- Email: [email protected]
P1-386 Pharmacoeconomic benefits of donepezil treatment in severe Alzheimer's disease
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Poster Session PI : Therapeutics and Therapeutic Strategies- Therapeutic Strategies, Behavioral Symptoms POTENT NEUROPROTECTANT PAN-811 T A R G E T S OXIDATIVE STRESS IN O L F A C T O R Y NEUROBLASTS (ONS) DERIVED F R O M
ALZHEIMER'S DISEASE PATIENTS Weiying Pan*, Chantee Dancik, Valery Nelson, Bijan Almassian, Hossein A. Ghanbari. Panacea Pharmaceuticals, Inc., Gaithersburg, MD, USA.
Contact e-mail: [email protected] Background: Alzheimer's disease (AD) is an age-dependent neurodegenerative disease that caused by failure of neuronal function. Recent evidence has demonstrated that increased oxidative stress is a prominent and early feature of vulnerable neurons in AD. Anti-oxidative stress therapy represents a promising approach to prevent or slow the progression of AD. A major limitation in the discovery of new and effective anti-oxidative stress drugs for AD is that the vulnerable neurons of the brain in AD patients can not be studied in a manipulatable system. Olfactory neurons (ONs) are the only neurons of the mammalian CNS that are able to regenerate throughout adult life. Olfactory neuroblasts (ONs), which can replicate in cell culture, exhibit many of in sita characteristics of olfactory neurons, such as the expression of neuron-specific enolase, olfactory marker protein, neurofilaments, and growth-associated protein 43. Moreover, the ONs derived from AD patients exhibit abnormal amyloid precursor protein (APP) processing and increased oxidative damage similar to those found in AD brain. Therefore, cultured ONs are a promising in vitro cellular model for identifying potent drug candidates against oxidative stress in AD. Objective(s): Here we employed this ON model to evaluate PAN-811, a potent neuroprotectant discovered in our laboratory, for AD therapy. Methods: Cultured ONs derived from AD-affected individuals and aged-matched normal controls were pre-treated with varying concentrations of PAN-811 or a vehicle, and then subjected to H202-induced oxidative stress. The cellular expression levels of the oxidative stress markers were evaluated by Immunocytochemical analysis. The ability of PAN-811 to reduce reactive oxygen species (ROS) generation in ONs derived from AD patients was assessed by DCF assay. Results: PAN-811 is capable of reducing oxidative stress in ONs derived from AD patients as well as age-matched normal controls and enhancing the ability of ONs derived from AD patients against H202-induced oxidative stress with art efficacy does of 10 txM. Moreover, PAN-811 attenuates ROS generation in ONs derived from AD patients in a does-dependent manner. Conclusions: These data suggest that PAN-811 represents a new and potential drug candidate to target oxidative stress for use in AD therapy.
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A HEAD TO HEAD STUDY OF DONEPEZIL, R I V A S T I G M I N E , AND GALANTAMINE F O R T H E TREATMENT OF ALZHEIMER'S DISEASE: SAFETY, TOLERABILITY, CLINICAL AND CAREGIVER
IMPRESSIONS AFTER 9 MONTHS OF TREATMENT Joshua R. Shua-Haim* 1, Mark D. Pass 1, Snhas Pate11, Sameer Patel 1 Paul Lee 1, Pritesh Patel 1, Juanita Smith 2. 1jersey Shore University
Medical Center, Neptune, NJ, USA; 2Ocean Medical Center, Brick, NJ, USA. Contact e-mail: markpass @hotmaiLcom Background: Mid-Atlantic Geriatric Fellowship Program, Department of Geriatrics, Jersey Shore University Medical Center & Ocean Medical Center, NJ Objective: To compare safety, tolerability, and efficacy of donepezil, rivastigmine, and galantamine for the treatment of Alzheimer's disease in naive patients. Methods: All patients in our clinical practice who were treated for 6 months with donepezil, rivastigmine, and galantamine were evaluated during a one month period. Patients previously treated with any of these medications were excluded. All met the DSM-IV and NINCDSADRA criteria for possible Alzheimer's disease. Donepezil was initiated at 5 rag/day at 12 P.M. and titrated to 10 rag/day after 1-2 months. Rivastigmine was initiated at 3 mg/day in 2 divided doses. After one month, the dose was increased again to 6 mg/day in 2 divided doses. The same pattern of titration was used until 12 rag/day was achieved. Galantamine was initiated at 8 rag/day in 2 divided doses, and then was increased by 8 rag/month until a maximum of 24 mg/day was reached. Evaluation at monthly intervals included questioning for adverse events and the MMSE. Results:
28 patients were evaluated after 9 months of treatment (8 on donepezil, 11 on rivastigmine, and 9 on galantamine). Average age was 83, 82, and 81 respectively. Average initial MMSE were 16, 14, and 16 respectively. One patient had increased irritability when donepezil was increased to 10 rag/day, but the symptoms resolved after the dose was reduced to 5 mg/day. Weight loss was reported in one patient treated with rivastigmine, and two patients experienced increased somnolence (all were receiving 12 mg/day when adverse events reported). One patient treated with galantamine experienced an adverse event, reported nausea at 16 mg/day which resolved by decreasing the dose to 12 nag/day. Average MMSE decreased by 1.4 in the donepezil group, increased by 1.0 in the galantamine group, and increased by 1.2 in the rivastigmine group. The overall average increase in MMSE was 1.1. In all groups, caregivers denied any noticeable memory improvement. Conclusion: During a 9 month head to head comparison, there were no significant differences in safety or efficacy between these three medications.
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PHARMACOECONOMIC BENEFITS OF
DONEPEZIL TREATMENT IN SEVERE ALZHEIMER'S DISEASE S.N. Shah* 1, H. Feldman 2, S. Gauthier 3 , J. Hecker 4, B. Vellas 5, M. Hux 6, Y. Xn 1, E. Schwam I , M. Leaderer 1. 1Pfizerlnc, New York, NY USA;
2Division of Neurology, UBC Hospital, Vancouver, BC, Canada; 3McGill Center for Studies in Aging, Verdun, PQ, Canada; 4Repatriation General Hospital, Daw Park, Australia; 5Toulouse University Alzheimer's Center, Toulouse, France; 61nnovus Research Inc, Burlington, ON, Canada. Contact e-mail: [email protected] Background: Modeled economic data suggests that there may be a beneficial economic impact of treatment with acetylcholinesterase inhibitors (AChEIs) that extends into the severe stage of Alzheimer's disease (AD). However, no actual randomized clinical trial (RCT) data has yet directly evaluated the economic benefits of donepezil for patients with severe AD. Objective: A cost-consequence analysis was conducted to evaluate the impact of donepezil treatment versus placebo on AD-related costs to society in a subgroup of patients with severe AD (sMMSE 5-12) from a doubleblind RCT of moderate to severe AD (sMMSE 5-17). Methods: Patient and caregiver health resource use were collected prospectively using the Canadian Utilization of Services Tracking (CAUST) questionnaire. Data on caregiver time was collected using the modified Instrumental Activities of Daily Living Scale (IADL+) and Physical Self-Maintenance Scale (PSMS+). The costs for 24 weeks of treatment were calculated for patients in each treatment group based on the frequency of resource use multiplied by unit prices for each resource. Caregiver time was valued at the average minimum wage for Ontario, at Can $6.85 (US $4.62). Total cost to society, adjusted for each patient's AD-related cost over the 3-month period prior to baseline, was compared between treatment groups. Results: 145 patients with severe AD (sMMSE 5-12) were randomized to receive donepezil (n = 72) or placebo (n = 73). After 24 weeks, the total adjusted costs were more for the placebo group (Can $11,968; US $8078) versus the donepezil group (Can $11,501; US $7763). The mean caregiver time spent in patient care was higher for the placebo group compared with donepezil (1034 vs 871 hours). Conclusions: The cost of medication is offset and additional savings are observed with donepezil treatment, mainly due to saved caregiver time. Thus, not treating patients incurs almost equivalent overall costs compared with treating patients with donepezil. Patient and caregiver benefits are greater with treatment.
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Poster Session PI : Therapeutics and Therapeutic Strategies- Therapeutic Strategies, Behavioral Symptoms POTENT NEUROPROTECTANT PAN-811 T A R G E T S OXIDATIVE STRESS IN O L F A C T O R Y NEUROBLASTS (ONS) DERIVED F R O M
ALZHEIMER'S DISEASE PATIENTS Weiying Pan*, Chantee Dancik, Valery Nelson, Bijan Almassian, Hossein A. Ghanbari. Panacea Pharmaceuticals, Inc., Gaithersburg, MD, USA.
Contact e-mail: [email protected] Background: Alzheimer's disease (AD) is an age-dependent neurodegenerative disease that caused by failure of neuronal function. Recent evidence has demonstrated that increased oxidative stress is a prominent and early feature of vulnerable neurons in AD. Anti-oxidative stress therapy represents a promising approach to prevent or slow the progression of AD. A major limitation in the discovery of new and effective anti-oxidative stress drugs for AD is that the vulnerable neurons of the brain in AD patients can not be studied in a manipulatable system. Olfactory neurons (ONs) are the only neurons of the mammalian CNS that are able to regenerate throughout adult life. Olfactory neuroblasts (ONs), which can replicate in cell culture, exhibit many of in sita characteristics of olfactory neurons, such as the expression of neuron-specific enolase, olfactory marker protein, neurofilaments, and growth-associated protein 43. Moreover, the ONs derived from AD patients exhibit abnormal amyloid precursor protein (APP) processing and increased oxidative damage similar to those found in AD brain. Therefore, cultured ONs are a promising in vitro cellular model for identifying potent drug candidates against oxidative stress in AD. Objective(s): Here we employed this ON model to evaluate PAN-811, a potent neuroprotectant discovered in our laboratory, for AD therapy. Methods: Cultured ONs derived from AD-affected individuals and aged-matched normal controls were pre-treated with varying concentrations of PAN-811 or a vehicle, and then subjected to H202-induced oxidative stress. The cellular expression levels of the oxidative stress markers were evaluated by Immunocytochemical analysis. The ability of PAN-811 to reduce reactive oxygen species (ROS) generation in ONs derived from AD patients was assessed by DCF assay. Results: PAN-811 is capable of reducing oxidative stress in ONs derived from AD patients as well as age-matched normal controls and enhancing the ability of ONs derived from AD patients against H202-induced oxidative stress with art efficacy does of 10 txM. Moreover, PAN-811 attenuates ROS generation in ONs derived from AD patients in a does-dependent manner. Conclusions: These data suggest that PAN-811 represents a new and potential drug candidate to target oxidative stress for use in AD therapy.
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A HEAD TO HEAD STUDY OF DONEPEZIL, R I V A S T I G M I N E , AND GALANTAMINE F O R T H E TREATMENT OF ALZHEIMER'S DISEASE: SAFETY, TOLERABILITY, CLINICAL AND CAREGIVER
IMPRESSIONS AFTER 9 MONTHS OF TREATMENT Joshua R. Shua-Haim* 1, Mark D. Pass 1, Snhas Pate11, Sameer Patel 1 Paul Lee 1, Pritesh Patel 1, Juanita Smith 2. 1jersey Shore University
Medical Center, Neptune, NJ, USA; 2Ocean Medical Center, Brick, NJ, USA. Contact e-mail: markpass @hotmaiLcom Background: Mid-Atlantic Geriatric Fellowship Program, Department of Geriatrics, Jersey Shore University Medical Center & Ocean Medical Center, NJ Objective: To compare safety, tolerability, and efficacy of donepezil, rivastigmine, and galantamine for the treatment of Alzheimer's disease in naive patients. Methods: All patients in our clinical practice who were treated for 6 months with donepezil, rivastigmine, and galantamine were evaluated during a one month period. Patients previously treated with any of these medications were excluded. All met the DSM-IV and NINCDSADRA criteria for possible Alzheimer's disease. Donepezil was initiated at 5 rag/day at 12 P.M. and titrated to 10 rag/day after 1-2 months. Rivastigmine was initiated at 3 mg/day in 2 divided doses. After one month, the dose was increased again to 6 mg/day in 2 divided doses. The same pattern of titration was used until 12 rag/day was achieved. Galantamine was initiated at 8 rag/day in 2 divided doses, and then was increased by 8 rag/month until a maximum of 24 mg/day was reached. Evaluation at monthly intervals included questioning for adverse events and the MMSE. Results:
28 patients were evaluated after 9 months of treatment (8 on donepezil, 11 on rivastigmine, and 9 on galantamine). Average age was 83, 82, and 81 respectively. Average initial MMSE were 16, 14, and 16 respectively. One patient had increased irritability when donepezil was increased to 10 rag/day, but the symptoms resolved after the dose was reduced to 5 mg/day. Weight loss was reported in one patient treated with rivastigmine, and two patients experienced increased somnolence (all were receiving 12 mg/day when adverse events reported). One patient treated with galantamine experienced an adverse event, reported nausea at 16 mg/day which resolved by decreasing the dose to 12 nag/day. Average MMSE decreased by 1.4 in the donepezil group, increased by 1.0 in the galantamine group, and increased by 1.2 in the rivastigmine group. The overall average increase in MMSE was 1.1. In all groups, caregivers denied any noticeable memory improvement. Conclusion: During a 9 month head to head comparison, there were no significant differences in safety or efficacy between these three medications.
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PHARMACOECONOMIC BENEFITS OF
DONEPEZIL TREATMENT IN SEVERE ALZHEIMER'S DISEASE S.N. Shah* 1, H. Feldman 2, S. Gauthier 3 , J. Hecker 4, B. Vellas 5, M. Hux 6, Y. Xn 1, E. Schwam I , M. Leaderer 1. 1Pfizerlnc, New York, NY USA;
2Division of Neurology, UBC Hospital, Vancouver, BC, Canada; 3McGill Center for Studies in Aging, Verdun, PQ, Canada; 4Repatriation General Hospital, Daw Park, Australia; 5Toulouse University Alzheimer's Center, Toulouse, France; 61nnovus Research Inc, Burlington, ON, Canada. Contact e-mail: [email protected] Background: Modeled economic data suggests that there may be a beneficial economic impact of treatment with acetylcholinesterase inhibitors (AChEIs) that extends into the severe stage of Alzheimer's disease (AD). However, no actual randomized clinical trial (RCT) data has yet directly evaluated the economic benefits of donepezil for patients with severe AD. Objective: A cost-consequence analysis was conducted to evaluate the impact of donepezil treatment versus placebo on AD-related costs to society in a subgroup of patients with severe AD (sMMSE 5-12) from a doubleblind RCT of moderate to severe AD (sMMSE 5-17). Methods: Patient and caregiver health resource use were collected prospectively using the Canadian Utilization of Services Tracking (CAUST) questionnaire. Data on caregiver time was collected using the modified Instrumental Activities of Daily Living Scale (IADL+) and Physical Self-Maintenance Scale (PSMS+). The costs for 24 weeks of treatment were calculated for patients in each treatment group based on the frequency of resource use multiplied by unit prices for each resource. Caregiver time was valued at the average minimum wage for Ontario, at Can $6.85 (US $4.62). Total cost to society, adjusted for each patient's AD-related cost over the 3-month period prior to baseline, was compared between treatment groups. Results: 145 patients with severe AD (sMMSE 5-12) were randomized to receive donepezil (n = 72) or placebo (n = 73). After 24 weeks, the total adjusted costs were more for the placebo group (Can $11,968; US $8078) versus the donepezil group (Can $11,501; US $7763). The mean caregiver time spent in patient care was higher for the placebo group compared with donepezil (1034 vs 871 hours). Conclusions: The cost of medication is offset and additional savings are observed with donepezil treatment, mainly due to saved caregiver time. Thus, not treating patients incurs almost equivalent overall costs compared with treating patients with donepezil. Patient and caregiver benefits are greater with treatment.