Re: High Bcl-2 expression in melanoma. My understanding is that the Bcl-2 factor is found in a variety of cancers, including melanoma and breast cancer. The higher the level of this factor, the more likely that Genasense is able to get a positive response. Or, on the other end, if the Bcl-2 factor is present at lower levels, then the impact of Genasense in combination with decarbazine is reduced.
Obviously, the sample size is very small, particularly after subdividing the study. One worrisome part of the study is that it showed better results before the cancer had metastisized. The treatment seemed to work better in older patients (over 50 years), which is a good sign, since more cancers occur in older people.
Seems to me that Genta made a major mistake in not concentrating on data from patients with high Bcl-2 expression. In other words, they should be putting their efforts only to that population subset with the higher Bcl-2 expression. If you get statistically significant tests for the subset, you may get at least limited approval by FDA. Once approved for even a minor portion of the population at risk, the treatment could then be extended to other patients.
Attempting to get the broadest possible approval for the use of a new drug is desirable from the profit point of view, but it carries greater risk if the drug doesn't work well on certain groups. Several companies that I monitor have made this same error of judgment and paid for it. ISIS Pharmaceuticals, for example, tried initially to get positive results from its antisense drugs used without any other chemo treatment. The results were inconclusive. Only after testing its antisense drugs in combination with other accepted treatments did the results begin to look better.
A similar pattern occurred many years ago in regard to various types of interferon being developed by Biogen and Schering Plough. Interferon initially was thought to be a miracle drug, which would cure everything from AIDS to cancer, to hepatitis, etc. Only after stratifying the patient population were they able to get positive results on SOME patients, complicated by some very undesirable side effects.
I'm less worried about the research results on Genasense than I am on the ability of the company to remain financially solvent. It doesn't do shareholders any good if the company comes up with an approved drug but in the meantime goes in hock to a wealthier drug company, eliminating most of the potential profits for existing shareholders. This is not just an idle worry. When Genentech was unable to find a large market for its landmark TPA drug for treating heart attacks, the company eventually entered into an agreement with Roche, which delivered most of the profits to Roche and not to Genentech shareholders.
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