, 38 percent of participants had to stop taking the drug or lower the dose because of side effects, including rash and joint pain. Many patients get minor skin cancers that can be removed by dermatologists.

The trial of ipilimumab, paid for by Bristol-Myers, involved 502 patients with late-stage melanoma.

Last year at this conference, researchers presented results of a trial showing a survival advantage for patients who had undergone a previous treatment. The new trial of this drug, by contrast, involved patients who were getting treated for the first time.

While the extension of median survival of two months, from about 9 months to about 11 months, was less than some experts expected, researchers said the real benefit was that a small number of patients, perhaps 10 to 20 percent, could live a long time.

Because it unleashes the immune system, ipilimumab can have serious side effects. In the latest trial, a big one was liver damage.

A course of treatment of ipilimumab costs $120,000. The price of vemurafenib has not been announced, but is expected to be at least tens of thousands of dollars per year.

Doctors are eager to try the two drugs together. Roche and Bristol-Myers said Thursday that they would conduct such tests.

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Mexico drugs shoot-out kills 13

 10 May 2011 Last updated at 07:05 ET  The drugs cartel camp was on an island in Falcon Lake Mexican marines have killed at least 12 suspected members of the Zeta drugs cartel after stumbling upon a camp at a lake on the Mexico-US border.

A soldier was also killed in the gunbattle on Sunday.

The camp was on an island in Falcon Lake, a dammed section of the Rio Grande, in the north-eastern state of Tamaulipas.

The authorities believe the gang used the base for smuggling marijuana into the United States by speedboat.

Turf war

The Mexican navy said the gunmen opened fire first, when a marine patrol discovered their encampment.

The authorities seized more than 20 guns after the shootout, including several assault rifles.

Falcon Lake is where the American citizen David Hartley is thought to have been chased and gunned down last September. His body has not been found and Mexican investigators have reported no progress in the case.

The Zetas are locked in a fierce turf war with the Gulf cartel that has turned much of Tamaulipas state into a virtual war zone.

Last month security forces discovered more than 40 graves containing 183 bodies. Many of the victims had apparently been pulled off passenger buses by Zetas gunmen trying to recruit them.

Drugs in Ozarks Town Infect Even Sheriff’s Dept.

For two troubled years, Mr. Adams was sheriff of Carter County, until his arrest last month on charges of distributing methamphetamine, the home-brewed drug that has poisoned much of this poor, sparsely populated stretch of timber country. Mr. Adams was accused of regularly snorting it as well.

But in this long-struggling community in southeastern Missouri where distrust of law enforcement has always run deep, the story of a sheriff enabling the scourge he was supposed to fight has not provoked outrage. Rather, many local residents are accepting it, even sympathetically, as another disappointing chapter in what they see as a hopeless fight.

“It shows how entrenched methamphetamine is in our system,” said Rocky Kingree, the county prosecuting attorney. “It’s something that has to be stopped, and it doesn’t seem like there is an end in sight.”

For most of a decade, Missouri has led the nation by a wide margin in the number of labs discovered to be producing methamphetamine, a highly addictive stimulant that can be made with household products like nasal decongestants. And throughout the Ozarks, the drug has metastasized.

In Ellsinore, the creeping problem has strained the bonds of its 446 residents. People recognize the symptoms of use in neighbors but, reflecting a culture of fierce independence, say nothing.

“We all know who does what, how they do it and when they do it,” said David Bowman, a school maintenance worker who is the mayor of Ellsinore. “You just turn your head and go on.”

In a community where hunting is less a hobby than another way to put food on the table, Mr. Adams was one of the many local boys who learned to string together a living out of odd jobs, working as a fry cook, an auto mechanic and the town’s one-man, part-time police force.

Three years ago, Mr. Adams, who is now 31, ran against the two-term sheriff, Greg Melton. There were persistent rumors about Sheriff Melton, including that he used methamphetamine. Several residents said last month that he had stolen from them or had sold them stolen goods.

Less than a month before the election, Mr. Melton was found dead in his garage, shot through the head. The county coroner, who found a gun in Mr. Melton’s hand, said that despite rumors otherwise, there was no doubt he had killed himself.

Mr. Adams’s narrow victory put him in charge of three deputies and a 500-square-mile region with 6,265 residents. Keeping a lower profile than his predecessor, he quickly became the subject of rumor himself. He rarely met with community leaders or showed up at the office, where paperwork piled high on his desk. He delegated to his chief deputy, who worried about his strange behavior.

Mr. Adams began spending conspicuously, buying cars, building a cabin and paying for the in vitro fertilization that led to the birth, eight months ago, of his son.

Like many people around here, he had grown up poor. He declared bankruptcy in 2005, with just $5 in cash and $300 in the bank. And even though his new $37,000 salary, on top of his wife’s pay as a nurse, represented good money in an area where the median household income is $27,000, his spending raised eyebrows.

Then there were his friends, including Richard Kearbey, who was arrested years earlier on charges of trying to buy 50 pounds of methamphetamine.

Though a federal judge in a later case described him as “the ringleader of a fairly large methamphetamine distribution network,” Mr. Kearbey served just seven days in jail. Instead, he worked as an undercover informant, helping arrest a number of small-time meth cooks, according to federal court records. (Neither Mr. Kearbey nor his longtime lawyer responded to messages seeking comment.)

 

Drugs in Ozarks Town Infect Even Sheriff’s Dept.

For two troubled years, Mr. Adams was sheriff of Carter County, until his arrest last month on charges of distributing methamphetamine, the home-brewed drug that has poisoned much of this poor, sparsely populated stretch of timber country. Mr. Adams was accused of regularly snorting it as well.

But in this long-struggling community in southeastern Missouri where distrust of law enforcement has always run deep, the story of a sheriff enabling the scourge he was supposed to fight has not provoked outrage. Rather, many local residents are accepting it, even sympathetically, as another disappointing chapter in what they see as a hopeless fight.

“It shows how entrenched methamphetamine is in our system,” said Rocky Kingree, the county prosecuting attorney. “It’s something that has to be stopped, and it doesn’t seem like there is an end in sight.”

For most of a decade, Missouri has led the nation by a wide margin in the number of labs discovered to be producing methamphetamine, a highly addictive stimulant that can be made with household products like nasal decongestants. And throughout the Ozarks, the drug has metastasized.

In Ellsinore, the creeping problem has strained the bonds of its 446 residents. People recognize the symptoms of use in neighbors but, reflecting a culture of fierce independence, say nothing.

“We all know who does what, how they do it and when they do it,” said David Bowman, a school maintenance worker who is the mayor of Ellsinore. “You just turn your head and go on.”

In a community where hunting is less a hobby than another way to put food on the table, Mr. Adams was one of the many local boys who learned to string together a living out of odd jobs, working as a fry cook, an auto mechanic and the town’s one-man, part-time police force.

Three years ago, Mr. Adams, who is now 31, ran against the two-term sheriff, Greg Melton. There were persistent rumors about Sheriff Melton, including that he used methamphetamine. Several residents said last month that he had stolen from them or had sold them stolen goods.

Less than a month before the election, Mr. Melton was found dead in his garage, shot through the head. The county coroner, who found a gun in Mr. Melton’s hand, said that despite rumors otherwise, there was no doubt he had killed himself.

Mr. Adams’s narrow victory put him in charge of three deputies and a 500-square-mile region with 6,265 residents. Keeping a lower profile than his predecessor, he quickly became the subject of rumor himself. He rarely met with community leaders or showed up at the office, where paperwork piled high on his desk. He delegated to his chief deputy, who worried about his strange behavior.

Mr. Adams began spending conspicuously, buying cars, building a cabin and paying for the in vitro fertilization that led to the birth, eight months ago, of his son.

Like many people around here, he had grown up poor. He declared bankruptcy in 2005, with just $5 in cash and $300 in the bank. And even though his new $37,000 salary, on top of his wife’s pay as a nurse, represented good money in an area where the median household income is $27,000, his spending raised eyebrows.

Then there were his friends, including Richard Kearbey, who was arrested years earlier on charges of trying to buy 50 pounds of methamphetamine.

Though a federal judge in a later case described him as “the ringleader of a fairly large methamphetamine distribution network,” Mr. Kearbey served just seven days in jail. Instead, he worked as an undercover informant, helping arrest a number of small-time meth cooks, according to federal court records. (Neither Mr. Kearbey nor his longtime lawyer responded to messages seeking comment.)

 

As Generics Near, Makers Tweak Erectile Drugs

Levitra, another erectile dysfunction drug, is now sold as a dissolvable tablet in nine European countries and may come to American pharmacies as soon as this month under the name Staxyn. That new form of the drug, which fizzes and dissolves in seconds, is marketed in a pocket-size, midnight-black box for men who prefer to take it discreetly, without water.

The third drug for erectile dysfunction to reach the market, Cialis, now eight years old, is racing ahead of the others because of two ideas that have proven extremely popular: an everyday pill and a 36-hour “weekender.” Cialis is projected to become the top-selling of the three drugs in the world this year, passing Viagra.

The market for drugs to correct erectile dysfunction has passed $5 billion a year from sales to tens of millions of men. And it is increasingly being driven by novel applications to compete with the lower-priced generics on the horizon.

“?‘Gimmick’ is a strong word, but all of this is designed to create new brand identities,” Dr. Joseph P. Alukal, an assistant professor and director of reproductive health at the New York University School of Medicine, said. “A newer product, less expensive, and a new form of taking it — all that might convince more people to try it.”

Research is also under way in Brazil on a faster-acting form of the drugs, which increase blood flow by relaxing smooth muscle cells. While the existing pills enter the bloodstream indirectly by way of the stomach, intestines and liver, this form would enter more directly, dissolving in a capillary-rich space under the tongue and increasing the blood flow within 10 or 15 minutes. The research in Brazil involves generic Viagra, but Pfizer says it is not sponsoring the work.

The Mexican experiment with Viagra Jet will show whether the chewable form of the drug has promise in other countries, particularly developing markets, Susan O’Connor, Pfizer’s vice president of global commercial development, said in an interview. Studies showed most Mexican men who used Viagra ground it up to make it easier to swallow or in the belief it would start acting faster.

In explaining why the drug is being test-marketed in Mexico, Ms. O’Connor cited “patient preference, found in market research.” Mexico is the biggest market for Viagra in the developing world, with about $55 million in sales last year. At this point, Pfizer does not have plans to bring Viagra Jet to the United States, she said.

In America, Pfizer is battling to keep low-price generic competition off the shelves a year from now, when the drug’s patent expires. The generic pills would cost only a fraction of the $10 or more that each pill now costs.

Bayer, meanwhile, has introduced the dissolvable form of its Levitra drug in Austria, France, Hungary, Germany, Spain, Poland, Sweden, Denmark and Britain, where it went on sale in late March. The drug is called Levitra ODT, for orodispersible tablets. It comes in a thin black package the size of a half-dozen stacked credit cards, with four pills on a card that slides out.

“It’s pocket-friendly, discreet and gives the product a playful edge over its competitors,” Thomas Proske, global brand manager for Levitra at Bayer Healthcare, said in a statement.

The same pill was approved in the United States last June under the brand name Staxyn.

It will be available in pharmacies this month, according to Jess Macnaught, marketing executive with Burgopak Design and Packaging, the London company that designed the new black package. GlaxoSmithKline and Merck have licensed American rights from Bayer, but they declined to reveal when the drug would be introduced. Last year, they said Staxyn would reach the market in late 2010.

Worldwide sales of erectile dysfunction drugs grew 6.9 percent in 2010, to about $5 billion, and 4.7 percent in 2009, according to the industry data firm IMS Health.

Dr. Alukal of New York University said he thought Staxyn could be sold for a much lower price than what Levitra and other pills now cost, in part to compete with a generic Viagra. No price has been revealed.

“I guess it could be easier to ingest, so it could expand its market somewhat, but in the end the bigger issue would be cost,” Dr. Alukal said. He said the companies, for whom he does not consult, had talked about lower pricing, perhaps to under $10 a pill.

But for now, Pfizer, the company that started it all, is focusing its attention on protecting the pricing power and brand integrity of Viagra.

Patrick Ford, a former F.B.I. agent who leads the company’s security operations in the Americas, says Viagra is the most counterfeited product in the world. His agents pose as buyers, collect evidence and bring fraud cases to prosecutors, and he says fake Viagra may be unsafe. Pfizer and other pharmaceutical companies are working with Victoria Angelica Espinel, the government’s intellectual property enforcement coordinator, a position President Obama appointed her to in 2009.

Pfizer is also using its legal firepower against would-be generic competitors. Pfizer has two patents for Viagra, one for its chemical, expiring in 2012, and the other for its use against impotence, expiring in 2019. Pfizer sued Teva Pharmaceutical Industries, the biggest generic-drug company, in March 2010 under the “use” patent. The suit is pending in a Virginia federal court.

MacKay Jimeson, a Pfizer spokesman, said the company was confident it would keep the 2019 patent protection, but industry analysts disagree.

“?‘Use’ patents are not highly probable of being upheld in court,” said C. Anthony Butler, a Barclays Capital pharmaceuticals analyst. “Most if not all analysts assume the expiry of the drug upon expiry of the composition of matter patent.”

The chemical patent expires on March 27, 2012. Pfizer may be able to extend it another six months, to September 2012, under a federal law called the Best Pharmaceuticals for Children Act. The law is meant to encourage drug companies to study children’s uses, often a difficult and unprofitable area.

In this case, what would be studied is not Viagra for children, but Revatio, a formulation of the same chemical, sildenafil, which is approved for pulmonary arterial hypertension, a rare and dangerous condition affecting hundreds of children in the United States. Mr. Jimeson said the company was working closely with the Food and Drug Administration to discuss the pediatric studies of Revatio and the potential for an extension on the chemical patent, which would also protect Viagra and its prices.

Many men, though, have waited years for a lower-priced Viagra and their wish may come true next year.

Other researchers are testing new uses for Viagra that Pfizer says it is not financing. Boston University is studying it with testosterone gel in men 40 to 70. Laboratório Teuto Brasileiro, in Brazil, where the patent expired last year, has filed a notice of intent to test it in a tablet that dissolves under the tongue and has an effect in 10 minutes or so. Pfizer owns 40 percent of the lab but says that it did not initiate the study.

Eli Lilly, meanwhile, says it has no plans to try chewable or dissolvable or any other forms of its Cialis tablets, and why should it? Cialis sales have steadily increased since it was introduced in 2003, to $1.7 billion last year, close to Viagra’s $1.9 billion. The health care investment house Leerink Swann estimates that Cialis sales will edge past Viagra in 2011 and far surpass the iconic blue pill in 2012.

Shawn Heffern, Lilly’s United States marketing director for Cialis, says, “I couldn’t be more happy.”