Eisai and Pfizer: ARICEPT(R) (donepezil HCl) Maintains Functional Ability in The Majority of Alzheimer's Disease Patients on Therapy for One Year

LONDON (PROTEXT) - New Data from a One-Year U.S. StudyReinforces European Findings ARICEPT(R) (donepezil HCl) treatment significantly extends thefunctional ability of patients with mild to moderate Alzheimer'sdisease, according to new one-year data presented today at the12th European College of Neuropsychopharmacology (ECNP) Congress.ARICEPT is a clinically proven, once-a-day prescriptionmedication that is indicated for symptomatic treatment of mild tomoderately severe Alzheimer's dementia. Results of this studyconfirm that treatment with the medication for up to one yearallows patients to maintain their ability to perform activitiesof daily living such as dressing, eating meals, doing chores andenjoying hobbies, and therefore helps them maintain theirindependence. "This is the first U.S. study of acetylcholinesteraseinhibitors to evaluate the effects of one years' therapy inpatients with Alzheimer's disease," said Richard Mohs, Ph.D.,professor, department of psychiatry, Mount Sinai School ofMedicine and the study's lead investigator. "These findingssuggest that prolonged treatment with ARICEPT(R) (donepezil HCl)is an important weapon to improve or maintain patients'independence while living with the disease." During the double-blind, placebo-controlled study, researchersevaluated the time to reach clinically significant decline infunction in patients with Alzheimer's disease taking ARICEPT(R)compared to placebo. Patients who met predetermined criteria forclinically significant decline in function were discontinued fromthe study. These criteria included a decline in the patient'sability to perform one or more basic activities of daily living;a reduction of 20 percent in ability to perform one or moreinstrumental activities of daily living, such as preparing mealsand using household appliances; or a one-point increase in theglobal Clinical Dementia Rating, a clinically validated measureof disease severity. Of the 431 patients, 214 took 10-mg ofARICEPT(R) once daily, and the other 217 participants tookplacebo. Assessments of patient function were conducted atbaseline and at six-week intervals for 54 weeks. At 48 weeks, patients taking ARICEPT(R) had a 51 percentprobability of maintaining function compared to a 35 percentprobability for those on placebo. In addition, patients onARICEPT(R) maintained their functional ability for about fivemonths longer (median time) than those on placebo. This meansthat ARICEPT(R)-treated patients showed a 62 percent chance ofmaintaining their functional ability over that of patients onplacebo in this one-year study. "The study shows that time to functional loss is delayed inpatients who are treated with ARICEPT(R)," Dr. Mohs added. "Ourresults complement an earlier one-year European trial and providepowerful evidence that ARICEPT(R) is effective in treatingsymptoms in patients with Alzheimer's disease." The new findings reinforce data from the one-year Nordic Studypresented at the Ninth Congress of the InternationalPsychogeriatric Association in August. Results of thatrandomized, double-blind, placebo-controlled trial demonstratedthat ARICEPT(R) (donepezil HCl) had beneficial effects on globaland cognitive functioning and activities of daily living of studypatients treated for one year. These are the first one-yearplacebo-controlled trials in Alzheimer's disease with acholinesterase inhibitor. Alzheimer's disease is a progressive, degenerative braindisorder that results in impaired memory and thinking, behaviorchanges, and loss of language and motor skills. Currently,approximately 15 million people suffer from the disorderworldwide. ARICEPT(R) is indicated for symptomatic treatment of mild tomoderately severe Alzheimer's dementia. ARICEPT(R) is well-tolerated, with a low incidence of side effects, offersconvenient once-daily dosing and can be taken with or withoutfood. In controlled trials that supported the U.S. Food and DrugAdministration marketing approval of ARICEPT(R), it was foundthat the drug's most common side effects include nausea,diarrhea, insomnia, vomiting, muscle cramps, fatigue andanorexia. These effects were often mild, transient and resolvedwith continued treatment. People at risk for ulcers should informtheir doctor when taking ARICEPT(R). In pivotal clinical trials,syncopal episodes have been reported in patients takingARICEPT(R) (2 percent vs. 1 percent for placebo). ARICEPT(R) isclinically effective at the starting dose of 5-mg/day and thedose can be escalated to 10-mg/day after four to six weeks ifclinically indicated. Currently, ARICEPT(R) is available by prescription in morethan 39 countries. In November 1994, Eisai Co., Ltd. and PfizerInc announced the formation of a strategic alliance for thepromotion of ARICEPT(R) and development of new treatments forAlzheimer's disease and other cognitive disorders. First launchedin the United States in February 1997, ARICEPT(R) (donepezil HCl)has been well-received in the Alzheimer's disease community withmore than 232 million days of patient use worldwide (as of June1999). Pfizer Inc, with headquarters in New York, is a research-basedpharmaceutical company with global operations. In 1998 thecompany reported sales of $13.5 billion, and invested more than$2.3 billion in research and development. Eisai Co., Ltd. is a research-based human health care companywhich discovers, develops and markets products in more than 30countries. Through its global network of research facilities,manufacturing sites and marketing subsidiaries, Eisai activelyparticipates in all aspects of the worldwide health care systems.The company reported sales of $2.5 billion in 1997 withapproximately 15 percent of sales spent for research anddevelopment. ARICEPT(R) U.K. prescribing information follows. ARICEPT(R) U.S. prescribing information is available uponrequest. Brief Prescribing Information ARICEPT(R) (donepezil hydrochloride) Please refer to the SmPC before prescribing ARICEPT 5mg orARICEPT 10 mg. Indication: Symptomatic treatment of mild tomoderately severe Alzheimer's dementia. Dose and administration:Adults/elderly; 5mg daily which may be increased to 10mg oncedaily after at least one month. No dose adjustment necessary forpatients with renal or mild-moderate hepatic impairment.Children; Not recommended. Contra-Indications: Pregnancy.Hypersensitivity to donepezil, piperidine derivatives or anyexcipients used in ARICEPT. Lactation: Excretion into breastunknown. Women on donepezil should not breast feed. Warning andPrecautions: Initiation and supervision by a physician withexperience of Alzheimer's dementia. A caregiver should beavailable to monitor compliance. Regular monitoring to ensurecontinued therapeutic benefit, consider discontinuation whenevidence of a therapeutic effect ceases. Exaggeration ofsuccinylcholine-type muscle relaxation. Avoid concurrent use ofanticholinesterases, cholinergic agonist, cholinergicantagonists. Possibility of vagotonic effect on the heart whichmay be particularly important with "sick sinus syndrome," andsupraventricular conduction conditions. Careful monitoring ofpatients at risk of ulcer disease including those receivingNSAIDs. Cholinomimetics may cause bladder outflow obstruction.Seizures occur in Alzheimer's disease and cholinomimetics havethe potential to cause seizures. Care in patients sufferingasthma and obstructive pulmonary disease. As with all Alzheimer'spatients, routine evaluation of ability to drive/operatemachinery. Drug Interactions: Experience of use with concomitantmedications is limited, consider possibility of as yet unknowninteractions. Interactions possible with inhibitors or inducersof Cytochrome P450; use such combinations with care. Possiblesynergistic activity with succinylcholine-type muscle relaxants,beta blockers, cholinergic or anticholinergic agents. Sideeffects: Most commonly diarrhoea, muscle cramps, fatigue, nausea,vomiting, and insomnia. Other common effects in clinical trials(greater than or equal to 5%, and greater than or equal toplacebo) headache, pain, accident, common cold, abdominaldisturbance and dizziness. Rare cases of syncope, bradycardia,heart block and seizures. Rare reports of liver dysfunctionincluding hepatitis. Psychiatric disturbances, includinghallucinations, agitation and aggressive behaviour have beenreported; these resolved on dose reduction or discontinuation.There have been some reports of anorexia, gastric and duodenalulcers and gastrointestinal haemorrhage. Minor increases inmuscle creatine kinase. Presentation and basic NHS costs: Blisterpacked in strips of 14. ARICEPT 5mg; white, film coated tabletsmarked 5 and Aricept, packs of 28 68.32 pounds sterling. ARICEPT10mg; yellow, film coated tablets marked 10 and Aricept, packs 2895.76 pounds. Marketing authorisation numbers: ARICEPT 5mg; PL1055/0006. ARICEPT 10mg; PL 10555/0007. Marketing authorisationholder: Eisai Ltd. Further information from/Marketed by: EisaiLtd, Hammersmith International Centre, 3 Shortlands, London, W68EE and Pfizer Ltd, Sandwich, Kent, CT13 9NJ. Legal Category: POMDate of preparation: May 1999 ots Original Text Service: PfizerInc; Eisai Co., Ltd. Internet: http://www.newsaktuell.de Contact:Celeste Torello of Pfizer, 212-733-6471; or Diane DiBello ofPorter Novelli, 212-601-8235, for Pfizer

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