Press release:
New data presented at the International Conference on Alzheimer’s Disease (ICAD): Effectiveness and beneficial effects of AXURA® / AKATINOL® (Memantine)
Honolulu, Hawaii – [July 15, 2010]
Has the role of non-pharmacological treatment (NPT) in the management of Alzheimer’s disease (AD) been over-estimated? Study results discussed at the International Conference on Alzheimer’s Disease (ICAD) suggest that patients with AD did not benefit from additional NPT e.g. occupational / physiotherapy and cognitive training compared to patients receiving Memantine monotherapy. The data of two recent non-interventional studies support that AXURA® / AKATINOL® – an uncompetitive NMDA receptor antagonist – is effective in the treatment of moderate to severe AD and provides beneficial effects on caregiver time. Another positive aspect for Memantine is related to rising health care costs discussion.
Alzheimer’s disease (AD) leads to increased cognitive, communicative and functional deficits and behavioral disturbances. Therefore the patients’ needs are complex. The decline associated with the progressive disease also places a considerable burden on caregivers and the health system. For the treatment of AD regimens including pharmacological and non-pharmacological therapies (NPT) are used. Due to International Treatment Guidelines for Alzheimer’s disease the management of AD should focus on an evidence-based antidementia treatment strategy. Placebo-controlled, double-blind, randomized clinical trials, metaanalyses (1) and responder analyses (2) show the efficacy and tolerability of Memantine in moderate to severe AD. But reliable conclusions for the potential benefits of NPT are difficult to draw.
The efficacy and costs of Memantine and concomitant NPT in patients with moderate to severe AD in everyday clinical practice were investigated in an observational study in Germany. (3) The results of this one year outcome research study including 872 outpatients with moderate to severe AD show that non-pharmacological therapies provided no statistically significant benefit in combination with Memantine treatment compared to standard Memantine monotherapy. On the other hand average costs exceeded those of patients with monotherapy by 49% (annual average costs amount 5.066 Euro per patient vs. 3.410 Euro). In this study two cohorts of patients were observed (mean age 77 years, 59% female). Cohort “pure” includes 401 patients receiving Memantine treatment alone. Cohort “plus” compassed 471 patients treated with Memantine and NPT. Assessments during the observational period were at the beginning, after 3 and 12 months Barthel Index, Nurses Observation Scale for Geriatric Patients (NOSGER), Minimental State Examination (MMSE), Clinical Global Impression of Change (CGI-C) and quarterly, cost related parameters. Patients were treated for one year with Memantine (Axura®); median dose of Memantine was 20 mg Memantine / day. The most frequently initial NPTs were occupa-tional/physiotherapy (54%) and cognitive training (23%). There were a total of 70 different therapeutic regimens. At the end of the one year observational period additional clinical benefits of NPTs were low and the outcome results were not significantly superior to memantine monotherapy. AXURA® / AKATINOL® has once again been proven as a safe and tolerable treatment option in Alzheimer’s patients in a “real world” setting.
In another non-interventional study of Memantine in nursing home residents with AD Memantine has proven beneficial effects on caregivers time: Caregiver time was reduced or stabilized for 94% of patients during the 24 week observational period. (4) At the end of 24 weeks, mean daily caregiver time was reduced by 12.14 (+ 37) minutes. 27.8% of caregivers could save up to 2 hours / day. Data from 1.325 patients (70% female, mean age 79 years) with moderate to severe AD were analyzed in the total safety set. Data for caregiver time was documented for 1.124 patients. Median caregiver time spent at the beginning was 148 minutes. 91% of caregivers spent up to 4 hours / day for the patient’s care. Patients were treated for 24 weeks with Memantine (Axura®), mean dose of Memantine was 18.33 (+ 5) mg / day. Patient’s abilities were assessed at the beginning of the study, and at weeks 4, 8, 12 and 24 using MMSE, the Functional Assessment Scale (FAST), NOSGER and CGI-C. Furthermore, relevant parameters for the care of patients were assessed: at the beginning, the nursing care level and the time spent for patients care by caregivers. The change of caregiver time was documented during the observational period. The majority of patients in the group “caregiver time saved” showed improvement in MMSE total score and improvement or stabilization of their functional abilities measured as change of FAST stage. These findings were in accordance with physicians’ clinical evaluations. Patients with reduced or stabilized caregiver time showed a statistically significant reduction of NOSGER total score over 24 weeks treatment with Memantine. The change of CGI-C was judged as improved in 79.2% of patients and stabilized in 14.2% of patients.
The Alzheimer’s Society is concerned that antipsychotic drugs are being over-prescribed to people with dementia. (5) About 90% of patients with AD experience hallucinations, paranoia, agitation and aggressive behavior. Although associated with serious adverse events, antipsychotics are frequently prescribed as first-line pharmacological treatment for neuropsychiatric symptoms. A study group investigated the use of antidementia drugs (ADDs) and of antipsychotics (APs) in patients with incident AD in the UK. The findings of this analysis: At initiation of AD treatment, a larger proportion of patients treated with Memantine compared with acetylcholinesterase inhibitors (AChEIs) are on AP-therapy. This possibly reflects the different registered indications, and/or that physicians preferentially use Memantine in AP treated patients due to its well-known treatment effects on behavioral disturbances in AD patients
Data source of this analysis was the primary care UK General Practice Research Database (GPRD). The cohort included patients 60 to 90 years with at least 182 days eligibility in GPRD, and with newly diagnosed AD. AD was defined by the earliest entry of an AD recording and prescription of an antidementia drug, either AChEI or Memantine. The incident AD cohort comprised 8.510 patients with 3.664 (43.1%) completing at least 24 months of observation. The proportion of females was 66.9%, predominantly in age 80 to 89. While 4.693 (55.1%) remained untreated during the entire observational period, 3.817 (44.9%) in the AD cohort were given AChEI and / or Memantine. Of those treated, 3.698 patients (96.9%) were initially given AChEI, 115 (3.0%) Memantine and 4 (0.1%) AChEI and Memantine. The median duration from incident AD to the first AChEI and Memantine prescription was 1.9 and 7.6 months respectively. In the AD cohort, 12.5% (1.065/8.510) of patients were given APs in the 182 days prior to AD and 30.1% during the observational period. At initiation of AChEI treatment 10.7% of patients had used APs in contrast to 18.3% at initiation of Memantine treatment. AP use among switchers from AChEI to Memantine was 23.7%.
Dementia is a progressive, degenerative brain syndrome that affects memory, thinking, behavior and emotion. Dementia knows no social, economic, ethnic or geographical boundaries and affects people throughout the world. When dementia progresses affected individuals need care with all aspects of daily life, world-wide mostly families provide this care. Alzheimer’s disease is the most common cause of dementia and accounts for 50-60% of all cases and is caused by abnormal brain tissue changes. International studies make it clear that dementia occurs in every country of the world. Dementia affects 1 in 20 people aged 65 plus and 1 in 5 aged 80 plus. Worldwide there are an estimated 30 million people with dementia. By 2050 the number will rise to over 100 million. (6) Alzheimer’s disease affects 5.3 million people in the U.S. and is the 7th leading cause of death. AD causes 172 billion dollars in annual costs and puts a heavy burden on 10.9 million unpaid caregivers. (7) In light of this, drugs like AXURA® / AKATINOL® may represent an impactful treatment choice to efficiently face this socioeconomic challenge.
References
1 Winblad et al., Dement Geriatr Cogn Disord 2007, 24: 20-27
2 Wilkinson & Andersen, Dement Geriatr Cogn Disord 2007, 24: 138-145
3 Sallach et al., Effectiveness of memantine and non-pharmacological concomitant therapies in patients with moderate Alzheimer’s disease. Poster presented at the 10th Alzheimer’s Association International Conference on Alzheimer’s Disease (Alzheimer’s Association ICAD), July 2010, Hawaii
4 Riepe et al., Beneficial effects of memantine on caregivers time – results of an observational study in moderate to severe Alzheimer´s disease. Poster presented at the 10th Alzheimer’s Association International Conference on Alzheimer’s Disease (Alzheimer’s Association ICAD), July 2010, Hawaii
5 Alzheimer’s Society, www.alzheimers.org.uk
6 Rietbrock et al., Alzheimer’s disease and use of antipsychotics in the UK. Poster presented at the 10th Alzheimer’s Association International Conference on Alzheimer’s Disease (Alzheimer’s Association ICAD), July 2010, Hawaii
7 Alzheimer’s Disease International (ADI), www.alz.co.uk
About Memantine
Memantine is an NMDA-receptor antagonist, the first in a class of AD medications with a unique mechanism of action that focuses on the glutamatergic system. Glutamate is the most common excitatory neurotransmitter in the CNS and the modulation of the glutamatergic neurotransmission is a major target for the treatment of Alzheimer’s disease.
Memantine was developed by Merz and licensed to Forest for the U.S. and Lundbeck for selected European and international markets. Memantine is marketed under the brands Axura® and Akatinol® by Merz, Namenda® by Forest and Ebixa® by Lundbeck.
Merz Pharmaceuticals GmbH (www.merz.com):
Merz Pharmaceuticals, as a member of the Merz Group companies, is an innovative and international healthcare company specializing in the research, development and marketing of pharmaceuticals for the treatment of neurological and psychiatric diseases. Merz is a leader in the field of Alzheimer research and developed memantine as the first drug for the treatment of moderate to severe Alzheimer’s disease. Other franchises covered by Merz are hepatology / metabolic diseases and dermatology.
Contact:
Dr. Jasmine Fokkens
Merz Pharmaceuticals GmbH
Tel.: +49 (0)69 / 15 03 – 804
Fax: +49 (0)69 / 15 03 – 722
E-mail: jasmine.fokkens@merz.de
Overall it sounds like a pretty thorough study by the GPRD.