To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: Investigational Alzheimer's Drug, Reminyl (Galantamine), Improves Memory And Behavior URL: http://www.pslgroup.com/dg/195B32.htm Doctor's Guide April 7, 2000
STOCKHOLM, SWEDEN -- April 7, 2000 -- Patients treated with Reminyl(R) (galantamine) -- a new treatment being studied for Alzheimer's disease by Janssen Pharmaceutica Products, LP -- improved in memory, behavior and ability to perform activities of daily living, a new five-month study has found. In addition, a second study presented suggested that the cognitive and functional benefits of galantamine may be sustained for at least 12 months. The data from the five-month study is being shared for the first time at the 6th International Springfield Symposium, a Stockholm meeting of leading Alzheimer's experts. Galantamine is being developed by Janssen Pharmaceutica under a co-development and licensing agreement with UK-based Shire Pharmaceuticals Group, plc. A new drug application for galantamine has been filed by Janssen and is now under review by the U.S. Food and Drug Administration (FDA). The first study was a five-month, double-blind, placebo-controlled trial involving 978 patients with mild to moderate Alzheimer's disease. Participants were randomized to four different treatment arms: a group that received placebo and three that took daily doses of galantamine of 8 mg, 16 mg or 24 mg, respectively. Efficacy was assessed using a variety of measures, including the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-cog), which measures a patient's memory, language and orientation; the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), which provides an overall assessment of patient functioning -- including behavior, psychiatric symptoms, cognition and activities of daily living; the version of the Alzheimer's Disease Cooperative Study Inventory that includes activities of daily living (ADCS-ADL); and the Neuropsychiatric Inventory (NPI), which evaluates the frequency and severity of 10 types of behavioral symptoms, such as anxiety, apathy and disinhibition. "Contrary to common belief, there are a number of devastating consequences of Alzheimer's disease other than memory loss -- such as severe restlessness, lack of impulse control and deterioration in activities of daily living, which include basic functions such as bathing and dressing," says Pierre Tariot, MD, a galantamine investigator and professor of psychiatry, medicine and neurology at the University of Rochester Medical Center, New York. Overall, the patient group treated with the proposed 16 mg maintenance dose of galantamine (which is under review by the FDA) scored higher on each efficacy measure than study participants who received placebo. The scores that measure cognition and the frequency and severity of behavioral symptoms were improved in the galantamine group at the completion of the study, compared to when the patients began the trial. In contrast, the scores for the group taking placebo had worsened. Likewise, the ability to perform activities of daily living was virtually unchanged from the start of the trial among the galantamine-treated group, whereas it deteriorated among the patients who took placebo. Similar efficacy was observed in the group that received 24 mg of galantamine daily. Adverse effects experienced by study participants were mostly gastrointestinal in nature, and were reported as mild and transient. The discontinuation rate due to adverse effects was similar between the group taking the proposed galantamine maintenance dose of 16 mg and those receiving placebo (7 percent for both groups). The number of patients reporting any serious adverse effects was similar for both patients taking 16 mg of galantamine and those receiving placebo (10 vs. 11 percent respectively). Side effects that were reported at least 5 percent more often by patients taking galantamine as by those receiving placebo included nausea and diarrhea (13 vs. 5 percent and 12 vs. 6 percent, respectively). A similar safety profile was observed in the group taking 24 mg of galantamine daily. The long-term data were derived from a second study, in which 636 patients were first randomized into three groups for six months, receiving either placebo or a maximum daily galantamine dose of 24 mg or 32 mg. The second phase of the trial was an open-label extension, in which 81 percent of the participants who completed the first six months of the study continued treatment with a daily, 24 mg dose of galantamine for an additional six months. Primary measurement tools included the ADAS-cog and CIBIC-plus scales. On average, among the group treated with galantamine, cognitive performance and the ability to participate in activities of daily living were equal to or above baseline after one year of treatment. This is the first time in which any Alzheimer's drug has been reported to sustain cognitive and functional benefits in individuals with the disease for 12 months. "Normally, an individual with Alzheimer's disease would be expected to decline significantly over the course of a year," says Tom Wessel, MD, the Janssen Research Foundation's global medical leader for the development of galantamine. "The results from this study suggest that galantamine may stabilize patients for at least a year." As with the shorter-term trial, side effects experienced by study participants who received galantamine were mostly GI in nature, transient and mild to moderate in intensity. Similar to other therapies currently on the market, galantamine inhibits an enzyme called acetylcholinesterase that breaks down acetylcholine -- a critical neurotransmitter that plays a key role in memory and learning. Decreased levels of acetylcholine have long been considered a significant contributor to the symptoms of Alzheimer's disease. However -- unlike other agents -- research suggests that galantamine may also indirectly act on the brain's nicotinic receptors, to which acetylcholine binds. Laboratory research suggests that galantamine increases these receptors' sensitivity to acetylcholine, and in turn stimulates its release (1,2,3). The clinical significance of this finding is not yet known, but is being investigated further by Janssen. An estimated four million Americans have Alzheimer's disease today, but that number is expected to change dramatically. "Alzheimer's disease is growing exponentially as the population ages; it has been projected by the Alzheimer's Association that the number of Americans with the disease will grow by 100 percent by 2030, and by 350 percent in 2050," notes Dr. Wessel. "Doctors, patients and their families need new treatment options." Reminyl (galantamine) is being developed by the Janssen Research Foundation, under a co-development agreement with UK-based Shire Pharmaceuticals Group plc. It was recently approved in Sweden, and is currently being considered by other countries as part of the European Union Mutual Recognition Procedure. A New Drug Application (NDA) was filed with the U.S. Food and Drug Administration (FDA) in September 1999. If approved by the respective regulatory agencies, galantamine will be marketed under the trade name Reminyl(R) by Janssen Pharmaceutica in the United States, by Janssen-Ortho in Canada and by Janssen-Cilag elsewhere -- with the exception of the United Kingdom and Ireland, where it will be sold by Shire under a co-promotion agreement with Janssen-Cilag. Janssen Pharmaceutica and its affiliate, the Janssen Research Foundation, are headquartered in Beerse, Belgium, and have operating companies in 32 countries, including the United States. A wholly owned subsidiary of Johnson & Johnson, it is a leader in central nervous system research. Other areas of research include analgesia, oncology, gastroenterology and mycology. Shire Pharmaceuticals Group plc is an emerging pharmaceutical company focused primarily on two therapeutic areas: central nervous system disorders and metabolic bone disease, with sales, marketing and R&D operations in the UK and United States. References: 1. Schrattenholz A et al. Agonist Responses of Neuronal Nicotinic Acetylcholine Receptors are Potentiated by a Novel Class of Allosterically Acting Ligands. Molecular Pharmacology. 1996; 49:1-6 2. Maelicke A. Nicotinic Receptors in the Central Nervous System. 6th International Conference on Alzheimer's Disease and Related Disorders. July 18, 1998; Amsterdam, The Netherlands 3. Vidal, C. Nicotinic Receptors in the Brain: Molecular Biology, Function, and Therapeutics. Molecular and Chemical Neuropathology. 1996;28:3-11 Related links: Reminyl, Shire Pharmaceuticals, plc. --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. 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