Angiogenesis Inhibitors: The Future of Cancer Treatment
There is a race heating up between the laboratories of several biotechnology companies today, the implications of which are enormous from a health care perspective and even larger on the corporate financial front.
The race is to develop a new class of compounds, called angiogenesis inhibitors, which treat cancer in an entirely different way than conventional chemotherapy. This novel approach to the treatment of cancer was first theorized almost 20 years ago, but it has been only in the last five years that the theory has been transformed into impressive laboratory results that have excited the scientific, media, and corporate communities.
The competitors in this race range from small, unprofitable biotechnology companies to the giants of the industry. The stakes are high and in the next two years a winner will emerge. But before talking about these companies, let’s take a look at this new medical technology and why it’s so important.
What is Tumor angiogenesis?
| The transformation of a normal cell into a cancer cell is very different for many types of cancers |
Tumor angiogenesis, a theory supported by Dr. Folkman for over 20 years, has finally come of age. All tumors, as they develop, need a blood supply to nourish their rabid growth. Cancer cells relish the nutrients that human blood has to offer and have developed a complex way of inducing the formation of new blood vessels as they grow. This process, called angiogenesis, involves a series of signals and pathways in the body that have only become fully understood in the last several years. Now that this process has been understood and broken down into its components, it is currently the hottest area of cancer treatment research today.
Why is tumor angiogenesis Important?
This is the question that, I believe, will have an answer worth billions of dollars. Angiogenesis is a normal process in the human body, and–this is the key fact–it also is a process common to all cancers. As I mentioned, all cancers are not alike, and treatment for one cancer may be useless for another. Even when an effective treatment is discovered for one type of cancer, some patients’ tumors will become resistant to treatment. This has been a persistent problem without a viable solution.
| A Boston scientist named Dr. Judah Folkman originally brought to light a common thread to all cancers |
Tumor angiogenesis inhibitors: The Facts and the Future
Tumor angiogenesis inhibitors were introduced to the world in May 1998 with the help of the New York Times. A feature article describing the work of Dr. Folkman and his two angiogenesis inhibitors, angiostatin and endostatin, introduced the enormous potential of this new class of compounds.
The article was just an aftershock in the scientific community since Dr. Folkman’s work was already known. However, the effect on Wall Street was that of an earthquake, and the small company working with Dr. Folkman was at the epicenter. Entremed Inc., an obscure, unprofitable biotechnology firm was obscure no more. Its stock quadrupled in one day on the article’s reporting of stunning laboratory results of angiostatin and endostatin. Entremed shot from $10 well above $50 after the Times article hit the newsstand. Since then, it has returned to earth some with trading in the $20-$30 range. Was this an overreaction or was this a reaction to an exciting new class of anticancer compounds with enormous potential?
| Angiogenesis involves a series of signals and pathways in the body that have only become fully understood in the last several years. It is currently the hottest area of cancer treatment research today. |
Angiogenesis inhibitors have several advantages over existing cancer treatments: They can work on a broad spectrum of tumors, unlike many treatments today; they are also not toxic to normal cells, like conventional chemotherapy, and they do not produce hair loss, gut-wrenching nausea, or mouth sores. With this new class of compounds, cancer cells cannot become resistant to treatment. All this adds up to incredible benefits to mankind and to potentially incredible profits for the companies that make it to the finish line.
New developments
Currently there are a dozen companies testing inhibitor compounds in human trials today against a variety of cancers. Below are some new developments:
- researchers at Duke University have recently identified the site on blood vessel cells where angiostatin attaches to does its work. Angiostatin is a bulky molecule and if the small binding site, or receptor, can be deciphered then a smaller compound potentially can be developed to snugly fit into this site. The smaller a compound is, the easier it is to mass produce, especially in pill form.
- researchers in Boston, in association with the company Boston Life Sciences, have identified an angiogenesis inhibitor in human cartilage (found in all joints in the body). Testing is underway in animals to evaluate its anticancer effectiveness.
- Dr. Folkman’s lab and Entremed have shown that endostatin can reduce the formation of arteriosclerotic plaque by 85% in mice. The implications of this to treat heart disease and expand the market for these compounds increases the stakes.
The companies
Entremed Inc. [END>END] This small Rockville, Maryland-based biotech company burst onto the scene as a result of the NY Times article in May, 1998. After this article and the surge in Entremed’s stock, the entire world was fascinated by the angiogenesis inhibitors endostatin and angiostatin. Entremed is in the business of developing drugs which block a tumor’s ability to induce the formation of blood vessels. The company currently has no products on the market and since the Times article, its stock price has been on a roller coaster ride.
| Entremed shot from $10 well above $50 after the NY Times article hit the newsstand |
Currently Entremed has a market capitalization of $306 million and has been trading in the $20-$25 range. It has been as high as 36 in the last year. It is not profitable and does not plan on having any products on the market for several years. While it is the pioneer company in the field of tumor angiogenesis inhibitors, there are other companies further along in clinical trials.
Sugen Inc. [SUGN>SUGN] Sugen is a San Francisco-based company involved in developing drugs to fight a variety of cancers, including angiogenesis inhibitors. The company is nurturing many anticancer agents and has an impressive evolving pipeline. Several of these drugs are in phase II and III clinical human trials.
Sugen’s most promising angiogenesis inhibitor is a compound called SU5416, which is about to enter phase III clinical trials against colon and lung cancer. This drug blocks Vascular Endothelial Growth Factor (VEGF), a key protein that triggers the growth of new blood vessels in the majority of solid organ tumors. VEGF is important because it is common to many cancers and this drug could potentially have a broad appeal. Sugen is also developing drugs to treat such large-market diseases as diabetes, rheumatoid arthritis, and cardiovascular disease.
The company was recently bought by Pharmacia & Upjohn in a stock deal valued at $650 million. It currently has a market capitalization of $512 million. It is not profitable and expects to lose $2.52/share in 1999 according to first call (it lost $2.53/share in 1998). It has traded as low as $9/share and as high as $30/share.
Sugen has a good pipeline of anticancer agents, and, with the pockets of Pharmacia and Upjohn, should have the financial backing to develop many of these drugs. It is also ahead of Entremed in the angiogenesis inhibitor race with phase III trial results potentially due out next year.
The rest of the pack
Besides Entremed and Sugen, several other companies are actively developing tumor angiogenesis inhibitor drugs. TAP Holdings Inc., a joint venture between Abbott Labs and Takeda Chemical Industries Ltd., is developing a drug (TNP470) which has shown promising results in mice against a variety of tumors. It is currently conducting phase II/III clinical trials against a wide spectrum of cancers in adults and children.
Genentech [GNE>GNE], the San Francisco-based biotech giant, is nurturing an anti-VEGF antibody angiogenesis inhibitor. It is currently testing this drug against a variety of human cancers in phase II/III clinical trials. This compound so far has shown great promise and potentially could add to Genentech’s growing stable of genetically derived drugs.
Agouron Pharmaceuticals and Novartis are also in the tumor angiogenesis inhibitor business. Agouron, recently bought by Warner-Lambert [WLA>WLA], has a drug in the late stages of human trials to treat lung and prostate cancer. Novartis also has a drug in the early phases of human trials that blocks a tumor’s ability to induce blood vessel growth.
The final word
Tumor angiogenesis is an exciting, new area of cancer research. The concept is simple: kill cancer cells by choking off their blood supply. Many companies are investing large amounts money and energy to develop drugs that do just that because the market and appeal for these drugs is huge.
Will these drugs be the magic bullets to cure cancer? I do not think so. However, once fully developed they will play a significant role in the war on cancer. Which company will get there first? This is currently the unanswered question. Entremed brought everyone to the dance, but companies like Sugen and Genentech are taking the lead in potentially bringing the angiogenesis inhibitors to market. I believe we will have an answer within the next two years given the rapid pace of research.