Replies to post #1441 on Biotech Values

[10nisman]

7:49AM EYET started with an Overweight at Morgan Stanley 35.05: Morgan Stanley initiates coverage of Eyetech Pharma with an Overweight rating and a $42 target; with Macugen, firm believes that the co possesses an exciting late-stage commercial opportunity with $1 bln plus peak sales potential; with solid Phase III data in hand, a strong commercial partner (Pfizer) targeting a large potential mkt, and retention of a large share of future potential profits from sales of Macugen (50% in the U.S.), firm believes that the stock represents a compelling investment opportunity.

[DewDiligence]

War on Cancer Is Being Oversold

[This cynical piece is from Genetic Engineering & biotechnology News (c/o genisi). #msg-2562313, a 2004 article from Fortune, makes a good companion read.]

http://www.genengnews.com/articles/chitem.aspx?aid=2179

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Overhyping Decline in Cancer Deaths Is
Leaving Promising Treatments Unexamined

Aug 1, 2007.
by Ralph W. Moss, Ph.D.

The number of cancer deaths in the U.S. declined by one-half of one percent between 2003 and 2004—and the world went wild. Soon after the announcement, on January 17, President Bush paid a rare visit to the NIH to bask in the reflected glory of this alleged turning point in the war on cancer.

“Progress is being made,” Bush intoned. He characterized this decline in cancer deaths as “the steepest drop ever recorded.” While technically true, this gave the misleading impression that the decrease in the number of deaths was both dramatic and precipitous. In fact, the number of cancer deaths had steadily risen for over 70 years after record keeping began—a point that is frequently overlooked. Furthermore, as the population steadily ages and the baby boom generation enters its years of peak cancer incidence, the annual death toll is likely to steadily increase.

Understand that the widely trumpeted decline in U.S. cancer deaths amounted to only a few thousand, a fraction of a percentage point of the toll that cancer takes every year. Yet scientists and politicians made a self-congratulatory mountain out of a statistical molehill. One can, of course, always select facts and figures to argue that progress is being made, but, in my opinion, despite billions of dollars in private and governmental investment, the war is, to say the least, not going well.

From an economic point of view, however, certain pharmaceutical companies are having great success marketing new products for cancer. Since 1949, when FDA approved poisonous Mustargen for the treatment of cancer, scores of new oncology drugs have been licensed.

After the war on cancer was formally launched in December 1971, the rate of innovation slowly began to accelerate. While there were few new FDA approvals for cancer drugs in the 1970s and early 1980s, there were seven new approvals in 1987, 16 in 1996, 21 in 1998, and 28 in 2006. Of course, the absolute number of approvals reveals nothing about the effectiveness of those drugs. Many of them were new indications for older formulations; some drugs have been approved half a dozen or more times on separate occasions for various uses.

…To be fair, there have also been certain notable milestones during this protracted campaign. There was justifiable optimism when the FDA gave approval in May 2001 to Gleevec, among the first of a new generation of targeted drugs that selectively attack certain cancer cells.

…these were elegant drugs, a far cry from the crude mustard-gas derivatives and antimetabolites that ushered in the golden age of chemotherapy. Yet most of the targeted drugs that followed have, so far, failed to live up to expectations. For a start, these are no magic bullets. Targeted drugs are not particularly effective when given alone. Even when given alongside standard chemotherapy, their benefit is often only modest.

I recently spoke to a man with stage IV colorectal cancer whose oncologist was recommending the standard regimen of oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) followed by a targeted drug, Avastin. The oncologist conveyed his enormous enthusiasm for this new drug. I pointed out that the results of Eastern Cooperative Oncology Group study E3200, published weeks earlier in the Journal of Clinical Oncology, told a more sobering story.

In this study, patients with metastatic colorectal cancer were treated with FOLFOX4, Avastin, or a combination of the two. For patients treated with Avastin alone, overall survival was 10.2 months; with FOLFOX4 alone, 10.8 months; and, when FOLFOX4 and Avastin were given in combination, survival was extended by an average of just eight weeks. Furthermore, these two extra months were hardly trouble free: the new drug was associated with increased hypertension, bleeding, and vomiting. Avastin has also been associated with intestinal perforations—an unanticipated side effect that can be fatal.

Meanwhile, as colorectal cancer specialist Leonard Saltz, M.D., of Memorial Sloan-Kettering Cancer Center, has pointed out, the cost of treating advanced colorectal cancer has skyrocketed from $500 per patient in 1999 to $250,000 today, largely due to the addition of these targeted drugs. “There is not enough money in the till to treat everyone,” Dr. Saltz has duly warned.

Changing Cancer Drug Development

In oncology today, new drugs are usually announced amid a carefully orchestrated media blitz involving scientists, company representatives, and politicians. There follows a surge of near-euphoria as the latest potential cure is rolled out for public consumption. But, as we have seen time and again, these drugs quickly turn out to have minimal efficacy in clinical practice.

This public excitement serves the interest of the drug companies, which reap billions of dollars in sales from each new agent. Doctors also profit in various ways, not least from the generous rebates paid by drug companies to physicians who purchase or prescribe certain drugs, as revealed recently in the New York Times.

The media also benefit: feel-good news improves ratings and thereby boosts advertising revenue. Various government bureaucrats and patient advocates benefit because the hope generated by the arrival of each of these new drugs makes their own tenure more secure. The people who profit least from this repetitive cycle are the patients, whose hopes may be inordinately raised—and then dashed—by exaggerated claims. They also, directly and indirectly, foot the bill.

…the current reliance on watertight product patents to recoup the high cost of R&D has discouraged the full investigation of other, nonpatentable agents. This lack could possibly be remedied by FDA’s woefully under-funded Orphan Drug program or by support from philanthropic organizations. At the moment, some promising agents are withering on the vine because of lack of interest by big pharma.

At best, we will continue to face a stalemate for the foreseeable future. Our greatest hope of victory lies in a fundamental reform of the way in which we presently fund and conduct the fight against this dreaded disease.
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[DewDiligence]

Revisiting What’s Wrong With the ‘War on Cancer’

[This cover story in today’s Boston Globe revisits the subject of a 2004 article in Fortune magazine that is being made into a book.]

http://www.boston.com/news/nation/articles/2007/12/02

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Critics Say Costly Cancer Drugs Do Little to Extend Lives

By Scott Allen
December 2, 2007

Despite optimistic claims by national leaders that America is finally turning the tide against cancer, a growing number of patient advocates and researchers say they are discouraged by continuing slow progress in the nation's 36-year war against the disease.

Many of the most anticipated new drugs have extended patients' lives by only a few months at great expense, they say, and researchers still don't understand what makes the disease spread - the cause of 90 percent of cancer deaths.

Although deaths from cancer have declined slightly since 2002, cancer specialists say that reflects earlier detection of the disease as well as lifestyle changes, such as quitting smoking, more than dramatic improvements in treatments. For many types of cancer, once the disease has spread, or metastasized, the patient's chance of long-term survival is not much better than when President Nixon declared "war" on the disease in 1971, triggering what is now a $69 billion federal investment in cancer research. A patient whose lung cancer has spread to other organs, for example, has a 3 percent chance of surviving five years after the original diagnosis.

With federal funding for cancer research frozen since 2003, critics say the pace of progress could slow even more as young researchers leave the field. This year, the disease is expected to kill 560,000 people, putting cancer on a pace to become the nation's number one killer in the next few years. Heart disease, the current leading cause of death, has become almost 50 percent less lethal since the early 1970s, thanks to breakthroughs such as artery-clearing stents and cholesterol-lowering drugs.

"I would have expected us to be doing a heck of a lot better based on the investment that we've made and based on the prevalence of the disease," said Kathy Giusti, founder of the Multiple Myeloma Research Foundation, an organization based in Connecticut and one of several groups pressing researchers to develop better medications more quickly. When she was diagnosed with multiple myeloma, a rare blood cancer, in 1996, she said, "the treatments they offered me were exactly the same ones they offered my grandfather when he had the disease."

Advocates acknowledge that treatment is improving for some cancers - four new medications have been approved for multiple myeloma alone in the past five years, in part thanks to Giusti's efforts, while drugs such as Herceptin have extended the lives of women with breast cancer. But that is not enough to ease the fears of the 1.4 million people who will learn this year that they have cancer. After cancer spreads from its original location, doctors can only delay the disease, not cure it.

Moreover, studies show that many patients are not sharing in the modest progress, including those who have less common cancers as well as people with limited access to healthcare. Black women with advanced breast cancer typically live no longer now than in 1988, while white women have seen their life expectancy after diagnosis grow from 20 to 27 months, according to a recent study. The researchers said the likely factor was poor access to the latest treatments.

"I have never been as worried about our nation's commitment to the war on cancer as I am today," said Nancy G. Brinker, a breast cancer survivor and founder of an advocacy group called Susan G. Komen for the Cure, in a speech to thousands of cancer specialists in Chicago in June. She called on researchers to come up with better medicines: "There is a Great Divide between discovery and delivery… when we celebrate as 'breakthroughs' treatments that cost $50,000 and that extend life, at most, a few months! This is progress?"

Ironically, the pessimism comes at a time when knowledge about cancer is exploding and when leaders of the National Cancer Institute and the American Cancer Society talk hopefully about a day when doctors can stop cancer without the toxic side effects of traditional radiation and chemotherapy treatment. In 2005, the National Cancer Institute's director then, Andrew C. von Eschenbach, was so encouraged he set a goal of eliminating cancer by 2015. [This is probably not a quote he wants to be remembered for.]

Today, leaders of both institutions are careful not to declare victory, but they see clear signs of improvement, such as the slight decline in deaths from cancer that began in 2003 and continued through 2004, the latest year for which data are available. With a record number of cancer drugs now undergoing human testing, cancer leaders say the future for cancer patients looks brighter than it has in years.

"The evidence is unmistakable: We are truly turning the tide in the cancer battle," declared John R. Seffrin, chief executive officer of the Cancer Society, in an October news release celebrating the declining death rate.

But critics of the war on cancer say they've heard such sunny rhetoric before, beginning in 1969 when a powerful coalition of doctors and scientists ran a full-page ad in The New York Times urging Nixon to "conquer cancer by America's 200th birthday." For decades, promising cancer treatments have fizzled and leaders have used sometimes-misleading statistics to make the case that the war is going well. The most-used measure of progress is the five-year survival rate - the percentage of patients who live five years from the date of diagnosis. But wider use of screening tests for some cancers has led to tumors being found earlier, increasing the years patients live with cancer on average - the "survival rate" - without actually extending their lives.

Americans "have heard the same song for a generation - that we're finally making progress against the disease, that we've turned the corner. And it doesn't jibe with what they see and experience in their own lives," said Clifton Leaf, a Hodgkin's disease survivor and former Fortune Magazine editor who is writing a book on the "dysfunctional" cancer research industry. "Their loved ones are dying." [The kernel of Leaf’s book can be seen in #msg-2562313.]

Leaf believes that researchers have created their own problems by avoiding the toughest issue in cancer. The National Cancer Institute doesn't track how much of its budget goes toward metastasis research, but Leaf found that only 0.5 percent of institute grant proposals have focused on metastasis since the war on cancer began. [This is an astonishing stat.]

Today, doctors have few medicines that can shrink large metastatic tumors, and, for most cancers, no reliable way to tell patients after cancer treatment that the disease will or won't come back as metastasis. The difference is profound: A patient who has localized colon cancer has a 90 percent chance of being alive in five years. But, if the cancer has spread to distant parts of his body, the five-year survival rate drops to 10 percent.

"People come out of cancer surgery feeling like time bombs" because they don't know whether the disease will return, said Bruce R. Zetter, chief scientific officer at Children's Hospital Boston, who specializes in the study of metastasis.

Danny Welch, a pathologist at the University of Alabama at Birmingham and president of the Metastasis Research Society, said the failure to control metastasis is a major reason that the death toll from cancer has not come down dramatically. He said metastasis researchers have struggled to get support, largely because the spread of cancer is so complex and expensive to study and the likelihood of success so uncertain. In the 1980s, Welch said, some senior cancer scientists openly discouraged research into metastasis, contending that focusing on early detection and treatment was more cost-effective.

Welch said, however, said he is encouraged by recent growth in the field: Membership in his society has grown from nine to 250 since 1998. In addition, his lab and others have begun to identify the genes that signal tumors to spread.

"You can say progress is not as good as it should be, but the public needs to know there has been progress," said Welch.

Dr. Judah Folkman of Children's Hospital Boston, who pioneered a new field of cancer medicine with his discovery that certain proteins can cut off the blood supply that tumors need to grow, said he understands why patients are frustrated. After all, it took 25 years from when he developed the first angiogenesis inhibitor until a drug company won federal approval for the first treatment in 2004.

"Americans are impatient," he said. "That's why we have so much progress."

Indeed, that impatience has spurred advocacy groups to invest more in research directly. Giusti's multiple myeloma group, for example, has created its own tissue bank to provide researchers across the country with samples of multiple myeloma, and an increasing number of patients are donating money earmarked specifically for metastasis studies. Komen for the Cure, meanwhile, recently announced plans to invest $600 million "to find wild ideas that will break the mold" in treatment.

Folkman, however, said there is no substitute for the funding from the National Cancer Institute that has fueled basic cancer research since the 1970s. The federal budget freeze since 2003 translates into a 12 percent reduction due to inflation, resulting in more research proposals being rejected. Consequently, Folkman said, young researchers are leaving the cancer field at a time when science needs their new ideas.

Folkman said cancer has repeatedly surprised scientists with its resilience and complexity. In his field, scientists had once hoped that blocking the action of a single key protein called VEGF might be enough to shut down tumors' blood supplies, but now realize there are at least six proteins that help tumors form blood vessels. As a result, drug companies are now developing angiogenesis inhibitor medicines that attack three or more of the proteins at once, increasing the odds of driving cancer into remission.

Still, Folkman said he's encouraged by what he has seen in human testing, including at least one case in which doctors successfully used angiogenesis inhibitors in a patient who doctors said was at high risk of metastasis. The patient is still metastasis-free several years after his physician had predicted.

"When people say there is no progress and they are all gloomy, I don't say anything," said Folkman. "I know about things in the lab that are exciting."

So far, cancer researchers have had difficulty turning promising ideas into treatments. Their drugs take longer to win federal approval than other medicines and are more than twice as likely to fail, according to a September report by the Tufts Center for the Study of Drug Development. The Tufts study found that 92 percent of proposed cancer drugs that reach human testing are abandoned before they win approval.

"It's the siren call of science," said Kenneth I. Kaitin, director of the Tufts drug development center. "The science of cancer drug development suggests that the cure is right around the corner and we can never quite get there."
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