JO, Using Evista to treat breast cancer should not come as a surprise. In fact that is precisely what the LGND/LLY research program targets (although the actual compounds may be second generation SERMs and second generation Rexinoids). I did see C-SPAN coverage yesterday as well as CNN. I expect coverage to continue to be intense, especially since there will be several reports at ASCO next month on Evista and breast cancer prevention.
Thus, it's probably time to do another conceptual review. ZEN's Tamoxifen has been approved for treating breast cancer and AHP's Premarin has been approved hormone replacement treatment (HRT). Both drugs target the estrogen receptor. Premarin has been shown to offer several benefits including strengthening bones and protecting the heart. It has also been shown to increase the risk for breast cancer as well as uterine cancer.
Tamoxifen has been called an anti-estrogen because it can block estrogen from binding to its receptor. It was approved for treating breast cancer, but the recent trial tested its ability for preventing breast cancer. It was shown to be effective (reduces incidence by 45% in high risk patients), but had significant side effects (uterine cancer and blood clots), which affect a significant number of patients.
Evista is another SERM. It has been approved for the prevention of osteoporosis and the upcoming presentation will show that in some cases, it too can prevent breast cancer (at rates of 58% and 74%), It may not have as big of a risk at causing uterine cancer, but it also causes blood clots.
Several companies are working on additional SERMs. PFE's most advanced compound is Droloxifene. It was initially in trials for treating breast cancer. Its efficacy was about the same as Tamoxifen, so PFE just switched it to a trial for the prevention of breast cancer. It is also in trails for prevention of osteoporosis as is another PFE compound identified by LGND (CP-366,156) and an AHP compound, TSE424, also identified by LGND.
Thus there are several SERMs in the clinic (SBH has Idioxifene), most of which are being tested for prevention of osteoporosis, but also could have breast cancer prevention and treatment properties.
In animals Targretin is similar to Tamoxifen for breast cancer prevention and superior for breast cancer treatment. Moreover, it synergizes with Tamoxifen for both applications. Thus Targretin could be used as monotherapy as well as combination therapy. It is currently in clinical trials for both applications for treating breast cancer (in Phase II trials in combination with Tamoxifen and in Phase II/III trials for monotherapy). It is likely that it will also synergize with the other SERMs in the clinic.
I'm not sure what SERM-3 is, but suspect that it is a third generation SERM of LLY (with Evista being considered a second generation SERM and Tamoxifen being a first generation SERM). |
