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

To: Alper H.YUKSEL who wrote (21010)	5/18/1998 4:34:00 AM
From: Henry Niman	Respond to of 32384

Alper, The Herceptin article is linked to the front page of WSJ Ineractive at wsj.com . Looks like (breast) cancer is beginning to get the attention that it deserves. The Herceptin article is also linked to LGND: Enter Symbol: Health: A New Study Flags Advances In Cancer Drugs The Wall Street Journal--May 18, 1998 Ligand Pharma 1Q Losses 35c/Diluted Shr Vs 32c Dow Jones Newswires--May 15, 1998 Health Brief -- LIGAND PHARMACEUTICALS INC.: Purchase Pacts Are... The Wall Street Journal--May 12, 1998 Ligand Pharma To Buy Seragen For $67M In Cash, Stock Dow Jones Newswires--May 11, 1998 Ligand, SmithKline Get OK To Add Leptin-Obesity Research Dow Jones Newswires--April 27, 1998 Ligand: Panretin Capsules Effective Against Kaposi's Sarcoma Dow Jones Newswires--April 7, 1998 Company Symbols For Stories 7 p.m. - 12 a.m. Thur., Mar. 26 Dow Jones Newswires--March 27, 1998 Ligand Reports Positive Results For Phase III Panretin Trial Dow Jones Newswires--March 26, 1998 Ligand: Wyeth-Ayerst Submits INDA For Osteoporosis Compound Dow Jones Newswires--March 26, 1998 SmithKline, Ligand Pharma To Expand Collaboration Dow Jones Newswires--March 18, 1998 Eli Lilly Extends Ligand Pharma Specialty Product Option Dow Jones Newswires--March 9, 1998 R.P. Scherer, Ligand Pharma To Develop Oral Capsules Dow Jones Newswires--March 6, 1998 Ligand Pharma Expands Panretin Gel Phase I/II Data Dow Jones Newswires--March 1, 1998 Cytel Corp Gets Rts To Ligand Pharma Unit Patents>CYTL LGND Dow Jones Newswires--February 24, 1998 Who's News: Ligand Pharmaceuticals Inc. The Wall Street Journal--February 24, 1998

To: Alper H.YUKSEL who wrote (21010)	5/18/1998 5:06:00 AM
From: Henry Niman	Respond to of 32384

Today's NY Times also has an article on Herceptin and breast cancer. No mention of LGND, but targeting a growth factor receptor that is over expressed on the surface of tumor cells is discussed and that's just what DAB389-IL2 (ONTAK) does against CTCL tumors over expressing IL-2 receptors and DAB389-EGF does against a variety of tumors (including breast cancer) over expressing EGF receptors: Drug Shown to Shrink Tumors in Type of Breast Cancer Related Articles Study Shows Tamoxifen Being Prescribed to Too Few Breast Cancer Victims (May 15) Study Shows a Drug Can Help Prevent Breast Cancer (April 7) Study: Exposure to DDT Doesn't Increase Risk of Breast Cancer (Oct. 30, 1997) The New York Times: Women's Health By LAWRENCE K. ALTMAN OS ANGELES -- The first full-scale trials of an experimental drug that attacks a genetic defect in breast cancer cells show significant promise for women with advanced cancer, scientists reported Sunday. The drug, Herceptin, heightened the benefits of chemotherapy by shrinking tumors and slowing progression of a particular type of breast cancer, one that is responsible for about 30 percent of the 180,000 new cases of the disease in the United States each year, the scientists said at the annual meeting of the American Society of Clinical Oncology here. The improvement was seen among cases that had failed standard therapies. Participants at the meeting greeted the reports with cautious optimism, and leaders said they were now planning to test the drug, which was developed by Genentech of South San Francisco, Calif., among patients with less advanced forms of the breast cancer and among the 20 percent of ovarian cancer cases involving the same genetic defect. The University of California at Los Angeles, where much of the initial research on this form of breast cancer was conducted, issued a news release calling the development of the experimental treatment "a significant medical breakthrough." Other experts agreed that it was a breakthrough. But they said their excitement primarily reflected a hope that with further research similar drugs could be developed for many types of tumors, opening a new frontier in cancer therapy. If such therapies do not prolong life, they may help people with advanced cancer work longer and enjoy life more. But the experts cautioned the public not to expect sudden success and stressed that it would take years, and millions of dollars, to complete such research. Genentech said that the Food and Drug Administration had granted Herceptin "fast track" status and that the agency would decide by Nov. 4 whether to approve it. Until then, the drug is available only to participants in clinical trials and through a lottery under which Genentech is providing enough Herceptin for 100 women each quarter. The number may expand to 200 each quarter this summer. Paul Laland, the chief spokesman for Genentech, said the company would be able to provide enough for about 50,000 women -- the anticipated need -- by the end of the year. Herceptin is a protein known as a monoclonal antibody that was genetically engineered to bind to other specific proteins. The preliminary success with Herceptin and another monoclonal antibody for lymphoma was expected to revive interest in developing such compounds, a research avenue that scientists abandoned a decade ago because of lack of success. Although Herceptin can cause heart damage when combined with certain other anti-cancer drugs, the scientists who conducted the studies said it was remarkably safe for an anti-cancer drug. The studies reported Sunday were conducted in a number of medical centers throughout the world and involved women with a particularly aggressive form of cancer known as HER-2/neu. The cancer can progress rapidly to cause death sooner than other breast cancers. At news conferences and presentations at the meeting here, attended by more than 19,000 cancer specialists, the scientists said they were impressed that weekly intravenous injections of Herceptin showed significant benefit among women who had cancers that had not responded well to standard treatment, including the most drastic -- bone marrow transplants. In one trial, women were treated with chemotherapy alone or Herceptin and chemotherapy. The addition of Herceptin led the cancers to completely disappear or shrink by half or more in 114 of 235 women, or 49 percent. This compared with 74 of 234, or 32 percent, in the group that received only chemotherapy. After one year, 78 percent of those receiving Herceptin and chemotherapy were alive compared with 67 percent who received chemotherapy alone. Because the full-scale studies began in 1995 and patients were still entering the studies last year, it was too soon to know how long the benefits would last, the scientists said. After one year, about 28 percent of women treated with Herceptin and chemotherapy did not show evidence of cancer progression compared with 14 percent of the women treated with only chemotherapy. The median duration of response -- from the time the cancer shrank to the time it began to enlarge or spread -- was nine months in the Herceptin group compared with six months in the chemotherapy group. The second trial tested Herceptin alone. In this study, the cancer either completely disappeared or shrank by more than half in 34 of 213 participants, or 16 percent. The median duration of response was slightly more than nine months. There were hints that the effects might be long lasting. Dr. Dennis Slamon of the University of California at Los Angeles and Dr. Larry Norton of Memorial Sloan-Kettering Cancer Center in New York City, principal investigators in the research, said they had treated two women in earlier phases of the studies who have survived for six and five years respectively. The woman who has survived for six years took Herceptin for only 18 weeks and none since, Slamon said. The woman who has survived five years is still taking Herceptin, Norton said. Statistically, the women would have been expected to die in less than a year without such treatment, the scientists said. Although the improvements from Herceptin therapy may seem small to nonphysicians, Norton said at a news conference that the drug had "a big effect, not a small, minor effect." Norton, who was a principal investigator of one study, also said that "this is the biggest difference I have ever seen in advanced breast cancer." The way Herceptin works -- by targeting a molecule -- "is not like anything we have ever seen before" in cancer therapy, Norton said. Because of its novelty, he said, doctors will have to learn the optimal way to use it in practice. With experience from additional clinical trials involving women with earlier stages of breast cancer, several experts said they expected that doctors would eventually widely prescribe Herceptin when the cancer was confined to the breast or lymph nodes in the armpit. The Herceptin studies involved women who have an overabundance of the gene HER-2/neu in their cancerous breast cells. The gene is not inherited and develops for unknown reasons during life. The gene was discovered in 1985, and since then studies have indicated that about 30 percent of women with breast cancer have HER-2/neu. Tests on the breast cancer itself can detect the gene, but they are not available at all hospitals and Slamon cautioned that there is wide variation in the quality of the testing that is performed. The genes produce a specific protein found on the surface of the cancerous breast cell, and that acts as a receptor for other molecules, called growth factors, that help regulate cell growth. Cancer is characterized by uncontrolled replication of cells. Breast cancer occurs when, for unknown reasons, women develop up to 20 extra copies of the gene. HER-2/neu is also found in about 20 percent of ovarian cancers, and the researchers will expand studies to include ovarian and other forms of cancer. The scientists said Herceptin lacked the usual serious side effects of standard chemotherapy such as hair loss and significant decreases in blood counts. Herceptin causes chills and mild fever in about a third of women when they first take the drug. But the symptoms are usually quickly relieved with acetaminophen and similar drugs. Experts said there was no way to know without further studies how long women would need to take Herceptin. Fran M. Visco, president of the National Breast Cancer Coalition, said her group had urged women to participate in the trials of Herceptin. Dr. Susan Hellmann, Genentech's chief medical officer, said the study leaders would not have been able to enroll as many women in the same period without the group's cooperation.

To: Alper H.YUKSEL who wrote (21010)	5/18/1998 5:13:00 AM
From: Henry Niman	Respond to of 32384

Of course on Friday, Jesse Eisinger began covering ASCO: archive.thestreet.com He mention GNE's Herceptin as well as LLY's Evista as hot topics and also mentioned how SEQU drug approved for Kaposi's Sarcoma was generating significant off-label cancer sales.

To: Alper H.YUKSEL who wrote (21010)	5/18/1998 5:18:00 AM
From: Henry Niman	Respond to of 32384

The Barron's article is generating quite a high hitting frequency at home.att.net (Biotech Boom table), especially for a weekend. Looks like things are beginning to heat up.

To: Alper H.YUKSEL who wrote (21010)	5/18/1998 6:02:00 AM
From: Henry Niman	Respond to of 32384

CNBC is discussing Herceptin this morning. Here's the AP version: New Cancer Treatment Shows Success By DANIEL Q. HANEY .c The Associated Press AP Medical Editor LOS ANGELES (AP) - Diagnosed with an especially aggressive case of breast cancer, Virginia Empey pleaded and prayed for a last chance - an experimental treatment aimed at taming the bad genes fueling her disease. Against the odds, she got into a study of the drug Herceptin and the tumors swelling her liver began to shrink. Three years later, she is a ''full-time grandmother'' who's thinking about dancing lessons. ''I feel like I have been blessed by being in the right place at the right time,'' said Empey, 53, a former school nurse administrator from Bakersfield, Calif. Attacking cancer at its genetic roots has been a goal of science for two decades. Researchers say they now have the first evidence that they can actually do it, pointing to success in an entirely new approach to fighting cancer. The maker of Herceptin, Genentech Inc., hopes that it will be approved and put on the market by next fall. It could quickly become a standard treatment for the one-quarter or more of breast cancer patients whose tumors are driven by multiple copies of a gene called HER-2 - and while it substantially boosts the power of ordinary chemotherapy, it carries none of the usual cancer drug side effects, such as nausea and hair loss. Perhaps even more important, doctors say, is that the treatment works at all - it shows that one of the hottest areas of cancer research is likely to pay off. ''This proves the paradigm. If we understand what is broken in the malignant cell, we may be able to fix it,'' said Dr. Dennis Slamon of the University of California, Los Angeles, whose basic research into cancer genes helped spur the drug's development. Dozens of other drugs in earlier stages of development are also aimed at sidestepping a variety of genetic flaws that make tumors grow uncontrollably; several could be available in the next few years. Results of the first large studies of Herceptin were presented Sunday at the society's annual scientific meeting, attended by about 18,000 cancer specialists. Doctors tested it on women with invariably fatal advanced breast cancer that had spread to other parts of their bodies. When added to standard treatment, they found it lengthened lives an average of three months. While this may seem modest, researchers said it represents a major impact in such a late stage of the disease. Researchers are unsure of the treatment's ultimate impact on survival, but a few cases suggest it could be substantial in those with the HER-2 defect. Typically, patients like Empey die within 10 to 18 months after the cancer spreads. However, one of the earliest patients to get Herceptin is still alive after almost six years and another has survived nearly four years. Researchers predict the results could be much more impressive when the drug is given before it has moved beyond the breast and lymph nodes. ''There is absolutely no question that there will be a lot of use of this drug once it's available,'' said Dr. Larry Norton of Memorial Sloan Kettering Cancer Center in New York, one of the doctors who tested it. Genentech financed two studies presented at the conference by Slamon and Dr. Melody Cobleigh of Rush-Presbyterian-St. Luke's Medical Center in Chicago. The path of scientific discovery began in the 1980s, when Dr. Robert Weinberg of Massachusetts Institute of Technology discovered HER-2. The gene produces a protein on the surface of cells that serves as a receiving point for growth-stimulating hormones. Twelve years ago, Slamon's team found that about 30 percent of women with breast cancer have many extra copies of this gene. The result: Their breast cells reproduce out of control and spread through their bodies. It is much more aggressive than breast cancer fueled by other genetic flaws. Scientists reasoned they might reduce HER-2's impact by somehow blocking the extra hormone docking points created by the gene. At Genentech, scientists cloned antibodies designed to do this. One turned out to be Herceptin, the first treatment designed from start to finish to attack a specific genetic error unique to cancer cells. Researchers tested it on 691 women with spreading breast cancer who carried extra copies of HER-2. Among those who had not been previously treated, doctors compared standard chemotherapy alone to chemo plus Herceptin. They found that tumors shrank at least 50 percent in half of the women getting Herceptin, compared with one-third taking chemo only. The cancers resumed growing an average of 7.6 months later in the Herceptin patients, but this was three months later than in the other women. The researchers also tested Herceptin alone in women who had relapsed after standard chemotherapy. In 4 percent the tumors disappeared completely, and they shrank by at least half in another 12 percent. The drug is given once a week in half-hour infusions. Doctors are still unsure whether the treatment can ever be safely stopped or whether patients need to take it for the rest of their lives. Slamon recommended that breast cancer patients ask their doctors to check them for HER-2, since this is not routinely done. Although the drug will not be routinely available until it wins Food and Drug Administration approval, small amounts are distributed through the National Cancer Institute. Those interested in entering the lottery for Herceptin can obtain information by calling the National Cancer Institute at 800-4-CANCER. AP-NY-05-18-98 0303EDT

To: Alper H.YUKSEL who wrote (21010)	5/18/1998 6:04:00 AM
From: Henry Niman	Respond to of 32384

Here's more on Herceptin: First Use of Monoclonal Antibody to Fight Metastatic Breast Cancer Slows Progression of Cancer and Increases Tumor Shrinkage, According to Researchers at Rush-Presbyterian-St. Luke's Hospital CHICAGO, May 17 /PRNewswire/ -- The use of a monoclonal antibody has slowed the progression of cancer and increased tumor shrinkage in women with metastatic breast cancer, according to Rush researchers who presented their finding at the annual meeting of the American Society of Clinical Oncology in Los Angeles on May 17. The monoclonal antibody, Herceptin, targets the HER2 gene, a growth factor receptor protein that is produced in excess, "overexpressed," in many women with metastatic breast cancer, according to Dr. Melody A. Cobleigh, an investigator of the study, which was conducted at Rush and a number of academic medical centers across the country over the past three years. Herceptin is produced by Genentech, Inc., in South San Francisco, Calif. "The results of these studies are impressive and encouraging since we will now have another treatment option, a new, nontoxic biologic approach, for women with this aggressive form of breast cancer," said Cobleigh. If Herceptin is approved by the Food and Drug Administration, it will be the first treatment that specifically targets this aggressive form of breast cancer that is associated with more rapid cancer progression and shortened survival. It is the first therapy that was developed to target a specific protein defect that contributes to the malignant progression of cancer. HER2 overexpression occurs in 25 to 30 percent of patients with breast cancer. The Herceptin monoclonal antibody works by binding to the HER2 growth factor receptors present in excessive amounts on the surface of the cancer cells, slowing the growth of HER2 human breast cancer cells. Two companion Phase III studies were done. In one, patients were treated with Herceptin alone. In the other, they were treated with Herceptin in combination with chemotherapy. Herceptin Alone Trial This part of the study (Rush was the only midwest participant) evaluated the overall response rate and safety when using Herceptin as a single agent without chemotherapy. The study included 222 women with metastatic breast cancer and excessive HER2 who had a recurrence of the disease following treatment. The cancer in these women failed to respond to two kinds of prior chemotherapy, and more than a quarter had received bone marrow transplants. Overall, 16 percent of the patients experienced slowed progression of the disease and tumor shrinkage. Eight patients experienced a complete remission of the disease (4 percent), and 26 (12 percent) experienced a partial remission. The median duration of response, measured from the time the cancer responds to treatment to the time when the cancer begins to enlarge or spread again, was nine months. "A 16 percent response rate and nine-month duration of response is particularly impressive given the seriousness and aggressive nature of metastatic breast cancer. Patients will have another option that is active as a single agent. Because toxicity is low, the women's quality of life while on therapy can be maintained," said Cobleigh. Herceptin Plus Chemotherapy Trial For this part of the study, patients were treated with Herceptin in combination with chemotherapy -- either paclitaxel or doxorubicin plus cyclophosphamide (DC). This trial included 469 women who had tumors that overexpressed HER2 who had not been previously treated with chemotherapy for their metastatic disease. In more than 25 percent of women treated with Herceptin plus chemotherapy, progression of the cancer had stopped at one year compared to 10 percent of the women treated with chemotherapy alone. The median time to disease progression was increased by 65 percent (from 4.6 to 7.6 months). Overall, Herceptin significantly increased the likelihood that the cancer would not advance in the women. Adding Herceptin to chemotherapy also increased the number of women who had a partial response or tumor shrinkage (of 50 percent or greater) from 32 percent to 48 percent, a 50 percent increase. Patients who received Herceptin in combination with both drug treatments benefited, but the results were greater for those taking paclitaxel. In the Herceptin plus DC, 52 percent of women had a positive response, compared to 43 percent in patients receiving DC alone. In the Herceptin plus paclitaxel group, 42 percent of women had a positive response, compared to 16 percent in patients receiving paclitaxel alone. The medium duration of response was over nine months in the Herceptin group compared to less than six months in the chemotherapy group alone. Adverse Reactions, Side Effects Herceptin was generally well tolerated among patients in both trials. Overall, the most common adverse reactions related to Herceptin were chills and fever in 40 percent of patients, primarily with the first infusion. Side effects that occur often in women receiving chemotherapy, including hair loss, mouth sores, and low blood cell count levels, were not seen commonly among women taking Herceptin alone. An increased risk of heart dysfunction occurred in women receiving Herceptin and the two drug combination compared to women receiving two drugs alone. In most cases, this side effect can be managed with medication. Most of these patients (87 percent) improved with initial treatment for their heart dysfunction and many continued with their weekly infusion of Herceptin without further cardiac events. HER2 The HER2 growth factor receptor was identified in 1995, and researchers began to understand the role that excess production of HER2 plays in the progression of breast cancer. About a quarter of women with breast cancer have tumors that overexpress HER2. Women with breast cancer have not been routinely screened for HER2 overexpression because there had not previously been a treatment that targets this condition directly. SOURCE Rush Presbyterian-St. Luke's Medical Center CO: Rush Presbyterian- St. Luke's Medical Center ST: Illinois IN: SU: 05/17/98 21:00 EDT prnewswire.com

To: Alper H.YUKSEL who wrote (21010)	5/18/1998 6:06:00 AM
From: Henry Niman	Respond to of 32384

Here's Reuter's on Herceptin: Trials show Herceptin slows spread of breast cancer By Mark Egan LOS ANGELES, May 17 (Reuters) - Human trials of Genentech Inc.'s <GNE.N> drug Herceptin showed it can prevent the spread of metastatic breast cancer by up to three months, cancer researchers said on Sunday. Phase III trials of the drug in human patients, typically one of the final hurdles before approval by the U.S. Food and Drug Administration, showed Herceptin helped stop the spread of cancer and slowed tumor growth in women with metastatic breast cancer when added to chemotherapy. If Herceptin gains FDA approval, as expected later this year, it will become the first monoclonal antibody for the treatment of metastatic breast cancer. A cancer is metastatic when it has spread from the original tumor to other parts of the body. Herceptin works by targeting the HER2/neu protein. About 25 to 30 percent of women with breast cancer "overexpress", or produce too much, of the protein due to a genetic defect. The trial was conducted on 469 women who produced too much of the HER2/neu protein. Dr. Dennis Slamon, director of the Revlon/UCLA Women's Cancer Research program who was a lead scientist on the trial, said Herceptin slowed or stopped the spread of the cancer by up to three months in women with metastatic breast cancer who produced too much HER2/neu protein. Women with metastatic breast cancer who over-produce the protein typically live for 10-18 months once the cancer has become metastatic, he said. Doctors at the American Society of Clinical Oncology's annual meeting here called the drug a medical breakthrough because it is the first breast cancer treatment targeted to attack a specific genetic defect. "This proves the paradigm that if we understand what is broken in the malignant cell we can possibly fix it," said Slamon. "Herceptin is the first successful cancer treatment that targets a specific genetic alteration as opposed to using a shotgun approach that kills both diseased and healthy cells," he added. Herceptin avoids traditional chemotherapy side effects such as hair loss and significant drops in blood counts, he said. When taken with the drugs Adriamycin and Cytoxin, Herceptin showed 50 percent greater breast cancer reduction in 52 percent of patients compared to a 43 percent response in patients who took Adriamycin and Cytoxin alone. When taken with the drug Taxol 42 percent of women had a significant response compared to just 16 percent in patients taking Taxol alone. Overall, Herceptin taken with traditional chemotherapy drugs had a 50 percent better response rate than women who only used usual chemotherapy. Dr. Craig Henderson, who was on a panel to discuss the drug, said that the trial, paid for jointly through public and private funds, was a true pay-off for taxpayers. "The tax payers are getting their money back,' he said. "This is science at its best and most elegant." Another doctor on the panel said he expected "a tidal wave" of future drugs would use a similar approach. Breast cancer is the most prevalent form of cancer in women, with about 180,000 cases diagnosed each year in the United States and 43,500 deaths from breast cancer expected this year. Slamon said Herceptin had the potential to treat other forms of cancer where the HER2/neu protein was overexpressed such as ovarian and gastric cancer. Monoclonal antibodies can recognize antigens on the surface of cancer cells and bind to tumor cells thereby interrupting their biological processes and killing them. Herceptin was made using genetic material from a mouse and then "humanizing" it so the body's immune system would not attack it. Almost 20,000 doctors are attending the ASCO conference to discuss new advances in cancer treatment. Cancer is second only to heart attacks as a cause of death in the United States. About half of those diagnosed do not survive, 1.2 million cases of cancer are diagnosed annually and about 565,000 American are expected to die of the various types of cancer in 1998. 20:21 05-17-98

To: Alper H.YUKSEL who wrote (21010)	5/18/1998 6:08:00 AM
From: Henry Niman	Respond to of 32384

Here's GNE's BLA: Genentech Submits Application for FDA Approval of HER2 Antibody, Herceptin; First Monoclonal Antibody for Treatment of Metastatic Breast Cancer SOUTH SAN FRANCISCO, Calif.--(BW HealthWire)--May 4, 1998-- Genentech, Inc. (NYSE:GNE) today announced completion of its submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for Herceptin(tm) (Trastuzumab), a humanized anti-HER2 monoclonal antibody intended for the treatment of women with metastatic breast cancer who have tumors that overexpress the growth factor receptor, HER2. Herceptin is designated as a Fast Track Product by the FDA and will receive a priority review with a decision anticipated within six months. "This Fast Track Biologics License Application represents a massive effort on the part of Genentech, the clinical trial investigators and staff, breast cancer patient advocates, researchers and the FDA to evaluate this novel treatment as rapidly as possible," said Arthur D. Levinson, Ph.D., Genentech's president and chief executive officer. "Submission of our license application to the FDA brings us another step closer to providing a new therapy which may benefit women with this aggressive form of breast cancer." If Herceptin is approved for marketing, it will be a new biologic approach for the treatment of women with HER2-overexpressing metastatic breast cancer. HER2-overexpression affects 25-30 percent of breast cancer patients and is associated with more rapid cancer progression and shortened survival. Herceptin, the first monoclonal antibody for treatment of breast cancer, has been shown in laboratory studies to slow the growth of human breast cancer cells that overexpress HER2. Genentech's license application to the FDA is based on the results of two recent Phase III clinical trials. The results of these trials will be presented on May 17 at the annual meeting of the American Society of Clinical Oncology (ASCO). The preliminary results of these studies were announced by Genentech in December 1997. Approximately 1.6 million women have been diagnosed with breast cancer in the United States with 180,000 new cases diagnosed in any given year. Genentech estimates that there are approximately 164,000 women with metastatic breast cancer. Of these women, 25-30 percent have tumors that overexpress HER2 and would be candidates for this potential therapy. Genentech, Inc. is a leading biotechnology company that discovers, develops, manufactures and markets human pharmaceuticals for significant unmet medical needs. Eleven of the currently marketed biotechnology products stem from Genentech science, seven of which Genentech markets in the United States. The company has headquarters in South San Francisco, California and is traded on the New York Stock Exchange and Pacific Exchange under the symbol of GNE. CONTACT: Genentech, Inc. Marie Kennedy, 650/225-8751 (Media) Susan Bentley, 650/225-1034 (Investors) gene.com KEYWORD: CALIFORNIA BW0148 MAY 04,1998

To: Alper H.YUKSEL who wrote (21010)	5/18/1998 6:10:00 AM
From: Henry Niman	Respond to of 32384

Here's UPI: Sunday May 17 9:38 PM EDT Researchers discover breast cancer drug UPI SCIENCE NEWS LOS ANGELES, May 17 (UPI) - Cancer researchers have stopped or slowed a fast-working, fatal form of breast cancer in more than half their patients using a so-called ''breakthrough'' drug that short-circuits a gene that may trigger the disease. About a third of all breast cancers involve too many HER2 proteins in breast tissue cells. HER2 appears to be a spark for quick-spreading tumors that usually kill in 12 to 18 months. Scientists at the annual meeting of the American Society of Clinical Oncology in Los Angeles said today that tumors were shrunk or stopped in 53 percent of the 469 women involved in a Phase III trial of the drug. The drug, called a monoclonal antibody, was used with standard chemotherapy on patients with aggressive breast cancer that had already spread around the body. Dr. Dennis Slamon, from the University of California, Los Angeles, who announced the findings said, ''There is even evidence that some patients who initially showed partial responses have converted to complete response.'' Cancer researcher Dr. Craig Henderson of the University of California, San Francisco, cautioned that the drug is not a cure and will have to be used with standard chemotherapy treatments. Henderson added: ''The breakthrough is the conversion for moving from lab to clinic. If you ask me if the tide has turned the answer is an unequivocal 'yes'.'' The HER2 protein is found on the surfaces of cells in the breast and produces a protein that signals the cells to reproduce. In a normal cell there are about 50,000 of these genes, but in the cancerous cells there can be 1.5 million. The monoclonal antibody, Herceptin is made by Genentech, a South San Francisco, Ca., company. Slamon says that because of short supply, the drug is only available now via a computerized lottery run by the National Cancer Institute through its 1800-4-CANCER phone number. The drug has been given a fast-track go-ahead by the Food and Drug Administration and is expected to be available for patients toward the end of the year.

To: Alper H.YUKSEL who wrote (21010)	5/18/1998 6:13:00 AM
From: Henry Niman	Respond to of 32384

Here's ABC news: By Joan Bennett ABCNEWS.com L O SÿÿA N G E L E S, May 17 - Cancer researchers at their annual meeting in Los Angeles say a recent human trial offers new hope to women with breast cancer. ÿÿÿÿ A drug that slows the spread of breast tumors appears to be on the horizon and another researcher is set to try a combonation of drugs. ÿÿÿÿ Cancer researchers say the new drug Herceptin may help prevent the spread of breast cancer by up to three months. ÿÿÿÿ A trial study of 469 women found the drug, when combined with chemotherapy, helped to prevent breast cancer from spreading to other parts of the body. ÿÿÿÿ It also appeared to slow the growth rate of cancerous tumors in the breast. Trials Raise Hopes "This is the biggest difference I've ever seen in a Stage 4 trial-in a trial in advanced breast cancer," said Dr. Larry Norton of Memorial Sloan Kettering Cancer Center. ÿÿÿÿ The drug works by targeting a protein called HER 2, which regulates normal cell growth. About one fourth of women with breast cancer produce an overabundance of that protein, which causes their cancer to grow and spread. ÿÿÿÿ The Food and Drug Administration is expected to finish its review of the drug this year. If it is approved, Herceptin would be the first treatment of its type for breast cancer. ÿÿÿÿ "Herceptin was designated by FDA as a fast track product," said Susan Allman of Genentech. More Good News on Cancer On another front in the cancer war, two new cancer drugs which wiped out tumors in lab mice will be tested on terminally ill cancer patients. ÿÿÿÿ Researcher Dr. Judah Folkman tells the Chicago Tribune he's received approval for tests on about 30 patients. Those drugs-endostatin and angiostatin-work by cutting off the supply of new blood to cancerous tumors-in effect, starving them to death. ÿÿÿÿ And Folkman now says he has recently discovered that one of those drugs- endostatin-apparently also works against leukemia in mice. ÿÿÿÿ Full scale clinical trials-with a larger number of patients-are still a year or more away

To: Alper H.YUKSEL who wrote (21010)	5/18/1998 6:40:00 AM
From: Henry Niman	Respond to of 32384

Here's Bloomberg on Herceptin: Genentech's Herceptin Helps Fight Breast Cancer, Study Shows Bloomberg News May 17, 1998, 4:19 p.m. PT Genentech's Herceptin Helps Fight Breast Cancer, Study Shows Los Angeles, May 17 (Bloomberg) -- Genentech Inc.'s revolutionary new Herceptin drug helps women with advanced breast cancer fight the disease, new research shows. Herceptin increases the time a woman can hold off a worsening of the disease and boosts the chances she'll derive benefit from traditional chemotherapy, according to a study presented today. ''This is the biggest difference I've ever seen'' in these kinds of patients, said Larry Norton, head of cancer medicine at Memorial Sloan-Kettering Cancer Center who played a key role in testing the drug. ''This is a big effect. . . when you have an effect this big you have to use it,'' Norton said during a conference of the American Society of Clinical Oncology. ''There is absolutely no question there's going to be a lot of use once it's available,'' he said. Favorable data on the novel cancer drug confirms the expectations of analysts who have been tracking it. They've been watching for the data because it's part of what the California- based company submitted in its marketing application, filed with the Food and Drug Administration last month. ''This is really a step forward for breast cancer patients,'' said Jon Alsenas, an analyst with Furman Selz. The drug can only be used in women who have a genetic irregularity that makes them susceptible to the treatments -- about 30 percent to 35 percent of breast cancer victims. The irregularity is thought to make them harder to treat with other drugs. The company's trial looked at 469 women who had metastatic breast cancer, meaning their tumors had spread beyond their original location to other places in the body. Tumors Shrank Adding Herceptin to a standard chemotherapy routine staved off progression of the disease for three months longer than the chemotherapy treatment alone, researchers found. That amounted to a 65 percent increase in the time a woman could hope to maintain relatively good health. Additionally, 48 percent of women taking Herceptin with chemotherapy saw their tumors shrink by at least half, while only 32 percent receiving chemotherapy alone responded to the treatment. That means a woman was twice as likely to have a strong improvement if she was also given Herceptin. Herceptin didn't add any significant side effects, and on its own it doesn't cause the side effects common in anti-tumor drugs, such as hair loss, and drops in the levels of vital disease-fighting immune cells. The drug does carry an important potential side effect: It appears to amplify a heart-damaging effect common in one of the potent anti-breast cancer drugs. Still, the heart toxicity is manageable if doctors know to watch for it and in most cases women were able to continue getting the Herceptin treatments, the company and researchers said. A separate study presented today showed Herceptin to be a potent drug when given alone to women with advanced breast cancer who have relapsed following traditional chemotherapy. About 16 percent of women in that trial had their tumors shrunk by at least half by Herceptin treatment alone. ''This really doesn't reflect the human impact of what that 16 percent means,'' Norton said. ''These women who were destined to die probably within six months.'' Researchers at a press conference on the drug said they had experience with a few women who had had their cancer suppressed for years. High-Tech Research Today, cancer experts at the ASCO conference praised the drug as one of the first examples of high-technology research making its way into treatments that can benefit patients today. Herceptin is a member of a new wave of cancer drugs that target tumors in a precise and calculated way. Unlike traditional cancer drugs, which are essentially designed to kill a tumor before they kill a patient, these new drugs act only on cancerous cells. ''It is the promise of biotechnology fulfilled,'' said Steven Shak, senior clinical scientist at Genentech. ''Herceptin is a sparkling jewel of Genentech.'' Called a monoclonal antibody, the drug is made from genetically manipulated antibodies and is attracted to a special protein that lies on the outer coating of a cancer cell. The antibody locates those particular cells and gloms onto them. Herceptin targets a protein receptor for the growth factor HER2. Tumor cells in some women -- about 30 percent - produce unusually large quantities of the receptor, which signals cells to multiply. As a result, the aggressive cancer cells grow quickly, and women who have excess HER2 receptors are less likely to survive their cancer. Herceptin latches on to the receptors, shutting off or at least muffling their commands and preventing the tumor cells from dividing and from growing further. Although the drug is not a cure, it could help women with the disease live longer. Genentech won clearance from the Food and Drug Administration last year to sell its Rituxan drug, which it developed in an agreement with IDEC Pharmaceuticals Inc., which works in a different way. Cancer experts said there's evidence that kind of excess protein could play a role in other cancers including certain lung cancers, ovarian, gastric and prostate cancer. About 1.6 million American women are living with breast cancer, and about 10 percent of them have metastatic or spreading cancer, according to Genentech. The FDA has granted the drug so-called fast-track status for its review of the drug for use in the metastatic cancer, which means the agency could approve Herceptin as early as November. --Kristin Reed in Los Angeles, California through the Washington More News:ÿGNE

To: Alper H.YUKSEL who wrote (21010)	5/18/1998 6:45:00 AM
From: Henry Niman	Respond to of 32384

Herceptin is lead story at MSNBC: Novel therapy targets cancer's rootsBreast-cancer drug gets at underlying cause of diseaseBy Charlene Laino MSNBCMay 17 - A novel gene-based therapy that seeks out and destroys cancerous cells is stopping the spread of the disease in some women with advanced breast cancer, an international team of scientists reported Sunday. Even though its long-term impact on survival is not yet known, some experts are calling the approach a "turning point" in the war against cancer, noting that it marks one of the first times a technique that targets the underlying disease process is moving out of the lab and into the patient setting.ÿ ÿ ÿ ÿ ÿ <Picture> <Picture>ÿ ÿ ÿ ÿ ÿ ÿ ÿ <Picture> <Picture: Special Report>"New Hope: The War on Cancer" <Picture: Special Report>"Breast Cancer" <Picture: MSNBC News>Magic bullet in war against cancer? <Picture: Interactive>Are you at risk for breast cancer? ÿ ÿ ÿ ÿ ÿ ÿ <Picture>ÿ ÿ `We are now beginning to understand what is broken in malignant cells and target the problem with new therapies.' - DR. DENNIS SLAMON UCLA ÿ ÿ ÿ ÿEXPERTS GATHERED at the nation's largest cancer meeting said that even by itself, the new drug, known as Herceptin, brings encouraging news, offering some patients with aggressive breast cancers that have spread to other parts of the body a shot at living longer. Preliminary research suggests Herceptin may be useful for patients with ovarian and gastric cancers as well. ÿ ÿ ÿ ÿMore importantly, though, the so-called biotherapeutic drug represents a whole new class of agents that cancer specialists hope will reach the patient setting in the next decade. Unlike the poisons that are currently the mainstays of cancer therapy - toxic chemotherapies that kill both cancerous and healthy cells - the new molecular biotherapeutics target and interfere with the tumor cells' genetic roots, eventually causing their death. Healthy cells appear to be left untouched. ÿ ÿ ÿ ÿ"The paradigm has been proven," said study head Dr. Dennis Slamon of the University of California, Los Angeles. "We are now beginning to understand what is broken in malignant cells and target the problem with new therapies." ÿ ÿ ÿ ÿThe novel approach targets the so-called HER-2 gene. While everyone has the gene, some people make too many copies due to a genetic flaw traced to as yet unknown environmental causes. ÿ ÿ ÿ ÿAbout a decade ago, Slamon discovered that 25 percent to 30 percent of women with breast cancer have the extra copies, which leads them to have too much of the HER2/neu protein in their bodies. Overexpression of the protein, in turn, causes a particularly aggressive form of the disease marked by rapid progression and shortened survival. <Picture> ÿ ÿ ÿ ÿIn subsequent lab work, Slamon isolated the gene in the test-tube and cloned monoclonal antibodies - missile-seeking destroyers that would target and disable it. "One such antibody, Herceptin, worked - inhibiting and killing the bad cells, but not other, healthy cells," Slamon said. ÿ ÿ ÿ ÿHuman trials bore out the lab results, he reported Sunday. ÿ ÿ ÿ ÿIn a study of 500 breast-cancer patients whose disease had spread, those given chemotherapy alone lived a median of 4.6 months, while those given the chemotherapy plus Herceptin lived a median of 7.6 months, he said. Tumor response rates - defined as an objective decrease in tumor size of 50 percent of more - were up to one-third higher in the Herceptin group, he added. ÿ ÿ ÿ ÿMoreover, some patients who had been given the drug in its earliest trials have survived as long as six years, Slamon said. Patients with the aggressive form of disease that Herceptin targets typically only live 8 to 18 months from diagnosis, he said. ÿ ÿ ÿ ÿPresumably, the drug will work even better when given to women with less advanced disease, he added. ÿ ÿ ÿ ÿ"Unequivocally, we have had a turning point," Dr. Lori Goldstein, moderator of the Herceptin session, said at the annual meeting of the American Society of Clinical Oncology in Los Angeles. ÿ ÿ ÿ ÿDRAWBACKS DO REMAIN ÿ ÿ ÿ ÿBut the drug has its limits, the experts were quick to point it. Only 30 percent of women with breast cancer are candidates for the drug - and in those women it does not always work. ÿ ÿ ÿ ÿNor is it yet on the market. But results of the Phase III study - typically the last step before U.S. Food and Drug Administration approval - presented at the meeting Sunday are so promising that the federal agency has agreed to place the new drug on its fast-track approval process. That means Herceptin, made by Genentech, could be approved by the end of the year, said study head Slamon. ÿ ÿ ÿ ÿThere are side effects. Particularly when used in combination with the chemotherapy drug anthracycline, Herceptin causes serious heart problems in about 15 percent of patients. But in most cases, the heart problems can be controlled with drug therapy, Slamon said. ÿ ÿ ÿ ÿAnd at least for now, Herceptin is used in combination with chemotherapy. And scientists said such a one-two punch will probably remain the treatment of choice for several years to come. ÿ ÿ ÿ ÿ `TIP OF ICEBERG' ÿ ÿ ÿ ÿNevertheless, "this is a critical point, just the tip of iceberg," said Goldstein, a breast cancer researcher at Fox Chase Cancer Center, Philadelphia. Approaches like this show that molecular targeting can effectively fight advancing breast cancer, she said. ÿ ÿ ÿ ÿBreast cancer, the most prevalent form of cancer among women, will strike about 180,300 Americans this year, killing 43,500. ÿ ÿ ÿ ÿIf Herceptin gains FDA approval, it will become the first monoclonal antibody for the treatment of cancer. ÿ ÿ ÿ ÿFor now, Slamon urges all women with breast cancer to be tested for the HER2 gene to determine if they are candidates for the new therapy. There are several tests available, not all of which are reliable, he added, so be sure to ask your doctor about a test that is either DNA- or antibody-based. ÿ ÿ ÿ ÿAnd even while the drug awaits final approval, about 100 women are being accepted into clinical trials every four months. The women are picked via the National Cancer Institute's lottery system, which can be reached at 1-800-4-CANCER. ÿ ÿ ÿ ÿ

To: Alper H.YUKSEL who wrote (21010)	5/18/1998 7:33:00 AM
From: Henry Niman	Respond to of 32384

Here's the ASCO summary: New Agent in Breast Cancer Research The first therapy engineered to target a specific protein defect underlying the malignant progression of cancer has has sailed through phase III clinical testing. Herceptin is awaiting approval as a Fast Track Product by the U.S. Food and Drug Administration, Dennis Slamon, MD, reported Sunday. Herceptin was tested in a phase III investigational trial of 469 women with tumors that over-expressed HER-2. The trial found a 53% increase in tumor response rate among women with metastatic breast cancer treated with Herceptin plus chemotherapy compared to those treated with chemotherapy alone, reported Dr. Slamon, vice-chair of research, UCLA Department of Medicine. Moreover, median time to disease progression was increased 65% among the Herceptin group. None of the women had received previous chemotherapy for their metastatic disease. Two of the study participants remain disease-free five and six years after initiation of Herceptin therapy, Dr. Slamon reported. One has needed no further therapy after an initial 18-week course of Herceptin plus chemotherapy. The other continues to receive Herceptin. Incidence of cardiac dysfunction was higher among patients receiving Herceptin and anthracyclines. However, Dr. Slamon reported that the dysfunction was managed with medication in most cases. "We have a new agent that is effective," said Dr. Slamon, "That we were able to take this from the lab to the clinic in relatively short order is what has everyone excited." The HER-2 growth factor receptor was first identified in 1985. Herceptin was submitted for FDA approval at the beginning of the month. Dr. Slamon predicted that Herceptin will be clinically available by the end of the year, and perhaps within a few months. For now, a National Cancer Institute lottery system makes the drug available to about 100 women per quarter with metastatic disease who have failed two previous treatment regimens. Nearly a third of women with breast cancer have tumors that over-express HER-2. The acquired gene aberration is associated with more rapid cancer progression and shortened survival. "Women with HER-2-negative and HER-2-positive breast cancers are different than women with other breast cancers, and should be considered differently," Dr. Slamon said at a morning press conference sponsored by ASCO, "Breast Cancer Treatment Advances." The success of Herceptin "proves the paradigm that if we understand what's broken in breast cancer, we can target that," he stressed. Other speakers at the press conference echoed Dr. Slamon's enthusiasm. "I think this is the first step into the future, taking us from poisons to specific anti-cancer therapies," said Craig Henderson, MD, UCSF. "This is science at its best and most elegant." "This is a critical point in translational research, and is only the tip of the iceberg," commented Lori J. Goldstein, MD, director, Breast Evaluation Center, Fox Chase Cancer Center. Predicted Laura Hutchins, MD, Arkansas Cancer Research Center: "It's the beginning of a tidal wave. I hope the other [investigational treatments] now in the pipeline turn out to be as successful as this one." Sounding a note of caution was Eric Winer, MD, associate professor, Dana Farber Cancer Institute, Boston. While acknowledging that Herceptin provides new hope, he emphasized the importance of not raising false hopes among desperate patients.

To: Alper H.YUKSEL who wrote (21010)	5/18/1998 7:39:00 AM
From: Henry Niman	Respond to of 32384

Here's an ASCO summary of new cancer treatments: EMBARGOED FOR RELEASE UNTIL TIME OF EACH PRESENTATION, NOT TIME OF PRESS BRIEFING (See times indicated on each attached abstract) CONTACT: On-site: ASCO Annual Meeting News Room (213) 765-4622ASCO Media Information Office (212) 880-5300PRESS BRIEFING MONDAY, MAY 18, 9:30 AM (PDT) NOVEL APPROACHES TO FIGHTING CANCER New Tumor-Targeting Methods Show Promise as Next Generation Cancer Arsenal Los Angeles, CA -- May 18 -The results of six studies examining novel cancer-fighting approaches designed to target cancer cells while potentially leaving healthy cells intact will be discussed today at a press conference entitled "New Directions in Cancer Treatment" at the Annual Meeting of the American Society of Clinical Oncology. These next-generation treatments include early human trials of monoclonal antibodies, anti-angiogenesis agents, cancer vaccines, antisense therapy and gene therapy. "Our investment in cancer research is clearly paying off with a host of exciting new approaches to treating the disease," said Lynn M. Schuchter, MD, of the University of Pennsylvania Cancer Center and moderator of the press conference. "Efforts over the last 15 years to understand the biology of cancer - the cellular, molecular and genetic basis for the disease - are now making their way from the laboratory to the bedside." These novel therapies, which could soon be used with standard chemotherapy, radiation and surgery, may eventually emerge as primary treatments for cancer. The primary categories of biotherapeutic cancer treatments include: Monoclonal antibodies: Monoclonal antibodies are designed to fill a critical gap in the body's immune system. While the human body naturally produces antibodies to identify and fight off infections such as viruses and bacteria, cancer is allowed to spread because the immune system does not recognize cancer cells as harmful. Monoclonal antibodies are being developed to supplement the body's immune system, by recognizing and attacking specific proteins expressed by cancer cells. This therapy shows promise both as a single agent, and, more promising, when attached to a toxin or radioactive agent that serves as the weapon that actually kills the cancer cells. Anti-angiogenesis agents: Tumor growth beyond the size of a pinpoint is dependent on the formation of new blood vessels, a process called angiogenesis. Some of the first human trials of anti-angiogenesis agents are demonstrating the potential to inhibit new blood vessel formation, and thus starve tumors of the blood supply they need to grow and spread. Cancer vaccines: Unlike vaccines that are used to prevent infectious diseases, cancer vaccines are therapeutic, stimulating the body's own immune system to recognize and attack already existing cancer cells. Antisense therapy: Antisense therapy works at the genetic level to stop the process by which cancer-causing proteins are produced by cancerous cells. By introducing strands of RNA (antisense) engineered to match and bind to the replicating DNA (sense) of cancer cells, antisense therapy attempts to block cancer cells from reproducing. Gene therapy: Gene therapy attempts to fix damaged DNA or add new DNA in an attempt to mend faulty genes, or introduce genes that make cancer cells sensitive to drug therapy.

To: Alper H.YUKSEL who wrote (21010)	5/18/1998 7:41:00 AM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

Here's ASCO on Chemoprevention (including LLY's Evista, aka Raloxifene for preventing breast cancer):: EMBARGOED FOR RELEASE UNTIL TIME OF EACH PRESENTATION, NOT TIME OF PRESS BRIEFING (See times indicated on each attached abstract) CONTACT: On-site: ASCO Annual Meeting News Room (213) 765-4622ASCO Media Information Office (212) 880-5300 PRESS BRIEFING SUNDAY, MAY 17, 2:30 PM (PDT) BREAST CANCER PREVENTION STUDIES SHOW PRELIMINARY BUT DRAMATIC RESULTS WITH TAMOXIFEN, RALOXIFENE PROSTATE CANCER DEATHS MAY BE REDUCED BY SCREENING Large, Two-Year Study Shows Raloxifene Prevents Breast Cancer Without Apparent Side Effects First Scientific Presentation of Tamoxifen Prevention Data Canadian Study Provides First Suggestion that Prostate Screening May Save Lives Los Angeles, CA -- May 17 - New studies that may lead to substantially reduced incidence and mortality of the two leading forms of cancer will be discussed today at a press conference examining cancer prevention and early detection at the Annual Meeting of the American Society of Clinical Oncology. Data from studies examining both tamoxifen and raloxifene will be presented for the first time at the ASCO Annual Meeting. The studies have received widespread attention for their apparent ability to prevent the development of breast cancer. Lead researchers from the National Surgical Adjuvant Breast and Bowel Project will officially present the results of their widely-heralded tamoxifen study which found that the drug substantially reduces the risk of breast cancer among women at high risk of developing the disease. In addition, two-year studies of raloxifene, a drug widely used for the treatment of osteoporosis, indicate that breast cancer risk among postmenopausal women with no history of the disease may be lowered without the attendant side-effects of tamoxifen. The raloxifene study will be discussed by the lead authors, including Craig Jordan, MD, who was one of the original developers of tamoxifen. "Another weapon may be added to our arsenal of prevention with preliminary findings that raloxifene prevents breast cancer and may prevent endometrial cancer. Coming on the heels of the recent tamoxifen study, this is very exciting news," said Derek Raghavan, MD, PhD, of the University of Southern California Norris Comprehensive Cancer Center, and moderator of the press conference. "However, these drugs are not for every woman. Before advocating their widespread use, further trials must be conducted to determine if these drugs actually prevent breast cancer, or merely delay it." Another important and potentially controversial study provides the first evidence that prostate cancer screening may significantly decrease deaths from this disease. "It appears that prostate cancer mortality may be significantly reduced by screening and early intervention. However, we still need to know more about whether the study's methodology and patient selection process influenced the results, as this is a highly controversial issue. It would be premature to set national guidelines based on any one study, especially as routine implementation of screening asymptomatic patients will be very expensive to the general community. This is encouraging research that needs to be confirmed," said Dr. Raghavan. Breast and prostate cancers are the most common forms of the disease among women and men, respectively. It is estimated that in 1998 there will be 180,300 new cases of breast cancer and 184,500 new cases of prostate cancer. ÿ EMBARGOED UNTIL MONDAY, MAY 18, 2:00 p.m. PDT PLENARY SESSION, WEST HALL ABSTRACT # 3A ÿ Tamoxifen Reduces Breast Cancer Incidence by 45% in Women at High Risk of Developing the Disease Researchers from the National Surgical Breast and Bowel Project presented the results of a trial examining the breast cancer prevention benefits of tamoxifen. Through almost four years of follow-up, the study demonstrated that the drug reduces the incidence of breast cancer by 45% among women at high risk of the disease. "High risk" was determined by looking at each woman's family history of breast cancer, age, pregnancy history and age at time of menstruation, among other factors. Tamoxifen has been used for the past twenty years to treat breast cancer and prevent its recurrence. Of 13,388 women participating in the trial, 85 women on tamoxifen developed breast cancer, compared to 154 cases in the women assigned to placebo. The study did find an elevated risk of developing endometrial cancer (33 cases on tamoxifen, compared to 14 in placebo); pulmonary embolism (17 versus 6); and thrombosis (30 versus 19). Women under 50, however, experienced no excess risk of side effects. ÿ EMBARGOED UNTIL MONDAY, MAY 18, 2:15 p.m. PDT PLENARY SESSION, WEST HALL ABSTRACT # 3 ÿ Raloxifene Reduces Incidence Of Breast Cancer by 58 - 66% and May Reduce Risk of Endometrial Cancer in Postmenopausal Women A new study indicates that raloxifene, a drug widely used for the treatment of osteoporosis, can substantially reduce the risk of breast cancer in postmenopausal women who are at normal risk for the disease, and may also decrease the risk of endometrial cancer. The findings follow the announcement of the results of a trial of tamoxifen, which found that the drug substantially reduced the risk of developing breast cancer in women at high risk of the disease, while slightly increasing the risk of other health problems, including blood clots and endometrial cancer. The studies presented here indicate that raloxifene does not appear to increase other health risks, including those associated with tamoxifen. It should be noted that these are relatively preliminary findings, and that longer-term studies will be needed to determine the full risks and benefits of the drug. A two-year study of 7,705 postmenopausal women being treated for osteoporosis indicates that women at normal risk for developing breast cancer reduced their risk of developing the disease by approximately 66% with daily use of raloxifene, compared to the control group. Early results also indicate no statistically significant increase in risk of endometrial cancer, a cancer of the lining of the uterus. (Results in this summary reflect updated data) ÿ EMBARGOED UNTIL TUESDAY, MAY 19, 1:00 p.m. PDT TOPICS IN BREAST CANCER ORAL SESSION, WEST HALL ABSTRACT # 466 ÿ [RALOXIFENE - CONT'D.] In a second analysis of the same study - that also included several cases from other studies of raloxifene - researchers found that the risk of developing breast cancer was reduced by 58% in women taking raloxifene, compared to women receiving a placebo. This dramatic reduction was observed in postmenopausal women being treated for osteoporosis who had no history of breast cancer. The researchers conclude that there is substantial evidence for a profound reduction in the risk of developing breast cancer for patients on raloxifene. (Results in this summary reflect updated data) ÿ EMBARGOED UNTIL MONDAY, MAY 18, 2:45 p.m. PDT PLENARY SESSION, WEST HALL ABSTRACT # 4 ÿ Canadian Study is First to Show Screening Reduces Prostate Cancer Deaths An eight-year large-scale randomized study, begun in 1988, was designed to evaluate the survival benefit of prostate cancer screening. The results indicate that screening and early intervention may significantly reduce deaths from prostate cancer. The study randomly divided 46,193 men aged 45 to 80 from the Quebec City electoral roll into those who would be screened and those who would not. Those screened received a PSA (prostate-specific antigen) test and digital rectal examination at the first visit and transrectal echography of the prostate if PSA or digital rectal examination was abnormal. At annual follow-up visits, a PSA test was performed, followed by digital rectal examination and transrectal echography if PSA was abnormal (above 3.0ng/ml, or an increase of more than 20% in one year). 137 deaths due to prostate cancer occurred in the 38,056 unscreened men, while only 5 deaths were observed among the 8,137 screened men, corresponding to 48.7 deaths/100,000 men-years for the unscreened group, and 15.0/100,000 men-years in the screened group, or a 69% decrease in deaths from prostate cancer in the group of men who were screened and received early treatment. The authors conclude that screening based largely on PSA test results is a highly efficient means of diagnosing localized prostate cancer at a reasonable cost, and that it results in an important reduction of cancer death. However, other experts caution that the mechanism of patient recruitment may have biased the study, and confirmatory data will be required before this approach becomes a national standard. (Results in this summary reflect updated data)

To: Alper H.YUKSEL who wrote (21010)	5/18/1998 12:13:00 PM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

Here's Dow Jones on Herceptin: Genentech's Herceptin Popular Topic at ASCO meeting By Otesa Middleton LOS ANGELES (Dow Jones)--More than 5,000 doctors at the American Society of Clinical Ongology annual meeting here turned out to hear San Francisco-based biotechnology company Genentech Inc. (GNE) discuss results of its breast cancer study. Sunday evening, Genentech drew more than a quarter of the conference's almost 19,000 attendees to its presentation on its drug Herceptin, which studies show slows progression of the cancer and shrinks tumors. The company May 4 submitted its application to the U.S. Food and Drug Administration, which designated the drug for fast-track review; that generally means a ruling within six months. Herceptin is designed to treat one aggressive form of breast cancer - in particular, that marked by an increase in production of a protein called HER2. About 25% to 30% of all patients with breast cancer produce a large amount of the protein. "These women had a more aggressive form of the disease," said Dr. Dennis Slamon of the University of California, Los Angeles School of Medicine and principal investigator of Herceptin. "We found it made tumors grow rapidly." In patients with normal HER2, the median survival from the time of diagnosis is six to seven year. For patients with an overabundance of HER2, median survival is just half that. Genentech's Phase III study of Herceptin looked at 469 breast cancer patients who showed an overexpression of HER2. It compared standard chemotherapy alone to standard chemotherapy plus Herceptin, and showed tumors in patients who received Herceptin progressed slower. The median time to progression in patients receiving Herceptin was 7.6 months, compared to 4.6 months for patients who got chemotherapy alone. Of patients who received Herceptin, 49% showed a partial response rate, compared to 32% of patients on chemotherapy alone. Partial response is defined as at least a 50% decrease in tumor size. Genentech also studied Herceptin alone in 222 patients with spreading breast cancer, who showed an overexpression of HER2 and had relapsed after one or two chemotherapy regimens. Of those patients, 16% responded to the treatment. The most common adverse reactions to Herceptin were chills and fever. Hair loss, mouth sores and low blood cell count levels, which occur often in women undergoing chemotherapy, weren't seen commonly among women taking Herceptin alone. Women taking Herceptin and anthracyclines at the same time had an increased risk of cardiac dysfunction. About 180,300 new breast cancer cases are expected in the U.S. this year. Genentech provides Herceptin through a lottery program on an expanded access basis, which allows the company to distribute the drug for free before FDA approval. About 100 women per quarter are chosen to receive the drug through a computerized lottery conducted by the National Cancer Institute. -Otesa Middleton 202-862-6654

To: Alper H.YUKSEL who wrote (21010)	5/20/1998 6:37:00 AM
From: Henry Niman	Respond to of 32384

Here's Reuters on smoking and breast cancer prevention: W A S H I N G T O N, ÿ May 19 - Smoking, one of the biggest causes of cancer and heart disease, may actually help reduce the risk of breast cancer in some women, researchers say. ÿÿÿÿ The finding both surprised and dismayed the international team of scientists who did the study, but they said it may shed light on some of the mechanisms behind breast cancer. ÿÿÿÿ "We would hate it if women started smoking because of this study," Dr. Paul Kleiheus of the World Health Organization, which helped sponsor the study, said in a telephone interview. ÿÿÿÿ The study found that smoking reduces by 50 percent the risk of developing breast cancer in women who have a rare genetic mutation that can lead to to the disease. The mutation, in the genes BRCA1 and BRCA2, affects on average one in 250 women. Study of Lifestyles Kleiheus, who directs WHO's International Agency for Research on Cancer, and colleagues were checking for a variety of lifestyle factors that could affect women with the mutation. It is known that just having a "bad" gene does not guarantee disease-outside factors count, too. ÿÿÿÿ So they were looking for which factors these might be, and surveyed more than 300 women in the United States and Canada who had BRCA1 or BRCA2 mutations. Half, 186 of them, had developed cancer and half had not. ÿÿÿÿ They asked them about various factors, such as when they had children, what they ate-and whether they smoked. ÿÿÿÿ The first thing that jumped out at the researchers was the clear link to smoking. "It was a surprise that smoking was the most striking result," Kleiheus said. ÿÿÿÿ "We are a little bit embarrassed," said Gilbert Lenoir, a biologist at the IARC, who also worked on the study, published in the Journal of the National Cancer Institute. ÿÿÿÿ "We are embarrassed because we feel that the tobacco industry may propagate this without being responsible." Lung Cancer Bigger Killer The researchers point out that many more women in industrialized countries such as the United States die from lung cancer than die from breast cancer. ÿÿÿÿ The American Cancer Society predicts that 80,000 women will develop lung cancer this year and 67,000 will die from it, as compared to 43,500 deaths from breast cancer. ÿÿÿÿ "I think it wouldn't be a good idea to take up the habit," Kleiheus said. "But on the other hand it is important for us, for the scientific community, and for the families that we have some hope for new research to try to come to some preventative measure." ÿÿÿÿ The researchers think there is probably a clear mechanism for explaining why smoking has this effect, and they hope that drugs can emulate the effect. ÿÿÿÿ "If you can inhibit the breast cancer risk in these women by smoking, then you can also do it by other ways," Kleiheus said. "We believe the most likely mechanism is a down-regulation of estrogen metabolism," he added. "This is a known effect of smoking." Stop Estrogen Breakdown In other words, something in tobacco smoke slows down the breakdown of the female hormone estrogen in the body. Breast cancer is known to be linked to estrogen. ÿÿÿÿ Kleiheus said perhaps drugs that interfere with estrogen could be developed to prevent breast cancer. ÿÿÿÿ In fact, they have. Researchers this week said two drugs, the established cancer drug Tamoxifen and the osteoporosis drug raloxifene, sold as Evista, can prevent breast cancer in women. ÿÿÿÿ Both interfere with the way estrogen is used by the body. ÿÿÿÿ Kleiheus said the drugs would have to be tested specifically on women with the BRCA1 and BRCA2 mutations to see if they also worked in this group. ÿÿÿÿ "Indeed they may be the drugs of choice, but we don't know this at moment because no study was done with these two agents in this high-risk population," he said.