Henry: Here is the story in today's Boston Globe about raloxifene. Hopefully the p.r. machine will take advantage of the widespread current interest to promote related developments at LGND.
Harrison Hickman
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Postmenopausal drug called promising
By Judy Foreman, Globe Staff, 06/08/97
One of the biggest decisions postmenopausal women face - whether to take supplemental estrogen, which protects the bones and heart but which may increase the risk of breast cancer - may become easier with a drug called raloxifene, now in the final stages of testing.
Many researchers are scrambling to find ways to help women get the
life-prolonging benefits of estrogen without incurring the risks that now cause many women to fear hormone supplements.
At a meeting last week in Washington sponsored by the National
Osteoporosis Foundation, researchers from Eli Lilly and Co. reported
preliminary findings on raloxifene from studies of the drug in 12,000 women in 25 countries.
The drug increased bone mineral density, a gauge of the risk of fracture, by 2 to 3 percent compared to a placebo, or dummy drug, the researchers said. It also lowered blood cholesterol.
Raloxifene, which would probably be marketed under the name Evista, also did not stimulate uterine tissue to grow or cause uterine bleeding. By contrast, estrogen can cause uterine bleeding and raise the risk of uterine cancer. To protect against the latter, many women who take estrogen also take another hormone, progesterone.
The study has been going on for two years and will continue for three more, the company said yesterday, although Lilly is expected to seek US Food and Drug Administration approval for raloxifene in mid-1997.
Although preliminary data suggest raloxifene protects against osteoporosis and heart disease without raising the risk of breast or uterine cancer, the long-term benefits and risks are unclear because the drug has only been in trials for a few years.
And one disadvantage of the new drug is that it increases hot flashes, while standard estrogen replacement therapy with drugs like Premarin prevents them.
Raloxifene is a member of a class of drugs called SERMS, or selective
estrogen receptor modulators. The first drug in this class, tamoxifen, has been used to treat women with breast cancer.
Tamoxifen acts both as an estrogen, which can stimulate cell growth, and an estrogen blocker. It acts as an estrogen in protecting bones and the heart, but blocks estrogen's action in the breast. Raloxifene works in similar ways and was considered as a treatment for breast cancer in the 1980s, but tamoxifen came along first.
Estrogen, tamoxifen, and raloxifene all work by binding to estrogen
receptors in various tissues throughout the body. While they all act the same way in bone, they act differently in other tissues, in part because different tissues have different types of estrogen receptors.
For instance, in bone cells, all three compounds protect against bone loss, said Donald McDonnell, a Duke University pharmacologist who studies hormones.
But in the breast, while estrogen induces cell growth, and therefore possibly cancer, tamoxifen and raloxifene block the growth-stimulating effects of estrogen.
The three estrogen-type drugs also have different effects in different tissues, because they cause estrogen receptors to twist into different physical shapes, or conformations. Estrogen typically causes the receptor to twist into one shape, while the other two compounds cause it to twist into another. These differently shaped molecules then trigger different effects on the cell's DNA, or genetic material.
While raloxifene and tamoxifen are similar, McDonnell said, raloxifene may have an advantage in terms of effects on the uterus. While tamoxifen can cause uterine cells to grow, raloxifene does not, he says.
The findings on raloxifene constitute ``a neat concept,'' says endocrinologist Dr. Michael Holick, director of the bone health care clinic at the Boston Medical Center.
``Raloxifene is a promising additional therapy to prevent bone loss in
perimenopausal and postmenopausal women who cannot take estrogen,''
Holick said. ``My preference would still be to use estrogen because we
don't know if raloxifene has the benefits on the entire cardiovascular system'' estrogen has.
While estrogen increases blood levels of ``good cholesterol'' and lowers ``bad cholesterol,'' raloxifene, according to Lilly, has been shown only to reduce bad cholesterol and total cholesterol and to have no effect on good cholesterol or triglycerides.
This story ran on page A07 of the Boston Globe on 06/08/97.
c Copyright 1997 Globe Newspaper Company. |
