New Weapons Are Poised to Win the Battle Against Cancer

For people of any age, the word “cancer” has carried dire connotations for generations. Until recently, that ominous sense of cancer as a killer was literally true, at least for many forms of the disease. And just 10 years ago, there were few treatments apart from the crude and devastating ones, such as chemotherapy and radiation.

But two important developments have changed that and today, according to a recent Associated Press report, we are on the brink of a revolution in the treatment of cancer. This will literally make cancer just another serious, but treatable, class of diseases.

Of the two biggest trends that have changed what’s going on in cancer research, one is scientific, and the other is financial. On the scientific front, finding treatments has become far more likely since researchers have mapped the human genome. In addition, other advances in biotechnology have pushed the limits of what medical science can do to detect and kill cancer cells.

On the financial front, more and more pharmaceutical and biotech companies have come to realize that any new cancer treatment is going to command a very high price and generate substantial revenue, since there is little competition in the field ? so far. Any company that can stake a claim for actually curing a certain type of cancer is expected to have a long and lucrative run on its patent life. As a result, firms have poured billions into discovering the next blockbuster.

Some companies, such as Bristol-Myers Squibb, and AstraZeneca have long been involved in cancer research. Others, like Wyeth, Schering-Plough, GlaxoSmithKline, and Merck are more recent entrants in the “gold rush” for new treatments. Many have purchased smaller drug companies that are working on cancer cures. Others have licensing arrangements with them or have created their own specialized skunk works to investigate new therapies.

A prime example of this is Wyeth. A little more than two years ago, it created a research institution in Cambridge, Massachusetts aimed at the study of cancer and treatments for it. With this research facility, Wyeth scientists, freed from the corporate parent, can work at a faster pace and can collaborate with the rich academic community in the Boston area. Wyeth has 13 drugs in clinical development for the treatment of cancer, three times as many as the company had before establishing its new labs.

GlaxoSmithKline is another example. The company, created in 2000, represents two merged drug firms that had separately developed two drugs for cancer. Since then, it has created six more drugs, as well as three others for treating side effects, one preventive vaccine, and three therapeutic vaccines.

Pfizer is now spending more on cancer research than for almost any other drug quest. It has developed a drug that will compete with Gleevec, the most popular cancer drug on the market, and will soon file for FDA approval.

The main reason so many big companies are rushing to develop cancer drugs and get them approved is that the potential payoff is huge and, for the first time, the technology is there to create workable new therapies. For example Novartis introduced Gleevec in 2001 for the treatment of leukemia as well as for gastrointestinal tumors. It costs almost $2,500 a month for each patient, and despite the high price tag, Novartis generated $1.6 billion in revenues from the drug last year alone. Pfizer’s new entry could bring in $1 billion.

Despite the fact that insurance covers some ? or even most ? of the cost, the staggering prices are causing controversy. Erbitux is a drug that was introduced last year by Bristol-Myers and ImClone Systems. It costs up to $40,000 every month as a treatment for colorectal cancer. The primary driver behind the high price is that the cost of developing such a drug can approach $1 billion.

But, going forward, the very technology trends that are enabling the creation of such drugs for the first time may also help reduce their up-front cost. This is especially important because there are so many different types of cancer, each requiring a unique treatment, and often there aren’t that many people who get any particular kind of cancer. In other words, it’s not like developing a drug for high blood pressure, or even diabetes, where the development costs can be recovered through treatments for millions of people.

The technologies that will contribute to lower development costs involve a number of hot areas related to biotech, including genetic engineering and nanotechnology. For example, reengineering human proteins has led to molecules that can change what would have been a certain “death sentence” five years ago into a “virtually normal life.”

A tiny company called Sugen recently engineered such a drug ? named Sutent ? to treat kidney cancer. Sutent can eliminate all traces of the cancer with only minor side effects. Sugen was bought by Pfizer in 2002, and Sutent will probably be approved soon for the treatment of stomach cancer.

Another crucial technology trend involves scanning cancer cells and finding specific mutations that give hints about what chemicals could disrupt a particular cancer. That kind of information used to take between five and 10 years to develop. But now, according to a June 13, 2005 cover story in BusinessWeek, scientists can use the technology to bring a new drug into clinical trials in just two to five years.

There are now 230 such new drugs that have come on the market through biotechnology. Last year 20 more were approved, including some for cancer. Some four dozen more are expected to be approved in the next year, and these new types of treatments are winning approval at a much faster rate than traditionally developed medicines. As a result of these new technologies, some scientists are starting to refer to this as the Golden Age of Drug Discovery.

But this Golden Age was not the creation of the major pharmaceutical companies. On the contrary, Big Pharma more or less ignored the new technologies, until recently. It was the academic, clinical researchers who saw the potential of biotech and pushed it for decades, with little outside help.

For example, Erbitux was pioneered by Dr. John Mendelsohn, president of the University of Texas M.D. Anderson Cancer Center. For more than 30 years, Mendelsohn researched how growth factors regulate the proliferation of cancer cells by activating receptors on the surface of cells that control key cell signaling pathways. He developed specific monoclonal antibodies that block these receptors, thereby preventing growth factors from stimulating cell division.

His research led to clinical trials that are evaluating the role of combining a targeted monoclonal antibody, which he discovered in 1983, with chemotherapy or radiation for patients with several forms of cancer. After decades of searching, he finally found a company, ImClone Systems, willing to undertake the new treatment ? and Erbitux is the result.

Similarly, Gleevec, the most effective cancer drug of the past decade, was almost abandoned by Novartis. If Dr. Brian J. Druker, a cancer specialist from Oregon Health & Science University, hadn’t championed the treatment, the drug might never have reached the market ? and the thousands of grateful patients now taking it might have died.

Today, the major pharmaceutical companies are scrambling to get back in the game by buying up companies like ImClone. But there is some catching up to do. Smaller biotech firms, not Big Pharma, produced 67 percent of the drugs that were in clinical trials last year. Significantly, they spent far less developing them ? about 3 percent of the $40 billion that Big Pharma spent on its research.

Part of the reason for this gap is that the major drug companies have been following a business model that was based on the “blockbuster drug.” They would spend billions developing drugs in the hope that one would become the next Viagra or Valium or Vioxx. Meanwhile, the biotech firms, led by academic researchers, were looking for those areas that Big Pharma ignored so they could fill the unmet needs. Genentech started that way and now enjoys a market capitalization larger than Merck’s.

The nine new biotech drugs approved in 2004 will ring up $3 billion in revenues in 2005. That number is expected to grow to $8 billion by 2007, when the whole 1,500-company industry will finally become profitable.

Most of this success is due to cancer drugs, and targeting is the name of the game. Targeting is the concept of delivering the cancer-killing agent only to the cancer cells and leaving the rest of the body alone. Until now, that was only a dream. But with biotech ? and even nanotech ? it’s not only possible, it’s a reality. In 2004 alone, four targeted cancer drugs ? Avastin, Tarceva, Iressa, and Erbitux ? received FDA approval. Avastin, developed by Genentech, made history by extending survival rates in cases of lung, breast, and colon cancer.

There are now targeted drugs that can block growth factors that make tumors spread. There are drugs that can starve the tumor by inhibiting the growth of new blood vessels. Some combine radioactive isotopes with engineered proteins that can sense and move toward the tumor like a smart bomb. And most promising of all, there are vaccines that can direct the immune system to attack cancer cells.

Among this type of targeted treatments are ones involving the use of stem cells. According to the Journal of the National Cancer Institute, scientists at the University of Texas M.D. Anderson Cancer Center have developed a revolutionary technique for delivering anti-cancer drugs to the actual site of the tumor using specialized stem cells that repair the day-to-day wear and tear on the body.

It turns out that cancer acts like a wound that never heals, calling upon these cells to help build up supporting tissue for the tumors. By loading the stem cells with a highly toxic anti-cancer drug called interferon beta, they can use the cancer’s own tricks to kill it.

The fact that the tumor’s own supporting structure sends out signals to attract the booby-trapped stem cells means that even a previously untreatable cancer that has spread throughout the body can be attacked by this method.

Another hot development in this area is called multi-targeted drugs. Sutent, one of these so-called multi-kinase inhibitors, is being used against kidney cancer. Multi-kinase inhibitors block the proteins that circulate in the bloodstream and assist tumors in growth and in the creation of new blood vessels.

Sorafenib is another kidney cancer drug of this class that was developed by Bayer and Onyx Pharmaceuticals. Similarly, Lapatinib, from GlaxoSmithKline, is aimed at breast cancer. Both are expected to be approved by the FDA next year, or even sooner.

These multi-targeted therapies offer hope to even the sickest patients. Consider glioblastoma, a type of brain cancer that attacks the glial cells that bind neurons together. It is almost always fatal, and once diagnosed, patients often have but a few months to live.

Eli Lilly has developed a multi-targeted drug called Enzastaurin that blocks cell growth and the creation of new blood vessels, but only in the cancer itself, not in the rest of the brain. This has so far resulted in a 25 percent success rate in trials. But as the technique is refined, Enzastaurin may be able to cure what has, until now, been an extremely lethal form of cancer.

One of the biggest problems with cancer is discovering it early enough to have any hope of treatment. This brings us to another area that biotech is addressing: diagnostics. By combining biological agents with intelligent technology, companies such as Roche have come up with so-called “DNA chips” that can potentially not only tell if someone has cancer, but also what type it is, and what drugs will help. Some of these genetic analyzers, which use only a drop of blood, are already approved and in use.

One reason that diagnostics is becoming even more important is that cancer is, in effect, a custom-designed disease. That is, every human body creates cancer differently, and therefore no two are exactly alike. That means that there may be a very effective cancer drug that will work on only a small percentage of cases, such as 10 to 25 percent of the people who have a particular disease. If you can do a quick genetic test on such patients, you can tell who will, and who will not, respond to a given drug.

Recognizing this, Genentech introduced a drug, Herceptin, and a genetic test for its effectiveness at the same time. Introduced in 1998 for the treatment of breast cancer, it was the first drug to be marketed with its own genetic test. Abbott Labs is following suit with developing genetic testing for AstraZeneca’s Iressa and Bristol-Myers Squibb’s Erbitux ? drugs that have proven to be highly effective, but only in 10 to 25 percent of patients.

The next obvious step, of course, is to test people preemptively to see who is susceptible to getting various types of cancer and to treat them before the symptoms appear. Myriad Genetics is doing just that by developing tests to predict the likelihood that an individual will get breast cancer, colon cancer, or melanoma.

In light of these promising trends, we offer the following six forecasts for your consideration:

First, in the two-to-five-year range, large segments of the population that previously would have died from various forms of cancer will find effective treatment. They are already doing so in many cases. And the widespread use of novel therapies will continue to erode the toll that cancer exacts in morbidity and mortality throughout the world.

Second, in the five-to-10-year time frame, the cost of these therapies will gradually fall so that they can reach patients throughout the developed world. This will happen thanks to novel technologies and economies of scale brought on by the marriage of Big Pharma and “small biotech.” As development costs plummet, and the enormous cost of developing the underlying technologies are amortized, today’s high prices will become a thing of the past.

Third, within the next 15 years, targeted and multi-targeted therapies that perform much like multiple-warhead missiles will be perfected. These complex sets of diagnostics tools and treatments will be capable of seeking out and finding the cancer, diagnosing its genetic profile, and targeting it with one or more therapies to kill the cancer cells, while leaving healthy tissue undamaged. This will prove to be the most effective cancer therapy in history, curing most common cancers completely.

Fourth, by around 2020, as those technologies develop, children will be genetically profiled in the same way they are now given vaccines for measles. Early in life, a determination will be made of whether or not they’re susceptible to certain types of cancer. They will then be treated preemptively; perhaps using implanted DNA chips, so that if and when the cancer develops, it will be automatically suppressed by the appropriate molecular mix synthesized by the chips. In a sense, such a therapy will act as an adjunct to the normal immune system and will perhaps enlist its help in killing cancer cells before they can spread and grow.

Fifth, starting within the next five years and continuing for at least a decade or two, a whole new marketplace for both investment and commercialization of these new technologies will emerge. This marketplace will result from the push from large drug companies, combined with the pull from small biotech firms. One of the boom markets for investors in the coming decade and beyond will be in this synergistic field of Big Pharma and biotech, as discussed in prior issues of Trends.

Sixth, a new generation ? those who are children today ? will grow up in a world where the word “cancer” will not evoke the fear that it does today. In fact, a diagnosis of diabetes will be more serious than many cases of cancer. Currently, cancer is the leading cause of death for people the world over. While some forms of cancer may still be deadly for the coming generation, many if not most, will become either curable, or at least treatable, chronic diseases.

References List :
1. The Associated Press, March 17, 2005, “Push for Cancer Treatments Intensifies,” by Theresa Agovino. ⓒ Copyright 2005 by The Associated Press. All rights reserved.2. BusinessWeek, June 13, 2005, “Biotech, Finally: Yes, the Business Remains Risky, but Medical Progress Is Stunning,” by Catherine Arnst, Arlene Weintraub, John Carey, Kerry Capell, and Michael Arndt. ⓒ Copyright 2005 by The McGraw-Hill Companies, Inc. All rights reserved.3. Journal of the National Cancer Institute, November 3, 2004, Vol. 96, No. 21, “Mesenchymal Stem Cells: Potential Precursors for Tumor Stroma and Targeted-Delivery Vehicles for Anticancer Agents,” by Matus Studeny, Frank C. Marini, Jennifer L. Dembinski, Claudia Zompetta, Maria Cabreira-Hansen, Benjamin Nebiyou Bekele, Richard E. Champlin and Michael Andreef. ⓒ Copyright 2004 by Oxford University Press. All rights reserved.