When examining the success rate of drug candidates for the treatment of cancer, numbers are not encouraging. Historical figures show that once such a candidate reaches clinical trials, it has a 5% chance to be approved compared to more than 10% for the overall pharma industry. One of the things that makes cancer so difficult to treat is the fact that cancer cells share so many characteristics and functions with normal cells. This makes developing treatments that specifically affect cancer cells but spare normal cells, very challenging. Throughout the years, there has been a positive trend from non-specific, highly toxic treatments such as chemotherapy and radiotherapy towards compounds which specifically target cancer cells. Drug industry has come a long way from the early mustard gas derivatives, which were the first chemotherapy treatments, towards targeted therapies such as small molecule inhibitors and monoclonal antibodies.
Antibodies are playing an increasing role in cancer therapy due to their unique ability to recognize and target cancer cells in a specific manner. Antibodies do not target cancer cells as a whole, but certain structural elements presented on these cells called Tumor associated antigens [TAA]. Such elements must be selectively present on cancer cells, and absent from normal cells. Dozens of TAAs have been recognized so far, serving as targets for many treatments. Such targets, which usually play a critical role in the disease onset and progression, include agents that facilitate growth, enable cell migration and stimulate formation of new blood vessels. Recognizing such targets is a crucial primary step in the long way of developing an antibody-based treatment for cancer, but success is far from granted, even after such a target is found and validated as a TAA. In fact, there are validated TAAs that have been well known for many years, but there is still no approved antibody targeting them.
The first dilemma in choosing a TAA is whether to go after the “traditional” TAAs, which have been known and examined for years by many research teams, or to investigate poorly studied targets, perhaps even totally new, unfamiliar targets. Both routes have their advantages and disadvantages. One of the biggest advantages in targeting a well-known TAA is reducing chance of failure, as the target has already been validated. The downside of such a strategy is a potentially crowded, competitive market. Just like any other field, competition is excellent for customers (patients) but very bad for vendors (drug companies). A good example for that might be Amgen’s (AMGN) Vectibix, an approved monoclonal antibody that targets the same TAA Imclone’s (IMCL) Erbitux, does. Both antibodies are approved for the treatment of colorectal cancer and compete in the same market segment. Targeting a less common TAA, bears higher levels of risk, but makes success much sweeter, since there is a long period of market dominance until competition catches up.