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Biotech / Medical : Ligand (LGND) Breakout! -- Ignore unavailable to you. Want to Upgrade?

To: Bryce Elkins who wrote (18745)	4/6/1998 11:39:00 PM
From: Henry Niman	Respond to of 32384

Ble, If you heard C-SPAN today, you'll probably double up again tomorrow! I didn't catch all of it, but the take home message was loud and clear. Today's result was just a first step and the NCI will be moving forward very aggressively. Richard Klausner did most of the talking, with a few contributions from Leslie Ford and Norman Walmark. The NCI currently has 85 chemoprevention trials in progress. They are now getting ready to start a trial comparing Tamoxifen to Raloxifene (Evista), which should be music to the ears of LGND lovers. In fact they want to begin this trial immediately by enrolling the post menopausal women who were on the placebo. They will be offered entry into the new trial where they will be randomly assigned to receive Tamoxifen or Raloxifene. I suspect that the new trial is being underwritten by the NCI, with ZEN providing Tamoxifen and LLY providing Raloxifene. It's not that hard to envision subsequent trials pitting Targretin against the winner of the upcoming trial. Klausner certainly emphasized that today's results was a first step. he expect considerable advances over the "next 5-10 years". He specifically mentioned SERMs "at various stages of development". He also indicated that at the 20 mg/day for Tamoxifen, current treatment costs would be $80-$100 per month. The C-SPAN report was very detailed and LGND lovers should be very encouraged.

To: Bryce Elkins who wrote (18745)	4/7/1998 4:51:00 AM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

Here's the NY Times report. It contains much of the info seen on C-SPAN: By LAWRENCE K. ALTMAN ASHINGTON -- For the first time, a drug has been shown to prevent breast cancer among women at high risk for the disease, a jubilant group of federal health officials said Monday. Women who took the drug, tamoxifen, had 45 percent fewer cases of breast cancer than a group of women who took a dummy pill, or placebo. The drug helped all age groups in a large study, they said. The health officials called the study results historic and said they hoped they would lead to development of drugs to prevent other cancers. But because tamoxifen also carries risks of life-threatening adverse effects, such as cancer of the uterus, and blood clots that migrate to the lungs from veins in the legs, women were cautioned not to rush to demand the drug until statisticians and other experts do further analyses so that doctors can interpret the findings for individual women. Such analyses should take about two months, Dr. Harold Varmus, the head of the National Institutes of Health, said in an interview. The study was controversial from its beginning because many critics said the drug would have dangerous side effects. But federal officials stopped the study about a year before its scheduled completion, because an independent monitoring committee found that the drug's benefits clearly exceeded those that the experts had predicted in designing it. Women under age 50 in the study appeared to suffer no excess risk of adverse effects from tamoxifen, and overall, the tamoxifen users had fewer fractures of the hip, wrist and spine than the women who received the dummy pill. But on Monday, some critics of the drug said that it was premature to celebrate, because crucial questions still needed to be answered. Among these, the National Women's Health Network said in a news release, are: What, if any, additional risks will be found as the participants are followed for a longer time? Will there be fewer deaths in the long run? And what are the implications for women not at high risk for breast cancer? "As with any medication, the decision to begin tamoxifen therapy is a very complex one," Dr. Leslie Ford, an official of the National Cancer Institute, said. Ford also said that "even if a woman is at increased risk of breast cancer, tamoxifen therapy may not be appropriate for her" and "there are no simple answers." Because the study was not designed to determine the effects of tamoxifen among women who also took estrogen as a hormone replacement, the officials said they could offer no recommendations of the relative benefits and hazards of such therapies. Also, because the study began before the discovery that alterations in two genes, BRCA1 and 2, may predispose to breast cancer, the trial could not determine whether tamoxifen had unusual benefit for women carrying the genes. Tests are now planned to address the question over the next year, said Dr. Richard Klausner, the head of the cancer institute. The National Institutes of Health and the National Cancer Institute have spent $50 million to conduct the study since April 1992 among women 35 and older. Officials emphasized that the types of adverse effects that occurred in the study were anticipated before it began and that the incidence did not exceed expectations. However, an unexpected finding was that tamoxifen did not reduce the number of heart attacks. Tamoxifen has long been prescribed for women who have been treated for breast cancer, to prevent or delay recurrence of the disease. In the study, tamoxifen's benefits began almost immediately and continued for the four years of the study. But further research will be needed to determine how long a woman should take tamoxifen and whether safer and even more effective drugs can be found to prevent breast cancer, the officials said. Among those that might be tested are newer drugs known as selective estrogen-receptor modifiers, Klausner said. The prevention study was one of scores of trials conducted over recent decades at hundreds of hospitals in the United States and Canada by researchers based at the University of Pittsburgh. An earlier study provided hints that tamoxifen could prevent as well as treat cancer. Those who conducted the study are in the process of notifying all participants and had planned to hold a news conference later this week. But some participants notified reporters and the Philadelphia Inquirer first reported the news on Sunday. Doctors have used tamoxifen to treat breast cancer for 25 years and are free to prescribe it for prevention even without approval from the Food and Drug Administration. But the drug agency issued a news release saying it could not approve tamoxifen for prevention of breast cancer until it had thoroughly reviewed the information from the study. The FDA pledged to finish such a review within six months of receipt of the information. Zeneca Pharmaceuticals of Wilmington, Delaware manufactures tamoxifen, which is one of the most widely prescribed anti-cancer drugs in the world. Women who took tamoxifen in the study took two pills for a total of 20 milligrams a day. A month's supply costs from $80 to $100 in the United States. Because the risk of breast cancer increases with age, women aged 60 or older qualified to participate in the study on the basis of age alone. At age 60, about 17 of every 1,000 women are expected to develop breast cancer within five years. Women aged 35 to 60 were included if they were judged at high risk based on computer calculations of such factors as the number of first-degree relatives who had breast cancer; the number of breast biopsies undergone; age at which a first giving birth; age at which periods began; and whether the woman had a type of noninvasive breast cancer known as lobular carcinoma in situ. In the trial, invasive breast cancers developed in 85 of the healthy women who took tamoxifen, compared with 154 cases among the women who took the placebo. Eight participants died from breast cancer. Of these, three were among tamoxifen users and five were in the placebo group. The findings suggested that women 50 and older had a greater benefit from tamoxifen than younger women did, but this group was at increased risk for the serious adverse effects such as uterine cancer and blood clots. The adverse effects that were greater among the tamoxifen users than the placebo group included uterine cancer (33 cases vs. 14); pulmonary embolism, or blood clots in the lung (17 cases vs. six); and blood clots in major veins (30 cases vs. 19). The proportion of women in the United States who would have qualified for the study were as follows: at age 35, three in 1,000; at age 40, 27 in 1,000; at age 50, 93 in 1,000; and at age 55, 125 in 1,000. Although the cancer institute said extensive efforts had been made to enroll minorities in the study, blacks, Asians, Hispanics and other minority groups comprised only 3 percent of the total. In 1998, health officials anticipate that breast cancer will be diagnosed in more than 178,000 women in the United States, and that 43,500 women will die of the disease. In summarizing the study, Klausner said it "tells us that it is possible to prevent breast cancer and that tamoxifen is far from ideal." The study, he added, "is not an end, but rather a very propitious beginning" in finding improved prevention for breast cancer and other types of cancer.

To: Bryce Elkins who wrote (18745)	4/7/1998 4:58:00 AM
From: Henry Niman	Respond to of 32384

This is what was in the WSJ Interactive Edition: The Wall Street Journal Interactive Edition -- April 7, 1998 Drug Found to Prevent Breast Cancer Holds Serious Side Effects, Study Says Associated Press WASHINGTON -- A drug found to prevent breast cancer in half of high-risk women also causes serious side effects, researchers cautioned Monday, leaving women with a complex decision about the best course to protect their health. Federal officials said the breast cancer benefits from the drug are so clear that they cut short a long-term clinical trial and notified the 13,388 women participants of the findings. The 6,707 women in the study who had been taking a placebo, or dummy drug, will be told they could now start taking tamoxifen, officials said. As a side benefit, the study also showed that tamoxifen lowered the risk in older women of fractures of the back, neck or wrist due to brittle bones, or osteoporosis. In the study, the group of women taking the drug experienced 45% fewer cases of invasive breast cancer compared to those taking placebo. There were 85 invasive breast cancers among the tamoxifen group, vs. 154 in the placebo group. Women on tamoxifen also had fewer noninvasive breast cancers: 31 cases vs. 59 cases. Invasive cancer is that which spreads to adjacent tissue or organs, while noninvasive cancer is confined. There were 47 bone fractures among those on the drug, compared with 71 among those on placebo. But the side effects of the drug were significant and serious. Among the group on the drug, there were 33 cases of cancer of the uterine lining, vs. 14 cases in the placebo group. The drug group had 17 cases of blood clots in the lung, including two deaths. This compares with six cases and no deaths among the placebo group. "The results tell us that breast cancer can be prevented, but there is no simple take-home message," Dr. Richard Klausner, head of the National Cancer Institute, said at a news conference Monday. "There are important and serious side effects from this drug." Because the issue is so complex, Mr. Klausner said the cancer institute is developing guidelines to help women and their doctors decide when to use the drug, tamoxifen. In the drug group, there were 30 cases of blood clots in major veins, compared with 19 cases in the placebo group. In some women, tamoxifen also causes hot flashes and vaginal discharge, officials said. Tamoxifen should be used only by women at high risk, Mr. Klausner said. It doubles the risk of getting endometrial cancer, although that risk is about equal to that of women on estrogen replacement therapy. Tamoxifen also causes a tripling of risk for a blood clot in the lungs, a potentially fatal disorder. Nevertheless, tests of the drug, first reported over the weekend, mark "the first time in history that we have evidence that breast cancer can not only be treated, but also prevented," said Dr. Bernard Fisher, an Allegheny University professor and scientific director of the study that involved more than 13,000 women. Tamoxifen has been used for 25 years to treat breast cancer, but the study is the first to show the drug can prevent the disease in some women. The drug is known as an "anti-estrogen" because it blocks the effects of the hormone in some tissues and retards growth of cancer cells that depend upon estrogen. Mr. Klausner said it also is unclear just how long women should take the drug. The study lasted only six years, and some women took the drug for less, he said. Final effects of tamoxifen may still be years away, he said. "This is the first imperfect, but very encouraging step," he said, toward drugs that could protect people from lung, rectal, bowel or prostate cancer. About 85 other drugs are being tested for this preventive effect. Tamoxifen, made by Wilmington, Del.-based Zeneca Pharmaceuticals, is widely used to prevent the spread or return of breast cancer. U.S. shares of Zeneca Group, the British parent of Zeneca Pharmaceuticals, rose 7.1% Monday to close at $147 a share on the New York Stock Exchange, a gain of $9.75.

To: Bryce Elkins who wrote (18745)	4/7/1998 5:11:00 AM
From: Henry Niman	Respond to of 32384

Here's what Gruntal has to say about BRL's tamoxifen: Tamoxifen is the generic version of Nolvadex, the most popular anti- estrogen drug in the U.S. used to treat breast cancer as well as delay the recurrence of breast cancer after surgery. In 1993, Barr settled its patent challenge with the innovator Zeneca. Through this settlement, Barr received a $21 million one-time cash payment and entered into an agreement which allows Barr to purchase Tamoxifen directly from Zeneca and sell it as a generic product. Barr is the only distributor of Tamoxifen in the U.S. other than Zeneca, and has currently captured a 76% share of the Tamoxifen market. The company also has tentative FDA approval of their ANDA for Tamoxifen. This means that Barr will be able to manufacture the drug at the time of patent expiration in August of 2002, or before if some other company's patent challenge is successful. Taxomifen payments have provided Barr approximately $110 million of Tamoxifen (Nolvadex)pretax income since this settlement was initiated in 1993. In FY98, we are estimating $225 million in revenues stemming from the distribution of Tamoxifen, and thereafter revenues will possibly trend downward to reflect competition from other anti-estrogen agents such as Schering- Plough's Fareston, and Lilly's Evista.

To: Bryce Elkins who wrote (18745)	4/7/1998 5:25:00 AM
From: Henry Niman	Respond to of 32384

Here's some info on Fareston: Toremifene for Metastatic Breast Cancer in Postmenopausal Women From issue No. 240 (September, 1997) of Medical Sciences Bulletin More Medical Sciences Bulletin Articles Generic Name: Toremifene Citrate Trade Name: Fareston (Orion Corporation) Use: Treatment of metastatic breast cancer in postmenopausal women with estrogen receptor--positive or receptor-unknown tumors The breast is the most common cancer site in women, and breast cancer is second only to lung cancer as a cause of death in women. It is estimated that 1 of every 9 women will have breast cancer at some time in their lives. Between 1980 and 1987, the incidence of breast cancer increased by 32.5%. Approximately 60% to 70% of afflicted postmenopausal women have hormonally responsive disease. Because of its frequent and effective use in patients with breast cancer, tamoxifen is considered the agent of choice in the treatment of such patients. However, because the occurrence of endometrial cancer and the development of liver tumors in rats may be associated with tamoxifen, there has been renewed interest in the search for another agent that may be a better alternative for use in the treatment of breast cancer. Currently, toremifene and droloxifene are being studied in postmenopausal women for the treatment of advanced cancer. Thus far, the response rates have been shown to be similar to those for tamoxifen. Idoxifene, a tamoxifen analog, is also being studied. This drug was designed to have low carcinogenic potential. Another drug, raloxifene, is being studied for use in the prevention of postmenopausal osteoporosis; it may also reduce the risk of breast cancer. in these women as a beneficial side effect. How It Works Toremifene is a triphenylethylene derivative. It was developed to increase the therapeutic-to-toxic ratio of antiestrogens. Like tamoxifen, toremifene has both antiestrogenic and estrogenic properties. Also, as is true for tamoxifen, toremifene binds with a high affinity to cytoplasmic estrogen receptors. The antitumor activity of toremifene occurs independently of receptor binding. Clinical Tips When compared with the results of tamoxifen therapy, response rates to toremifene among postmenopausal breast cancer patients were not statistically different. In one study, it was noted that response rates, time to progression, and overall survival were superior for estrogen receptor-positive patients to these parameters as assessed in patients with estrogen receptor-negative disease. This same study concluded that toremifene is as safe and effective as tamoxifen for the treatment of postmenopausal, hormone receptor-- positive patients with metastatic breast cancer. Also, these researchers found that there was no beneficial effect with the use of a 200-mg/day rather than a 60-mg/day dose. Another study evaluated the use of toremifene for the treatment of patients who had previously failed to benefit from tamoxifen therapy. It was found that there were some patients in whom certain sites responded favorably while disease progression occurred at other sites. The authors thus concluded that high-dose toremifene therapy may be of some benefit in certain patients who have previously failed tamoxifen treatment. Yet another study found that response rate, response duration, survival, and toxicity were not significantly different between patients treated with tamoxifen and those taking toremifene. The authors concluded that these two antiestrogens are clinically cross-resistant in patients with advanced breast cancer. Although toremifene does not seem to perform better than tamoxifen in the treatment of breast cancer, it has been shown to be equally effective. Because there are concerns among members of the health-care community about the toxicity of tamoxifen, toremifene may serve as an excellent alternative to tamoxifen for the treatment of advanced breast cancer in postmenopausal women. References 1.Hayes DF, Van Zyl JA, Hacking A, et al. Randomized comparison of tamoxifen and two separate doses of toremifene in postmenopausal patients with metastatic breast cancer. J Clin Oncol.1995;13:2556-2566. 2.Jordan VC. Alternate antiestrogens and approaches to the prevention of breast cancer. J Cell Biochem. 1995;22:51-57. 3.Pyrohen S, Valavaara R, Vuorinen J, Hajba A. High dose toremifene in advanced breast cancer resistant to or relapsed during tamoxifen treatment. Breast Cancer Res Treat. 1994;29(3):223-228. 4.Stenbygaard LE, Herrstedt J, Thomsen JF, et al. Toremifene and tamoxifen in advanced breast cancer -- a double-blind cross-over trial. Breast Cancer Res Treat. 1993;25:57-63.

To: Bryce Elkins who wrote (18745)	4/7/1998 5:50:00 AM
From: Henry Niman	Respond to of 32384

More info on the BCPT can be found at: breastcancer.net

To: Bryce Elkins who wrote (18745)	4/7/1998 5:53:00 AM
From: Henry Niman	Read Replies (2) \| Respond to of 32384

Here's more detail on fareston: Fareston Now Available As First-Line Treatment Of Metastatic Breast Cancer MADISON, NJ -- December 3, 1997 -- Schering-Plough Corp. today announced Fareston(R) (toremifene citrate) 60 mg Tablets is now available nationwide as a first-line treatment for metastatic breast cancer in postmenopausal women with estrogen receptor positive or unknown tumours -- estimated to affect more than 135,000 American women in 1997. Fareston, the first new antiestrogen treatment for breast cancer to become available in the United States in 19 years, received marketing clearance from the U.S. Food and Drug Administration in May. The drug is a once-daily oral antiestrogen that reduces breast tumour size by binding to estrogen receptors on breast cancer cells, thereby blocking estrogen from further stimulating tumour growth. Schering-Plough has marketing rights to Fareston in the U.S. and Canada as well as in certain other countries through an exclusive agreement with Orion Corp. of Finland. Breast cancer is the most common form of cancer in women in the U.S. and is the leading cause of cancer death for U.S. women between the ages of 40 and 55. It is estimated that some 44,000 U.S. women will die from the disease in 1997, according to the National Cancer Institute. Fareston is indicated for first-line use in the treatment of metastatic breast cancer in postmenopausal women with estrogen receptor positive or unknown tumours. It is contraindicated in patients with known hypersensitivity to the drug. The chemical structure of Fareston differs from that of tamoxifen, a widely-used antiestrogen, by the substitution of a chlorine atom for a hydrogen atom in the 4-position of the ethyl prosthetic group of the molecule. The chlorine atom may prevent the generation of reactive metabolites that bind DNA and are characteristic of tamoxifen metabolism. (The clinical significance of these data has not been demonstrated.) A New Drug Application (NDA) for Fareston was filed in December 1994 by Orion Pharma. Support for the NDA included data from three clinical trials involving a total of 1,526 patients who had no prior therapy for advanced breast cancer and were estrogen receptor positive or receptor unknown. These trials demonstrated that Fareston is a safe and effective alternative to tamoxifen as a first-line treatment of metastatic breast cancer in postmenopausal patients. The most frequently reported side effects associated with the drug include hot flashes, sweating, nausea and vaginal discharge. These adverse reactions typically occur at the beginning of treatment. During the three trials, only about one percent of the patients receiving Fareston 60 mg discontinued treatment as a result of adverse effects. As with other antiestrogens, tumour flare, hypercalcemia and vaginal bleeding have been reported in some breast cancer patients. The drug is currently available in several countries for the treatment of advanced breast cancer. In February 1996, the European Union's (EU) Commission of the European Communities granted marketing authorization to Fareston as a first-line treatment of hormone-dependent metastatic breast cancer in postmenopausal women. The marketing authorization is valid in all 15 EU-member states. More information on: Fareston, Schering-Plough Corp.

To: Bryce Elkins who wrote (18745)	4/7/1998 6:01:00 AM
From: Henry Niman	Respond to of 32384

Here's a NEJM review on SERMs (TSEs): The New England Journal of Medicine -- December 4, 1997 -- Volume 337, Number 23 Tissue-Specific Estrogens -- The Promise for the Future As life expectancy continues to increase, women will soon be postmenopausal for one third of their lives. The human and economic costs of this increased longevity in an estrogen-deficient state are substantial. They include a projected increase in cardiovascular events, the leading cause of death among postmenopausal women, and in osteoporotic hip fractures, which are associated with a 20 percent mortality rate within the first year. However, despite the well-established efficacy of estrogens in protecting women against cardiovascular disease and maintaining bone density and reducing fractures, less than one fifth of postmenopausal women ever take them. (1) Furthermore, the proportion who take estrogen for a prolonged period -- an important prerequisite for efficacy -- is even smaller because of the reluctance of physicians to prescribe estrogens and of women to accept such a prescription. This reluctance is based on the high incidence of side effects: vaginal bleeding, breast swelling and tenderness, and an increased risk of endometrial and breast cancer. (1) Hence the pressing need for "designer estrogens," a growing family of compounds also known as selective estrogen-receptor modulators. These tissue-specific estrogens were designed to preserve the beneficial effects of estrogens, including protection against cardiovascular diseases and osteoporosis, but to have no undesired effects on the reproductive organs. Raloxifene is one of these compounds. In ovariectomized rats it maintains bone mineral density and improves the serum lipid profile but has little estrogenic action on breast or uterine tissue. (2) In humans, too, it has a favorable effect on bone remodeling and serum lipid concentrations. In this issue of the Journal, Delmas et al. report a two-year randomized, placebo-controlled, dose-ranging trial of raloxifene in 601 normal white postmenopausal women. (3) At a dose of 60 mg per day, raloxifene maintained bone mineral density, lowered serum concentrations of total and low-density lipoprotein (LDL) cholesterol, and did not stimulate the endometrium. Specifically, the bone mineral density of the lumbar spine, total hip, femoral neck, and total body increased slightly (1.2 to 1.6 percent) in response to treatment with raloxifene. Serum concentrations of total cholesterol decreased by 6.4 percent and those of LDL cholesterol decreased by 10 percent after three months, with no significant change thereafter. Serum concentrations of triglycerides and high-density lipoprotein (HDL) cholesterol did not change. These beneficial effects on the skeleton and serum lipid profile are similar to those of tamoxifen (4,5) -- which, however, causes endometrial stimulation -- but are less strong than those of estrogen. Unlike estrogen, none of the selective estrogen-receptor modulators, including raloxifene, increase the serum concentrations of HDL cholesterol, an independent marker of protection against cardiovascular disease. The protective cardiovascular effect of estrogen is also partially mediated by an estrogen-induced vasodilatory effect and an antioxidant effect on lipoproteins that decreases their atherogenic potential. Similarly, raloxifene also inhibits LDL oxidation (6); however, its effect on vascular tone is undetermined. The beneficial skeletal effect of raloxifene seems to be due mostly to an antiresorptive action on bone, thus inducing a positive calcium balance when administered over a long period at a dose of 60 mg per day. (7) Like estrogen, tamoxifen decreases plasma antithrombin III and fibrinogen concentrations; the effect of raloxifene on these substances and on the incidence of thrombophlebitis is not known. The key role of estrogen and its receptor in the normal physiology of the skeleton and the reproductive organs is illustrated in two human syndromes, aromatase deficiency and estrogen-receptor-gene defect. Both are characterized by severe estrogen deficiency, the former because little estrogen is produced and the latter because of resistance to its action. Affected patients have incomplete epiphyseal fusion, with continued linear growth into adulthood, osteoporosis, and lack of sexual development in addition to insulin resistance. (8,9) The central role of the estrogen receptor in skeletal physiology is further illustrated by studies aimed at elucidating the mechanism (or mechanisms) of action of estrogens and antiestrogens. Estrogens bind to the estrogen receptor, inducing a conformational change that leads to activation of gene transcription through specific estrogen-response elements of target genes. Transcriptional activation of these genes is thought to occur through two distinct domains of the estrogen receptor, AF-1 and AF-2. Differential activation of these two domains by estrogens and antiestrogens explains the tissue selectivity of the latter. Peptide growth factors stimulate estrogen-dependent transcriptional activation of estrogen-response elements and are themselves activated by the estrogen receptor. Indeed, estrogens and raloxifene may partially maintain bone mass through regulation of the gene for transforming growth factor (beta) (TGF-(beta)) by means of the estrogen receptor. Deletion of the ligand-binding domain of the estrogen receptor abolishes both estradiol- and raloxifene-induced activation of the TGF-(beta) promoter. However, deletion of the AF-1 domain of the estrogen receptor abolishes estradiol- but not raloxifene-induced TGF-(beta) activation, and deletion of the AF-2 domain abolishes raloxifene- but not estradiol-induced activation of the TGF-(beta) promoter. (10) The promising results of the study by Delmas et al. pave the way for important additional investigations. Despite the beneficial effects of raloxifene on bone mineral density and the serum lipid profile, its effect in preventing fractures and cardiovascular events is yet to be determined. The absence of vaginal bleeding and of endometrial or breast stimulation reported by Delmas et al. in women receiving raloxifene, as well as preliminary results demonstrating a decrease in the risk of breast cancer (reported at the National Osteoporosis Foundation Meeting in Washington, D.C., in June 1997), are added benefits that should improve compliance among women taking this new type of hormone-replacement therapy. However, 25 percent of the women in the trial reported by Delmas et al. discontinued therapy. The proportions were similar in all treatment groups, as were the proportions experiencing hot flashes. The absence of an increase in hot flashes among the women given raloxifene is surprising; an increase, such as occurs with tamoxifen, might have been expected. The favorable effect of raloxifene on bone mineral density and serum lipid concentrations and the absence of any effect on endometrial histology are quite encouraging. The decrease in estrogen-related adverse effects with the selective estrogen-receptor modulators in general and raloxifene in particular should improve compliance and decrease the incidence of cardiovascular events and fractures while not increasing breast cancer. The challenge is to realize this promise. Ghada El-Hajj Fuleihan, M.D., M.P.H. American University of Beirut Beirut, Lebanon

To: Bryce Elkins who wrote (18745)	4/7/1998 6:20:00 AM
From: Henry Niman	Read Replies (3) \| Respond to of 32384

Here's LGND's latest patent: United States Patent 5,733,738 Niman Mar. 31, 1998 Polypeptide-induced monoclonal receptors to protein ligands Inventors: Niman; Henry L. (Carlsbad, CA). Assignee: Ligand Pharmaceuticals (San Diego, CA). Appl. No.: 418,898 Filed: Apr. 7, 1995 Related U.S. Application Data Continuation of (including streamline cont.) Ser. No. 925,815, Aug. 4, 1992, abandoned, which is a continuation of Ser. No. 779,143, Oct. 21, 1991, abandoned, which is a continuation of Ser. No. 393,267, Aug. 12, 1989, abandoned, which is a continuation-in-part of Ser. No. 232,395, Aug. 12, 1988, abandoned, which is a continuation-in-part of Ser. No. 118,823, Nov. 9, 1987, abandoned, which is a continuation-in-part of Ser. No. 39,534, Apr. 16, 1987, Pat. No. 5,015,571, which is a continuation-in-part of Ser. No. 736,545, May 21, 1985, abandoned, which is a continuation-in-part of Ser. No. 701,954, Feb. 15, 1985, Pat. No. 5,030,565, which is a continuation-in-part of Ser. No. 524,804, Aug. 17, 1983, abandoned. Intl. Cl. : G01N 33/574 Current U.S. Cl.: 435/7.23; 436/503; 436/548; 436/813 Field of Search: 424/138.1, 155.1, 174.1; 435/7.23, 240.27; 436/503, 548, 64, 813; 530/324, 325, 326, 327, 328, 329, 387.7, 388.8, 389.7, 808, 828 References Cited \| [Referenced By] U.S. Patent Documents 4,452,901 Jun., 1984 Gordon et al. 435/7 4,532,220 Jul., 1985 Lavi 436/813 X 4,535,058 Aug., 1985 Weinberg 436/813 X 4,786,718 Nov., 1988 Weinberg et al. 436/813 X 5,030,563 Jul., 1991 Niman et al. 435/70.21 5,081,230 Jan., 1992 Carney 530/387 Foreign Patent Documents 0108564 Oct., 1983 EP 0177814 Sept., 1985 EP 0203587 May, 1986 EP 0318179 Nov., 1988 EP 8403087 Feb., 1984 WO Other References "Oncogenes and oncagene proteins", Brandt-Ravt et al. Occupational Medicine: State of the Art Reviews 2(1) pp. 27-38 (1987). "Activation of H ras Oncogene in Rat Bladder Tumors induced by N-Betyl-N-(4 Hydroxybutyl) Nitrosamine" Fujita et al., J. Natl. Cancer Inst. 80(1): 37-43, 1988. Brandt-Rauf, et al, "Serum Oncogene Proteins in Foundry Workers," J. Soc. Occup. Med. (1980), vol. 40, pp. 11-14. Brandt-Rauf, et al, "Serum Oncoproteins and Growth Factors in Asbestosis and Silicosis Patients," Int. J. Cancer, (1992) vol. 50, pp. 881-885. Forth et al. Monoclonal Antibodies to the p 21 Products of the Transforming Gene of Harvey Murine Sarcoma Virus and of the Cellular rasGene Family. J. Vrol. 43:294-304. Brandt-Rauf, P., Occupational Medicine: State of the Reviews 5:59-65 (1990). Brandt-Rauf, P. and Niman, H.L., British J. Indus. Med. 45(10): 689-693 (Oct. 1988). Brandt-Rauf, P., J. Occup. Med. 30: 399-404 (May 1988). Brandt-Rauf, P., et al., J. Soc. Occup. Med. 39: 141-143 (1989). Green, et al., Cell 28: 477-487 (Mar. 1982). Sutcliffe, et al., Science 219: 660-666 (Feb. 1983). Wilson, et al., Cell 37: 767-778 (1984). Bizub, et al.Oncogene 1: 131-142 (1987. Niman, et al.PNAS-USA 82: 7924-7928 (Dec. 1985). Primary Examiner: Saunders; David Attorney, Agent or Firm: Lyon & Lyon LLP Abstract The present invention relates to immunological receptors and ligands, and more particularly to monoclonal receptors raised to peptides whose amino acid residue sequences correspond to sequences of retroviral ligands. The receptors are used to assay body samples from a host to indicate exposure of the host to a carcinogen. 6 Claims, 58 Drawing Figures

To: Bryce Elkins who wrote (18745)	4/7/1998 8:09:00 AM
From: tonyt	Read Replies (2) \| Respond to of 32384

Too bad that none of the 20+ press releases posted had any mention of LGND.

To: Bryce Elkins who wrote (18745)	4/7/1998 8:27:00 AM
From: Henry Niman	Respond to of 32384

Evista (Raloxifene) is slated for the new prevention trial, but neither LLY nor Evista was mentioned in the recent popular press coverage. Even though Raloxifene was mentioned, most viewers would not know that Raloxifene is Evista. I think that some posters have unrealistic expectations of the popular press. When the NY Times: www3.techstocks.com, Business Week On-Line: Message 3462385 and Financial Times did reviews on new treatments fo diabetes, LGND was mentioned. When the WSJ did a review of designer estrogens: home.att.net LGND was mentioned. Future reviews on breast cancer prevention drugs will mention LGND. Recent news is breaking news which generally do not include reviews.