U.S. Scientific Update
Aricept 23 mg Tablets
Dr. Lynn Kramer
President
NeuroScience Product Creation Unit
Eisai Inc.

Unmet Need in Moderate to Severe
Alzheimer’s Disease (AD)• Ongoing clinical deterioration associated with further
loss of cholinergic neurons• Current treatment options include acetylcholinesterase
inhibitors + memantine• Will moderate to severe Alzheimer’s Disease patients
benefit from higher doses of acetylcholinesterase
inhibitors?
• First study to evaluate efficacy and safety of higher-dose
donepezil (23 mg/day vs 10 mg/day) in this patient group22

Effectiveness and Tolerability of High-Dose(23 mg/day) Versus Standard-Dose (10mg/day) Donepezil in Moderate to Severe
Alzheimer’s Disease: A 24-Week,Randomized, Double-Blind Study
Farlow MR, Salloway SP, Tariot PN, Yardley J, Moline M, Wang Q,
Zou H, Brand-Schieber E, Hsu T, Satlin A

3

Summary View
High-Dose Hypothesis Proven• Study 326 basis of U.S. Food and Drug
Administration approval of Aricept 23 mg tablets• Aricept 23 mg/day demonstrated additional benefit
over 10 mg tablet in patients with moderate-to-severe
Alzheimer’s Disease– Robust cognitive results as measured by theSevere Impairment Battery (SIB)• Addresses unmet medical need– Aricept 23 mg tablets may provide benefit tomoderate-to-severe Alzheimer’s Disease patients• Aricept may not be for everyone. Please see the fullImportant Safety Information and Prescribing
Information at the end of this presentation.
4

Study Overview••5Design• 24-week, double-blind comparison of donepezil 23 mg/day
with donepezil 10 mg/day• Study powered for superiority• Randomization 23 mg/day:10 mg/day, 2:1• Co-primary endpoints: Severe Impairment Battery (SIB),
Clinician’s Interview-Based Impression of Change Plus
Caregiver Input (CIBIC+)• SafetyPopulation• Moderate-to-severe AD (Mini-Mental State Examination(MMSE 0-20)• On Aricept 10 mg IR for a minimum of 3 months before
Screening• Patients taking memantine for at least 3 months before
Screening could be enrolled• N=1467
5

Patient Disposition
Screened(N = 2186)

Randomized(N = 1467)

Safety population(n = 1434)

Donepezil 23 mg/d

Donepezil 10 mg/d(n = 963)(n = 471)

CompletedWithdrawn

CompletedWithdrawn(n = 685)(n = 278)(n = 399)(n = 72)

Reasons for discontinuation•AE (18.8%)•Lack of efficacy (0.1%)•All other (9.9%)
6

Reasons for discontinuation•AE (8.1%)•Lack of efficacy (0%)•All other (7.1%)
6

Demographics Similar Between Groups
Donepezil
23 mg/day

Donepezil
10 mg/day

Safety population

963

471

Mean age (SD)73.9 (8.5)

73.8 (8.6)

Females (%)

63.0

62.4

3.5
91.1
3.6

6.4
87.1
5.3

1.8

1.2

Duration (weeks) of donepezil 10 mg/day
use prior to study, mean (SD)112 (108)105 (99)

Concomitant memantine at baseline (%)

36.6

35.7

Type of residence (%)
Lives alone
Lives with caregiver, relative, or friend
Senior residence, retirement home,assisted living facility
Other

77

SIB: Change from Baseline(ITT Population)
P=0.0001

8

CIBIC+: Overall Change Score
at Week 24 (ITT Population)

The mean difference between the 23 mg/day and 10 mg/day treatmentgroups was 0.06 units. This difference was not statistically significant.
9

Most Frequent Adverse Events Leading
to Discontinuation, by Treatment Group
Dose Group23 mg/day
Aricept963

10 mg/dayAricept
471

30Diarrhea

20Nausea

20Dizziness

10

SafetyPopulation
Event/%
Discontinuing
Vomiting

10

Most Common AEs
Occurring in ≥2% of Patients in Donepezil 23 mg/day Group and With
Higher Frequency Than Donepezil 10 mg/day GroupDonepezil 23 mg/dDonepezil 10 mg/d

Safety population

963

471

% of patients with at least 1 AE

74

64

Nausea123

Vomiting

93

Diarrhea

85

Anorexia

52- - - - - -- - - -- - - - ---------------Dizziness

53

Weight decreased

53Headache

43

Insomnia

32

Urinary incontinence

31

Fatigue

21Asthenia

21

Contusion

20

Somnolence

21

Preferred Term (% of subjects)-------------------------

1111

New FDA Approved Labeling
Aricept 23 mg tablets• Dosage and Administration– Mild to Moderate Alzheimer’s Disease – 5 mg or 10 mg
administered once daily– Moderate to Severe Alzheimer’s Disease – 10 mg or 23 mg
administered once daily• A dose of 10 mg once daily can be administeredonce patients have been on a daily dose of 5 mg for4 to 6 weeks.
• A dose of 23 mg once daily can be administeredonce patients have been on a dose of 10 mg once
daily for at least 3 months.

12

FDA Approved Labeling, Dosage and Administration

Potentially Important Pharmacokinetic
Differences• Both tablets administered once daily– Consistent with half-life >70 hours• PK of Aricept 23 mg/day versus Aricept 10 mg/day (population
PK from Study 326)
– Peak plasma concentration is achieved for Aricept 23 mg
tablets in approximately 8 hours, compared with 3 hours forAricept 10 mg tablets.
– Peak plasma concentrations were almost 2-fold higher for
Aricept 23 mg tablets than Aricept 10 mg tablets• The 23 mg tablet should not be crushed or chewed because
this may increase its rate of absorption

13

Summary•

The study showed that patients on 23 mg/day experienced important
clinical benefit on both measures compared to 10mg/day– Increasing the donepezil daily dose to 23 mg/day provided
statistically significant cognitive benefit (SIB) compared tocontinuing 10 mg/day in patients with moderate to severe AD– Donepezil 23 mg/day did not provide statistically significant
incremental benefit compared to 10 mg/day on global function(CIBIC+) in the overall ITT population•In the pivotal study there were no important differences in the type ofadverse events in patients taking donepezil with or without memantine•

The most frequent adverse events for Aricept 23 mg/day were nausea,vomiting, diarrhea and anorexia•

Aricept may not be for everyone. Please see the full Important Safety
Information and Prescribing Information at the end of this presentation.

1414

Important Safety Information
Aricept may not be for everyone. People at risk for stomach ulcers or who
take certain other medicines should tell their doctors because serious
stomach problems, such as bleeding, may get worse.
People at risk for certain heart conditions should tell their doctor before
starting Aricept because they may experience fainting. People with serious
lung conditions and difficulty breathing, bladder problems or seizures shouldtell their doctor before using Aricept. Aricept 23 mg/day is associated withweight loss. Check with the doctor if this is a concern. Inform the doctor if thepatient needs surgery requiring anesthesia while taking ARICEPT.
Some people may have nausea, diarrhea, difficulty sleeping, vomiting ormuscle cramps. Incidence of nausea and vomiting were markedly greater inpatients taking Aricept 23 mg/day versus patients taking Aricept 10 mg/day.
Some people may feel tired or may have loss of appetite. If they persist,please talk to the doctor.
For Full Prescribing and Patient Information, please visit www.aricept.com.
15

Safe Harbor Statement••••16

Materials and information provided during this presentation may contain so-called“forward-looking statements.” These statements are based on current expectations,forecasts and assumptions that are subject to risks and uncertainties which could
cause actual outcomes and results to differ materially from these statements.
Risks and uncertainties include general industry and market conditions, and generaldomestic and international economic conditions such as interest rate and currency
exchange fluctuations. Risks and uncertainties particularly apply with respect toproduct-related forward-looking statements. Product risks and uncertainties include,
but are not limited to, technological advances and patents attained by competitors;
challenges inherent in new product development, including completion of clinical
trials; claims and concerns about product safety and efficacy; obtaining regulatory
approvals; domestic and foreign healthcare reforms; trends toward managed careand healthcare cost containment; and governmental laws and regulations affecting
domestic and foreign operations.
Also, for products that are approved, there are manufacturing and marketing risks
and uncertainties, which include, but are not limited to, inability to build production
capacity to meet demand, unavailability of raw materials, and failure to gain market
acceptance.
The Company disclaims any intention or obligation to update or revise any forwardlooking statements whether as a result of new information, future events orotherwise.

U.S. Commercial Launch Plan
Aricept 23 mg Tablets
Mr. Lonnel Coats
President and CEO
Eisai Inc.

Important Updates – Aricept 23 mg Tablets• FDA approval has occurred for U.S. market• Eisai / Pfizer commercial organizations prepared and ready tolaunch with 1300 medical representatives in U.S.
• Eisai national launch meeting to occur within 9 days post FDAapproval, via national web-cast to 46 sites across U.S.
• Pfizer plans launch within the week for their field force• Product availability in pharmacies within 9 days post FDA approval• Aricept 23 mg tablets launch in U.S. market will provide a new
dosing option to moderate-to-severe AD patients who may benefit
from this new product18

Aricept 23 mg Tablets May Address Unmet
Needs in the Market• Caregivers of moderate-to-severe Alzheimer’s Disease patientsare continually searching for additional therapeutic options•Aricept 23 mg tablets may provide greater cognitive efficacy formoderate-to-severe Alzheimer’s Disease as compared to Aricept
10 mg tablets• Aricept may not be for everyone. Please see the full Important
Safety Information and Prescribing Information at the end of thispresentation

19

Opportunity at Launch• 63% of all AD patients are currently on Aricept 5 mg or 10 mgtablets• Over 75% of Aricept patients are currently on the 10 mg dose
• Approximately 70% of patients on Aricept 10 mg/day aremoderate-to-severe and may gain additional benefit byincreasing to once-daily 23 mg tablets• Target peak U.S. sales: $600M+ by 2012
• Aricept may not be for everyone. Please see the fullImportant Safety Information and Prescribing Information atthe end of this presentation
Data Sources: IMS NPA, IMS Retail Patient Tracker

20

Opportunity for Aricept 23 mg Tablets toCapture Moderate-to-Severe Segment• Focus opportunity in moderate segment - 45% ofall AD patients– in line with indication, largest patient segment

Aricept IR

Mild

Aricept 23
ModerateSevere

memantine HClrivastigmine transdermalsystem

21

Recent Eisai Activities at International Congress
on Alzheimer’s Disease (ICAD)• Eisai had significant presence at ICAD conference (July2010)• For Aricept 23 mg tablets:– Oral presentation of pivotal study, “Effectiveness and Tolerability ofHigh Dose (23mg/d) Versus Standard–Dose (10mg/d) Donepezil in
Moderate-to-Severe Alzheimer’s Disease,” by Dr. Martin Farlow,
Professor & Vice-Chairman of Research in Department of Neurology,
Indiana University– Poster: Safety profile of higher dose
– Poster: Patients with more advanced Alzheimer’s Disease22

Aricept 23 mg Tablet Managed Care Contract
Strategy• Opportunity:– Focus on key accounts in both Medicare Part D and CommercialBusiness that make up ~ 90% of Aricept 23 mg tablet opportunity• Objective:– Secure and/or protect Aricept 23 mg tablet Tier 2 formulary
positioning• Strategy:– Leverage existing Aricept contracts to maintain Aricept 23 mgtablet formulary access• Pricing:– Maintain parity pricing to the current 5 mg and10 mg tablet

23

Summary•

New market opportunity created for patients who would have to choose notherapy or expensive combination therapy•

Study results showed that patients on 23 mg/day experienced important clinicalbenefit on both measures compared to 10 mg/day– Severe Impairment Battery (SIB) - p=0.0001 (statistically significant)– Clinician’s Interview-Based Impression of Change Plus Caregiver Input(CIBIC+) – p=0.1789 (not statistically significant)•Excellent managed care strategy in place to provide optimal access for patients•

Eisai and Pfizer are excited and aligned to launch Aricept 23 mg tablets within
U.S. market 9 days post FDA approval with 1300 MRS•

Parity pricing to encourage patients to start and stay with Aricept as their diseaseprogresses•

Aricept may not be for everyone. Please see the full Important Safety Information
and Prescribing Information at the end of this presentation

24

Important Safety Information
Aricept may not be for everyone. People at risk for stomach ulcers or who
take certain other medicines should tell their doctors because serious
stomach problems, such as bleeding, may get worse.
People at risk for certain heart conditions should tell their doctor before
starting Aricept because they may experience fainting. People with serious
lung conditions and difficulty breathing, bladder problems or seizures shouldtell their doctor before using Aricept. Aricept 23 mg/day is associated withweight loss. Check with the doctor if this is a concern. Inform the doctor if
the patient needs surgery requiring anesthesia while taking ARICEPT.
Some people may have nausea, diarrhea, difficulty sleeping, vomiting or
muscle cramps. Incidence of nausea and vomiting were markedly greater inpatients taking Aricept 23 mg/day versus patients taking Aricept 10 mg/day.
Some people may feel tired or may have loss of appetite. If they persist,please talk to the doctor.
For Full Prescribing and Patient Information, please visit www.aricept.com.
25

Safe Harbor Statement••••26

Materials and information provided during this presentation may contain so-called“forward-looking statements.” These statements are based on current expectations,forecasts and assumptions that are subject to risks and uncertainties which could
cause actual outcomes and results to differ materially from these statements.
Risks and uncertainties include general industry and market conditions, and generaldomestic and international economic conditions such as interest rate and currency
exchange fluctuations. Risks and uncertainties particularly apply with respect toproduct-related forward-looking statements. Product risks and uncertainties include,
but are not limited to, technological advances and patents attained by competitors;
challenges inherent in new product development, including completion of clinical
trials; claims and concerns about product safety and efficacy; obtaining regulatory
approvals; domestic and foreign healthcare reforms; trends toward managed careand healthcare cost containment; and governmental laws and regulations affecting
domestic and foreign operations.
Also, for products that are approved, there are manufacturing and marketing risks
and uncertainties, which include, but are not limited to, inability to build production
capacity to meet demand, unavailability of raw materials, and failure to gain market
acceptance.
The Company disclaims any intention or obligation to update or revise any forwardlooking statements whether as a result of new information, future events orotherwise.