From alt.support.mult-sclerosis Tue Oct 11 20:46:13 1994 From: "Ross M. Greenberg" Date: Tue, 11 Oct 1994 14:54:00 EST Newsgroups: alt.support.mult-sclerosis Subject: COP-1/Biogen Betaseron Announcements What follows below are a bunch of articles on the findings from the COP study and from Biogen's once-a-week betaseron. A coupla of PR pieces crept in, but they look as if they're more informative than than the AP/Reuters/UPI stuff. Looks good to me, but then I don't even play a doctor on TV! =================================================== APn 10/11 0321 Multiple Sclerosis Copyright, 1994. The Associated Press. All rights reserved. By MALCOLM RITTER AP Science Writer NEW YORK (AP) -- Two experimental drugs have reduced the frequency of symptom attacks in one kind of multiple sclerosis, and one drug is also the first to delay the progress of long-term disability, researchers say. The work focused on a relapsing kind of MS that affects 75,000 to 140,000 Americans. In all, some 250,000 to 350,000 Americans have MS. People with relapsing MS suffer from bouts of symptoms including abnormal fatigue, impaired vision, loss of balance and muscle coordination, slurred speech, tremors and partial or complete paralysis. Patients recover at least partially during the weeks or months after each episode, but become progressively disabled. Doctors now treat many relapsing MS cases with a drug called interferon beta 1B, or Betaseron, which reduces the frequency and severity of attacks. It was approved by the Food and Drug Administration last year. The new results are welcome because the experimental drugs may provide options, said Stephen Reingold, vice president for research and medical programs at the National Multiple Sclerosis Society. "After so many years of no therapy for MS at all, and following the FDA approval of Betaseron in 1993, here it is fundamentally a year later and there are two new reports of different medications," he said. "From our perspective, this is terrific." Reingold said the new results must be analyzed completely, scrutinized by experts and submitted to the FDA for its evaluation as soon as possible. The work was reported Monday in San Francisco at the annual meeting of the American Neurological Association. One study found that a drug called copolymer I reduced the number of MS attacks. Researchers had 125 patients inject themselves daily with the drug and the other 126 inject themselves with a placebo. Over two years, patients using the drug had a total of 160 MS attacks, versus 210 in the placebo group. In the second year alone, the totals were 59 versus 82, said study coordinator Dr. Kenneth Johnson of the University of Maryland Medical Center. The other study found that a substance called interferon beta-1a can delay increases in chronic disability, as well as reduce the number of attacks, said principal investigator Dr. Lawrence Jacobs. No other drug has delayed the progression of chronic disability, Reingold said. The study was done with 301 patients who had zero to moderate chronic disability. They received weekly injections of either the beta interferon -- which is chemically different from Betaseron -- or a placebo. Researchers tracked chronic disability with a 10-step scale that measured weakness or spasticity in the limbs, double vision, slurred speech and lack of physical coordination. They followed patients over two years to see how many avoided getting worse by a full step on the scale. At the end of two years, 80 percent of patients taking interferon had avoided this progression, versus 65 percent of patients taking the placebo, Jacobs said. He is a neurology professor at the State University of New York at Buffalo and head of neurology at Buffalo General Hospital. About 15 percent of patients taking interferon had three or more MS attacks over the two years, versus about 35 percent of patients taking the placebo, he said. ==================================================================== APn 10/11 0021 Multiple Sclerosis-Findings Copyright, 1994. The Associated Press. All rights reserved. By The Associated Press Key findings: -- One experimental drug reduced the number of multiple sclerosis attacks by 24 percent over two years. -- Another reduced the progression of chronic disability during the study period. ============================================================= RTw 10/10 2118 New drug delays progression of multiple sclerosis By Gail Fitzer-Schiller LOS ANGELES, Oct 10 (Reuter) - A new drug delayed the progression of multiple sclerosis by 2.3 years and reduced the number of annual flare-ups of the central nervous system disease by 31 percent in a clinical trial, researchers said on Monday. They presented the findings for Biogen Inc's beta interferon drug at a meeting of the American Neurological Association in San Francisco. Researchers reported that another drug tested in clinical trials, Copolymer-1 or Copaxone, reduced the number of attacks in multiple sclerosis (MS) patients in the study by 24 percent and also showed statistical significance in slowing disability. Copolymer-1 is made by Israel-based Teva Pharmaceutical Industries Ltd. Dr Kenneth Johnson, chairman of the University of Maryland medical school's neurology department, said in an interview that 32 percent of MS patients on Copolymer-1 experienced increased disability compared with 46 percent of patients taking a placebo. The potential to slow disability, or the progression of MS, is considered the key to developing a blockbuster MS drug. The only significant MS drug on the market, Chiron Corp's betaserson, reduced flare-ups during its clinical trials but failed to show it can slow the disease. Biogen's lead researcher, Dr Lawrence Jacobs, professor of neurology at the State University of New York at Buffalo, said it took MS patients on beta interferon a median time of 5.4 years to suffer disease progression compared to 3.08 years for patients taking a placebo. "That means you've delayed or prevented them from progressing for 2.3 years...You've extended the time to increased disability by 77 percent," Jacobs said. He said in an interview that patients in the placebo group were twice as likely as patients on beta interferon to experience three or more MS attacks during the two-year trial. In addition, beta interferon produced a twofold decline in the number and volume of active brain lesions caused by MS as measured by magnetic resonance imaging tests, Jacobs said. REUTER ====================================================================== APn 10/10 1917 Multiple Sclerosis Copyright, 1994. The Associated Press. All rights reserved. By MALCOLM RITTER AP Science Writer NEW YORK (AP) -- Researchers using an experimental drug have succeeded for the first time in slowing the progression of a type of multiple sclerosis in which unpredictable attacks leave victims increasingly disabled. The medication, like another experimental drug discussed on Monday at the annual meeting of the American Neurological Association in San Francisco, also reduces the number of MS attacks. The drugs are aimed at a relapsing kind of MS that affects some 75,000 to 140,000 Americans. In all, some 250,000 to 350,000 Americans have MS. People with relapsing MS suffer bouts of symptoms, including fatigue, impaired vision, loss of balance and coordination, slurred speech, tremors and partial or complete paralysis. Patients recover at least partially during the weeks or months after each episode but become progressively disabled. Doctors now treat many people with relapsing MS with a drug called interferon beta 1B, or Betaseron. This drug, approved by the Food and Drug Adminstration just last year, reduces the frequency and severity of attacks. The new results are welcome because the experimental drugs may provide options, said Stephen Reingold, vice president for research and medical programs at the National Multiple Sclerosis Society. "From our perspective, this is terrific," he said, adding that the new results must be analyzed completely, published for scrutiny by experts and submitted to the FDA for evaluation as soon as possible. One study found that a drug called copolymer I reduced the number of MS attacks. Researchers had 125 patients inject themselves daily with the drug, and 126 inject tjemselves with a placebo. Over two years, patients using the drug had a total of 160 MS attacks, compared with 210 in the placebo group. The other study found that a substance called interferon beta-1a can prevent or delay increases in long-term symptoms, as well as reduce the number of attacks, said principal investigator Dr. Lawrence Jacobs. No previous drug has shown an ability to delay the progression of symptoms over the long term, Reingold said. The study was done with 301 patients who had zero to moderate symptoms between attacks. They received weekly injections of either the beta interferon -- which is different from Betaseron -- or a placebo. Researchers measured the progression of the disability with a 10-step scale that looked at weakness or spasticity in the limbs, double vision, slurred speech and lack of coordination. They followed patients over two years to see how many avoided getting worse by a full step on the scale. At the end of two years, 80 percent of patients taking interferon had avoided this progression, versus 65 percent of patients taking the placebo, Jacobs said. He is a professor of neurology at the State University of New York at Buffalo and head of neurology at Buffalo General Hospital. Analysis also showed that about 15 percent of patients taking interferon had three or more MS attacks over the two years, compared with about 35 percent of patients taking a placebo, he said. Dr. Kenneth Johnson of the University of Maryland Medical Center, coordinator of the copolymer I study, said that drug also showed a small effect on the progression of the disability. But Reingold said the result was not convincing. ============================================== OTC 10/10 1903 shows positive results from a Phase III Trial in ... SAN FRANCISCO (Oct. 10) BUSINESS WIRE -Oct. 10, 1994--Copolymer-1, a novel agent being developed by TEVA Pharmaceutical Industries for use in exacerbating-remitting multiple sclerosis (ER-MS), was found to significantly reduce relapse rate, according to data presented here today to the American Neurological Association by Kenneth P. Dr. Johnson, M.D., professor and chairman, Department of Neurology, University of Maryland School of Medicine, and principal investigator in the study. Dr. Johnson reported that patients treated with copolymer-1 experienced 24% fewer relapses than the patients treated with placebo over the two-year study. The results of this copolymer-1 study are of particular interest to neurologists and MS patients not only because of the efficacy data, but also because of the specific way in which copolymer-1 appears to affect the disease process, probably leading to the lower level of reported side effects. "These promising findings confirmed our hopes of developing an entirely new treatment for this devastating disease," said Dr. Johnson, who reported on behalf of the 11 trial sites who participated in this multi-center study. Dr. Johnson reported that in a double-blind placebo-controlled Phase III clinical trial, a total of 251 patients were randomized to receive either placebo or treatment with copolymer-1. The primary endpoint of the trial was a reduction in the number of relapses over two years. Patients in the treatment group experienced an average of 1.37 relapses in two years, compared to 1.74 in the placebo group, which is a statistically significant reduction in relapse rate. Dr. Johnson noted that MS patients with the lowest score (0-2) on the Kurtzke Expanded Disability Status Scale (EDSS), a standard MS disability index, had a greater reduction (up to 34%) in relapse rate than patients with higher initial EDSS levels. Dr. Johnson stated, "We feel that it is important to intervene early in the disease courses especially if the patients can tolerate the drug well over the long-term." Dr. Johnson also observed that there was an increasing difference over time in the number of relapses with a 21% decrease in the number of relapses in treated versus untreated patients in the first six months of the study and a greater reduction of 30% in the last six months of the study. "Although the study was not designed to measure disability as a primary endpoint," Dr. Johnson continued, "we did evaluate patients for changing disability and found that 46% of patients in the placebo group advanced by 0.5 or more on the EDSS scale, while only 32% of copolymer patients did so by the end of the study." This difference reached statistical significance in favor of copolymer-1. "Overall, these data are encouraging in that we may have a completely new agent with a different mechanism of action with which to treat this difficult disease," Dr. Johnson said. "It is especially important to find early therapeutic interventions since the reduction in number of relapses may be associated with affecting the natural course of MS in many patients." Although the mechanism of action of copolymer-1 has not been fully elucidated, laboratory experiments indicate that the effects of copolymer-1 may be disease-specific. In animal models, copolymer-1 seems to intervene specifically to help stop destruction of the myelin sheath. Importantly, copolymer-1 is different than other non-specific immunologic therapies which may induce generalized changes in the immune system. Side effects with copolymer-1 were primarily minor localized injection site reactions. A brief systemic post-injection reaction of flushing or chest tightness and dyspnea, palpitations and anxiety developed at least once in 16% of copolymer-1 patients and in 5% of placebo patients, but caused only 2% of patients to drop out of the study. In all these patients, the reaction resolved quickly with no lasting effects. Dr. Johnson commented that copolymer-1 appeared to be well-tolerated with a minimal side-effect profile. Reacting to Dr. Johnson's report today, Dr. Stephens Reingold, vice president of research and medical programs of the National Multiple Sclerosis Society said, "The National Multiple Sclerosis Society is highly encouraged by these promising results that may lead to the development of an additional treatment for relapsing-remitting MS." In light of the study's results, TEVA intends to commence international registration procedures as early as possible in 1995. Copolymer-1 was discovered at the Weizmann Institute of Science in Israel, clinically investigated at various leading medical centers in Israel and studied at the Albert Einstein College of Medicine in New York City with the results of the latter published in 1987 in The New England Journal of Medicine. In the United States, copolymer-1 is being made available to the ER-MS patients in a Treatment-IND program which allows patients to obtain this promising investigational New Drug in various centers across the country. Additionally, copolymer-1 is being studied in further clinical trials in Europe and Israel. Copolymer-1 is designated as an Orphan Drug by the U.S. Food and Drug Administration. Teva Pharmaceutical Industries Ltd. develops, manufactures and markets human pharmaceuticals, bulk pharmaceutical chemicals, medical disposables and veterinary products. The largest supplier of such products to Israel's public and private healthcare markets, the company has manufacturing facilities in Israel, Western Europe and the United States and over 60% of its sales are generated outside Israel. Teva Pharmaceuticals USA Inc., based in Kulpsville, Penn., incorporates the activities of Gate Pharmaceuticals which was created in 1990 by Lemmon Company. Lemmon Company, one of the nation's largest suppliers of generic drugs, has been a subsidiary of Teva in Israel since 1985. The new U.S. subsidiary will have access to research and manufacturing facilities worldwide and will continue collaborations with leading research institutions such as the Weizmann Institute in a number of central nervous systems and autoimmune diseases. --30--lmm/sf ik/sf jgs/sf CONTACT: Brown and Powers Lisa Weiss or Joyce Yaeger, 212/223-8200 At the Hyatt Regency S.F. 10/10 - 10/12: 415/788-1234 Teva Pharmaceuticals USA Inc., Kulpsville William A. Fletcher, 215/256-8400 Morgen-Walke Associates Donna Stein or Lisa Carlton, 212/850-5600 KEYWORD: PENNSYLVANIA CALIFORNIA INDUSTRY KEYWORD: MEDICINE PHARMACEUTICAL REPEATS: New York 212-575-8822 or 800-221-2462; Boston 617-330-5311 or 800-225-2030; SF 415-986-4422 or 800-227-0845; LA 310-820-9473 =================================================================== UPn 10/10 1851 Drug Slows MS Progression By LIDIA WASOWICZ UPI Science Writer SAN FRANCISCO, Oct. 10 (UPI) -- A promising, although still experimental, drug appears to be the first to slow the progression to disability in multiple sclerosis, researchers said Monday. "To the best of our knowledge, this is the first instance in which a drug has resulted in a delay of the sustained progression to disability in multiple sclerosis under the rigor of phase III research," head researcher Dr. Lawrence Jacobs, professor of neurology at State University of New York at Buffalo, head of the Department of Neurology at The Buffalo General Hospital and chief of the William C. Baird Multiple Sclerosis Center at Millard Fillmore Hospital, Buffalo, said in an interview. "This is very good news for patients with MS in the disability range and shows we are headed in the right direction. While several years ago, there was no treatment, now there is the realistic possibility of a treatment." Researchers cautioned the drug is not a cure and, once approved for clinical use, would probably be used in conjunction with other therapies. The multi-center study indicated patients taking the drug, recombinant interferon beta, INF-B-1a, progressed more slowly to disability and had fewer neurological flareups of the disease than those simply given a placebo. "While previous research has shown beta interferon can reduce the flareups of MS, it had not shown an effect on the progression to disability, and this is really important," said Jacobs, who reported the findings at the annual meeting of the American Neurological Association. Even if the flareups are controlled, the patient still can progress to a disabling condition such as limp limbs or walking problems that require the use of a cane, he noted. Of the 301 study subjects -- primarily white women, the most common sufferers of MS -- 158 were injected intramuscularly with small doses of the drug once a week for up to two years. The other 143 subjects were given a placebo. The MS patients ranged from no disability to moderate disability. In MS, an autoimmune disease that afflicts up to 350,000 Americans and a million people worldwide, cells of the immune system turn their potent chemical weapons against the myelin sheath that protects nerve fibers in the spinal cord and brain. While the severity of the disease varies widely, the resulting nerve damage can cause progressive disability that, after 20 years, leaves 30 percent of patients in wheelchairs. Some 30 percent of patients suffer a mild or moderate form of the disease, characterized by months of quiescence interrupted by relapses. In the trial, sponsored by the National Institutes of Health and Biogen, Inc., a Cambridge, Mass., biotechnology company, recombinant interferon beta increased the time to progression of disability by 75 percent. The researchers also found a 31 percent reduction in the relapse rate among patients experiencing the painful and debilitating exacerbations that characterize the disease and a significant reduction in the number of active brain lesions measured by Magnetic Resonance Imaging. Finally, the researchers observed only minor side effects, such as flu-like symptoms of fever, fatigue and aches. Only 9 percent of the patients receiving the drug stopped treatment, half of them due to side effects. The study was conducted at four clinical centers: the Baird MS Center, University at Buffalo, N.Y.; Mellen MS Center, Cleveland Clinic, Cleveland, Ohio; University of Oregon, Portland, Ore., and Walter Reed Army Medical Center-Georgetown University, Washington, D.C. ========================================================================== OTC 10/10 1536 FIRST DRUG TO SLOW PROGRESSION OF DISABILITY IN ... PHASE III MULTIPLE SCLEROSIS TRIAL OF BIOGEN'S INTERFERON BETA-1a SHOWS 75% EXTENSION IN PREDICTED TIME TO DISABILITY AND ONE-THIRD REDUCTION IN EXACERBATION RATE /ADVANCE/ SAN FRANCISCO, Oct. 10 /PRNewswire/ -- Multiple sclerosis patients in a Phase III clinical trial of recombinant interferon beta (INF-B-1a) progressed more slowly to disability and had fewer neurological flare-ups of the disease than patients on placebo, according to data presented here today by Lawrence Jacobs, M.D., the principal investigator. This is the first time a drug in a blinded clinical trial slowed the progression of disability in multiple sclerosis. Dr. Jacobs presented the data at the annual meeting of the American Neurological Association. He is a professor of neurology at the University at Buffalo; head, Department of Neurology, The Buffalo General Hospital; and chief, Baird Multiple Sclerosis Center. The trial was sponsored by the National Institutes of Health and Biogen, a biotechnology company in Cambridge, Massachusetts. Patients with active relapsing multiple sclerosis experience an uneven pattern of disease progression, characterized by periods of stability interrupted by flare-ups of the disease, after which the patient returns to a new baseline of functioning. In the study, recombinant interferon beta increased the time to progression of disability -- the length of the period during which active relapsing patients sustain a particular baseline -- by 75 percent. The trial also showed a 31 percent reduction in relapse rate among patients experiencing the painful and debilitating exacerbations that characterize the disease, and showed a significant reduction in the number of active brain lesions measured by Magnetic Resonance Imaging (MRI). Biogen's recombinant interferon beta is a genetically engineered drug identical to the natural molecule that occurs in humans and acts both as an antiviral and an immunomodulatory agent. It is administered intramuscularly once a week. The trial was the first blinded study to be done on a recombinant interferon identical to natural beta interferon and the first to demonstrate a statistically significant impact on the progression rate of the disease. Time To Progression Of Disability Increased By 75 Percent The study showed that recombinant interferon beta lengthens the time for the disease to become more disabling, demonstrating a 75 percent increase in the projected time it takes for the disease to progress one unit on the Kurtzke Expanded Disability Status Scale (EDSS), a standard measure of disability progression in multiple sclerosis. At the end of one year of treatment, 20.1 percent of placebo-treated patients had progressed by 1.0 EDSS units, compared to 12 percent of patients on recombinant interferon beta. At two years, 36.3 percent of placebo patients had progressed, compared to 22.6 percent of treated patients. Based on an analysis of the data, predictions of median time to progression by 1.0 EDSS units were 3.1 years for placebo patients and 5.4 years for treated patients. Exacerbation Rate Reduced By One-Third Patients receiving recombinant interferon beta had approximately one-third fewer exacerbations (0.62 disease flare-ups per year) than patients receiving placebo (0.9 exacerbations per year). This represents a 31 percent reduction in relapse rate among treated patients. Placebo patients were twice as likely to have three or more attacks during the study as were treated patients. MRI Data Shows Statistically Significant Drop In "Active" Brain Lesions Data from MRI studies, which are used as markers of how far and how fast the disease is spreading, showed a statistically significant reduction in the number and volume of active lesions in treated patients compared to placebo patients. An approximately two-fold difference in the mean number and volume of such lesions was noted. No discernible effects were seen on T2 lesion volume, a measure of both active and inactive lesions. Modest Side Effects and Minimal Injection-Site Reactions Only modest side effects were seen in the study. They included occasional and transient flu-like symptoms (fever, fatigue and achiness). Treated patients experience flu-like symptoms an average of eight days over two years, as compared to two days among the placebo group. Injection-site reactions were minimal and not different between groups treated with study drug and placebo. Nine percent of recombinant interferon beta patients stopped treatment, half of which were attributed to side effects. Study Design The study, which began in 1990, involved 301 men and women with active relapsing multiple sclerosis who received either recombinant interferon beta or placebo intramuscularly once a week for periods up to two years. The definition of "active relapsing" MS included patients with both relapsing-remitting and relapsing-progressive forms of the disease. The primary endpoint was time to progression of disability, defined as an increase in the EDSS of 1.0 point above that on entry and persisting for at least six months. Secondary endpoints included the frequency of exacerbations and proportion of patients who were exacerbation-free at two years, as well as studies of MRI data and side effects. The study was conducted at four clinical centers in the United States: the Baird MS Center, University at Buffalo, N.Y.; Mellen MS Center, Cleveland Clinic, Cleveland, Ohio; University of Oregon, Portland, Ore., and Walter Reed Army Medical Center/Georgetown University, Washington, D.C. The MRI scores all were analyzed at one laboratory at the University of Colorado, Denver, Colo. Multiple sclerosis is a progressive neurological disease in which the body loses the ability to transmit messages among nerve cells, leading to loss of muscle control, paralysis and, in some cases, death. It affects between 250,000 to 350,000 Americans and is believed to affect more than 1 million people worldwide. Although it was first diagnosed more than 100 years ago, there is no prevention or cure for the disease. More than 10,000 Americans are diagnosed with MS each year. After epilepsy, it is the second most common chronic neurologic disease of young adults. Onset is unusual before adolescence, then rises in frequency from the teenage year to age 35, and declines gradually thereafter. It is approximately twice as frequent in women as in men. More than 100,000 patients in the U.S. suffer from the relapsing form of the disease characterized by acute attacks, followed by partial or complete remission. Recombinant interferon beta is still an investigational drug and is not available on the market. Earlier this year, Biogen announced plans to file for licensure in the United States and regulatory approval in Europe in the first half of 1995. -0- 10/10/94/1830 /CONTACT: Mike Shaw, director of public relations of The Buffalo General Hospital, 415-788-1234 (Oct. 10-11 only) or 716-845-2041; Lois Baker, news bureau of University of Buffalo, 716-645-6067; or Christine Hinz of GTFH Public Relations, 212-886-3084, or (Oct. 10 only) 415-788-1234/ (BGEN) CO: Biogen Inc.; National Institutes of Health ST: California IN: MTC SU: - -- Ross M. Greenberg Virus Acres 914-586-2023 greenber@ramnet.com New Kingston, NY 12459 Fax: 914-586-2025 For info on RamNet: send mail to ramnet@ramnet.com DOS<==>UNIX autoreply