The value of
Innovative Medicine
in Japan
APRIL 12, 2013

CONFIDENTIAL AND PROPRIETARYExecutive summary
Japan’s healthcare is one of the best in the world, however risks exist that canundermine this world-class care system▪ World-class healthcare system– Highest life expectancy, and one of the lowest mortality rates– Easy physician access with low healthcare spending compared to other countries▪ However, risks exist that could undermine this system– Rapidly ageing population and the need to care for the elderlies– Widening funding gap due to rising healthcare cost and higher fiscal constraint
Investments in healthcare, particularly in innovative medicine can help mitigate theserisks and create significant social and financial benefits▪ Thanks to favorable government policies, a total of 176 medicines have been introduced in
the past five years. These medicines have substantially improved people’s quality of life
▪ These medicines generated significant financial and economic benefit:– more efficient use of medical resources and save cost– enable workers to be more productive thanks to less absenteeism and disability.
Increase quality lifespan so people work longer▪ Using available Japanese data, a study of five best-in-class drugs demonstrated value of
1,300 – 1,500 bn JPY, representing 16% of the total medical spending in these disease
areas
Japanese government should continue to promote innovation through policies andinvestment in healthcare▪ Benefits all stakeholders – e.g. patients, physicians and government etc.
▪ Japanese government should continue to promote innovation through policies andadditional funding| 1

Executive summary

Investments in healthcare can generate significant value:
Japan has a worldclass healthcare
system:Innovative
medicine canreduce total
medicaltreatment
costs▪ Easy access▪ One of the best
outcomes▪ Spending level
relatively low

There are risks thatcan undermine thehealthcare system

Create jobs
inhealthcare

OVERALLHEALTHIERPOPULATION

Attractmorescientifictalent▪ Ageing population▪ Widening funding
gap
Createpositive
GDP impact| 2

Contents

Japan’s healthcare is the one of the best in the world,
however risks exist that can undermine this system

Investments in healthcare, particularly in innovative
medicine can help mitigate these risks

The importance of innovative medicine has implications
on a number of stakeholders| 3

Japan has one of the healthiest populations in the world –Highest life expectancy and one of the lowest infant mortality rate
RANKED FROM BEST TO WORST
Life expectancy at birthPotential years of life lost1

Years; 2009

Years lost/100,000 population aged 0-69; 2009

Japan
Switzerland
Italy
Spain
Australia
Israel
IcelandSwedenFranceNorwayNew Zealand
CanadaLuxembourg
Netherlands
Austria

83.0
82.3
81.8
81.8
81.6
81.6
81.5
81.4
81.0
81.0
80.8
80.7
80.7
80.6
80.4

IcelandSwedenItaly
Japan
IsraelNetherlands
Spain
NorwayLuxembourg
Germany
CanadaAustria
GreeceKorea
United Kingdom

2,415
2,610
2,666
2,669
2,714
2,812
2,851
2,917
2,953
3,184
3,217
3,263
3,279
3,344
3,378

1 Potential years of life lost (PYLL) is a summary measure of premature mortality which provides an explicit way of weighting deaths occurring at younger ages, whichare, a priori, preventable
SOURCE: OECD| 4

Japan also has the lowest mortality from major disease (e.g., cancer,
circulatory diseases, diabetes)
RESULTS OF INTERNATIONAL COMPARISON OF HEALTH INDICATORS
Mortality rate for seven diseases in Japan

Overall rating
1

Japan

A

2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17

Switzerland
Italy
NorwayFinlandSwedenFranceAustralia
Germany
CanadaNetherlands
Belgium
Austria
UK
IrelandDenmark
US

A
A
B
B
B
B
B
B
B
C
C
C
C
D
D
D

Indicators

Rating1

Mortality Due to Cancer

A

Mortality Due to Circulatory Diseases

A

Mortality Due to Respiratory Diseases

C

Mortality Due to DiabetesA

Mortality Due to Musculoskeletal System Diseases

A

Mortality Due to Mental Disorders

A

Mortality Due to Medical Misadventures

A

1 A country receives a report card rating of “A” on a given indicator if its score is in the top quartile; a “B” if its score is in the second quartile; a “C” if its score is in thethird quartile; and a “D” if its score is in the bottom quartile
SOURCE: Conference Board of Canada based on OECD Health Data 2009| 5

Japanese patients enjoy the best physician access and care quality
Good accessGood quality

Moderate cost

Almost all (>80%) patients can get
same/next-day appointment1%; 2012In-hospital case-fatality rates within
30 days after admission forischemic stroke, %; 2009

Health-care cost per capita2$ thousand PPP; 2009

Japan2

100

France

86

Korea

1.8

Japan

1.8

Denmark

2.6

Switzerland

62

Norway2.8

Netherland

61

Finland

2.8

New Zealand

59

Iceland

2.8

United States

3.0

Germany

56

Austria

3.1

UK

55

Italy

3.4

Israel

3.5

US.

47

Sweden3.9

Norway42

Germany

4.0

Australia

38

Switzerland

4.3

Luxembourg

4.5

Canada22

New Zealand

5.4

Spain
Italy
FranceJapan
FinlandUnited Kingdom
Belgium
Germany
IcelandSwedenDenmark
CanadaAustria
Australia
IrelandNetherlands
Switzerland
United States
NorwayLuxembourg

32
33
34
34
35
36
36
36
37
37
38
38
39
39
40
41
45
46
56
86

1 Percent of physician reporting that Almost all (>80%) of patients can get same/next-day appointment when sick
2 Data on Japan is from expert insights and MHLW data.
3 The data for Japan, Portugal, and Australia for 2008.
SOURCE: OECD Health Data; Commonwealth Fund International Survey; MHLW

| 6

Japan also has the lowest total healthcare spending as a percentage
of GDP, and per capita spending among G7 counties
National healthcare spending as Per-cent of GDP and Per-capita spending1 (2010)
Per-capita healthcare spending

Healthcare expenditure % of GDP

Per capita
USD% of GDP
20

8,000

17.6
10% in 2011

15
11.6

11.6

6,000

11.4
9.6

10

9.3

9.2

4,000

5

2,000

0

0

USA

SOURCE: OECD;MHL;World bank

FRA

GER

CAN

UK

ITA

JPN

| 7

However, emerging demographic and economic risks could
undermine this world-class healthcare system
Risk of lost
productivity as
population
ages

Ageingpopulation

Increasingneed/cost of carefor patientsHEALTHCARESYSTEM
CHALLENGED

Challenged
healthcare
system can▪ Impact
Economic/
GDP loss

population’squality life

▪ Affect social
stability

Funding
gap forhealthcare| 8Ageing population and the need/cost to provide care for the elderlies

Japanese population is ageing rapidly tounprecedented level

Elderly uses healthcare more than average
population, 2008

Population age 65 and over
% of population

Spending
tJPY/person

+132%

40
36
35
31
30
25
20

Japan
Germany

25
France
23
21 UK
US

15

133

261

+186%

Hospitalization
day/person

1
Outpatient
visit
day/person

103

688

1

11

7

Avg.
4

3

+91%

10

Avg.
283

28
Avg.
14

13

0

1990 2000 2010 2020 2030 2040
SOURCE: UN; MHLW

0-14 15-44 45-64

65+
| 9

Widening funding gap for healthcare expenditures

EXPENDITURE ON MEDICAL AND LONG-TERM CARE
JPY trillions1
~107

48

~60
4

55-66

2011

15E

~23

Fundinggap

77-83

Fundingavailable

~77
~9

64-68

20E

2025E

1 Based on 2008 estimate at Prime Minister Office (“社会保障国民会議”)
2 Based on 2011 estimate at Prime Minister Office (“社会保障・税との一体改革集中検討会議”)
SOURCE: MHLW, Cabinet Secretariat| 10

Contents

Japan’s healthcare is the one of the best in the world,
however risks exist that can undermine this system

Investments in healthcare, particularly in innovative
medicine can mitigate these risks

The importance of innovative medicine has implications
on a number of stakeholders| 11Investments in healthcare helps mitigate these risks and maintainJapan’s healthcare standards at high levels
Japan has a worldclass healthcare
system:Investments in healthcare can generate significant value:
Innovative
medicine can1 reduce total
medicaltreatment
costs▪ Easy access▪ One of the best
outcomes▪ Spending level
relatively low

There are risks thatcan undermine thehealthcare system

23Create jobs
inhealthcare

AttractmorescientifictalentOVERALLHEALTHIERPOPULATION▪ Ageing population▪ Widening fundinggap

4

Createpositive
GDP impact| 12

1 Innovative medicine is the most realistic and impactful driver toenhance healthcare outcomes, loosening fiscal constraints

Avoid productivity loss
Reduce the life-time costof treatments▪ Innovative medicine canmore effectively treat or
prevent diseases– Leading to less need for▪ Improve patients’ healthlevel to above productivity
level▪ Thus contribute toadditional GDP growth to
reduce funding gap

care or hospitalization,
particularly for elderlies| 13

Innovative medicine introductions in Japan have been speeding up,
thanks to favorable government policy
New medicine introductions, 2008-12
Molecule count▪ A total of 176
46
38
34

33

medicines havebeen introducedin the past fiveyears

▪ Average new
medicine review
time has been
reduced from 22months to 11
months25▪ Simultaneous
global trials havebeen increasing
2008

09

Source: MHLW; PMDA; Asu no Shinyaku

10

11

2012

| 14

We selected five best-in-class medicines where Japanese data are
available and quantified their financial and economic benefits

5 disease areas
Diabetes

TOTAL VALUE OF 5 MEDICINES
JPY billions
800-950

1,300-1,500

500-550

Chronic obstructive
pulmonary disease
Chronic kidneydiseaseStroke prevention
atrial fibrillation
Depression

Total medical
treatment costsavings▪ Allows more
efficient use of
medical resources,
and saves costthrough better
effectiveness andfewer side effects

Economic benefit ofproductivity gains

Total economic
value▪ Enables workers to
be more productive
thanks to lessabsenteeism anddisability. Increases
lifespan so people
work longer| 15

1 The total value net of drug costs of five best-in-class innovative

drugs are between1,300 bn to 1,500 bn JPY
Case study drug

Disease

Sources of value

Included patients▪ Slow down progression of▪ 40-50 years old

disease if treatment is initiatedearly when symptoms are still
mild

COPD

▪ Enhanced reduction in HbA1c
resulting in less incidence ofvarious diabetic complications;no hypoglycemia

Diabetes▪ Compared to warfarin, lower

Strokeprevention
in AF

incidence of stroke, intracranial
hemorrhage and all-cause
mortality▪ Increased in remission ratecompared to placebo resulting
in more patients returning towork and preventing GDP loss

Depression▪ Mean arterial BP reduction andChronic
kidneydisease(CKD)1
Nu Lotan

renal protective effect delay theneed for dialysis and reduceincidence of othercomplications such as renaltransplant

1 For CKD caused by diabetic nephropathy only
SOURCE: Industry research; Japan clinical data; Literature search; Expert interviews

males and females

Value
Billion JPY~70▪ 40-70 years oldmales and females

35~138▪ 40+ years old males
and females

1,050▪ 15-64 years oldmales and females

80~165▪ 50-69 years oldmales only

Additional value of 626 bn
JPY if productive age
increases from 65 to 70~80~1,300-1,500
bn JPY

| 16

COPD

1 Overview of the value of Spiriva compared withplacebo

Applicable population

Value based on the applicable population
JPY billion
70

Patients 40-50 years oldmales and females until death0

Costsavings

Productivity
preservation▪ Slow down pro-▪ Preservation ofgression of
COPD

70

Total
value

productivity inlater years isoffset by loss in
productivity due toneed for receiving
treatment inearlier years

SOURCE: 1 Salmeterol and Fluticasone Propionate and Survival in Chronic Obstructive Pulmonary Disease, February 22,
2007, Peter M.A. Calverley, et al., N Engl J Med| 17

DIABETES (1 of 2)

1 Overview of the value of Januvia comparedwith αGI

Applicable population

Value based on the applicable population
JPY billion
110

Cost
savings
Patients 40-70 years oldmales and females until death▪ Reducing
complications
from diabetes

138

28

Productivity
preservation

Total
value

▪ Maintaining
workforce healthlevel above
productivity level

SOURCE: 1 Relationship between glycated haemoglobin and microvascular complications: Is there a natural cut-off point for the diagnosis of diabetes?, C. Sabanayagam, et al., 2009, Diabetologia
2 Cardiovascular safety of sitagliptin in patients with type 2 diabetes mellitus: a pooled analysis, Engel SS, 2013, Cardiovasc Diabetol
3 Effects of sitagliptin beyond glycemic control: focus on quality of life, Yoshiko Sakamoto, et al., 2013, Cardiovascular Diabetology 2013
4 The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study, 2009, Denise E Bonds, et al., BMJ| 18

DIABETES (2 of 2)

1 Overview of the value of Januvia + SU comparedwith SU

Applicable population

Value based on the applicable population
JPY billion

35

68
-33
Cost
savings
Patients 40-70 years oldmales and females until death▪ Cost of Januvia
as an add-on
therapy, net ofsavings inmedical care

Productivity
preservation

Total
value

▪ Maintaining
workforce healthlevel above
productivity level

SOURCE: 1 Relationship between glycated haemoglobin and microvascular complications: Is there a natural cut-off point for the diagnosis of diabetes?, C. Sabanayagam, et al., 2009, Diabetologia
2 Cardiovascular safety of sitagliptin in patients with type 2 diabetes mellitus: a pooled analysis, Engel SS, 2013, Cardiovasc Diabetol
3 Effects of sitagliptin beyond glycemic control: focus on quality of life, Yoshiko Sakamoto, et al., 2013, Cardiovascular Diabetology 2013
4 The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study, 2009, Denise E Bonds, et al., BMJ| 19

STROKE PREVENTION IN AF

1 Overview of the value of Apixaban compared with

WarfainApplicable population

Value based on the applicable population
JPY billion
730

Cost
savings
Patients 40+ years old males
and females until death▪ More effectively
preventing stroke▪ With fewer

1,050
320

Productivity
preservation

Total
value

▪ Maintaining
workforce healthlevel above
productivity levelcomplications
such as bleeding

SOURCE: 1 Apixaban versus Warfarin in Patients with Atrial Fibrillation, September 15, 2011, Christopher B. Granger, N Engl J Med
2 Cost-Effectiveness of Apixaban Compared with Warfarin for Stroke Prevention in Atrial Fibrillation, Soyon Lee, et al., 2012, PLOS ONE| 20

DEPRESSION

1 Overview of the value of Cymbalta compared withplacebo

Applicable population

Value based on the applicable population
JPY billion

80~165131~216-51
Cost
savings
Patients 15-64 years oldmales and females until death▪ Cost of Cymbalta,
net of savings inmedical care andhospitalization
costs

Productivity
preservation

Total
value

▪ Helping morepatients achieving
remission,bringing themback to work

SOURCE: 1. Enhancing Outcomes from Major Depression: Using Antidepressant Combination Therapies with Multifunctional Pharmacologic
Mechanisms from the Initiation of Treatment, Stephen M. Stahl, 2010, CNS Spectr; 2. Depression Treatment with Duloxetine andReduction of Inability to Work, Michael Happich, et al., 2012, Depression Research and Treatment

| 21

CKD

1 Overview of the value of Nu Lotan compared withplacebo

Applicable population

Value based on the applicable population
JPY billion
80

Patients 50-69 years oldmales only until death0

Costsavings

Productivity
preservation▪ Cost savings in▪ No productivity

drugs, andmedicalexpenses oftreating CKD1
andcomplications
such as dialysis

80

Total
value

preservation as
CKD1 patients
generally pass
the productiveage

1 Caused by diabetic nephropathy
SOURCE: 1 Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy, Barry M. Brenner, et al., September 20, 2001, N Engl J Med
2 Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees
Working Group, Bakris GL, et al., 2000, Am J Kidney Dis| 22

1 Enhance quality of life (1 of 3)
EXAMPLE: COPD

COPD PATIENTWITHINNOVATIVE
DRUGS▪ Suffers from shortness of breathand persistent coughing▪ Loses ability to exercise andcarry out daily activities▪ Spends at least one month1
every year in hospitals

Spends quality
time with
grandchildren
every weekend

Takes a stroll at
the park fivedays a week

1 Based on Japan clinical study of COPD patients
SOURCE: MHLW

| 23

1 Enhance quality of life (2 of 3)
EXAMPLE: DEPRESSION

DEPRESSION PATIENTWITHINNOVATIVE
DRUGS▪ Suffers from low mood and lossof interest in activities▪ Has pain and suicidal thoughts▪ Average period of absence fromwork up to 4.8 months1

Attends closefriends’ birthday
parties andcelebrations oncea monthEnjoys family
dinners withloved ones
every day

1 Based on Japan clinical study of depressive patients
SOURCE: MHLW

| 24

1 Enhance quality of life (3 of 3)
EXAMPLE: DIABETESDIABETES PATIENTWITHINNOVATIVE
DRUGS▪ Suffers from complications suchas blindness and loss limbs▪ A diabetic nephropathy patient
spends on average twomonths1 every year in hospitals

Attends
daughter’s
wedding

Hikes mount Fuji
three times ayear

1 Based on Japan clinical study of diabetic patients
SOURCE: MHLW

| 25

2 Healthcare related jobs were the largest contributor to total job

adds in Japan in 2011

Healthcare related
job adds

INDUSTRIES WITH THE MOST JOBS ADDED 2010-11
Number of jobs createdThousands

Industry

230

Medical, health and welfare
Scientific research, professional & technical60

Education, learning support

60

Real estate and goods rental and leasing

20

Living-related services

20
10

Government, except elsewhere classified
Mining and quarrying of stone and gravel0

Construction

0

Fishery-10

Transport and postal activities-10

Services, except elsewhere classified-10

Finance and insurance-20

SOURCE: Labor force survey by Statistics Bureau of Ministry of Internal Affairs & Communication| 26

3 Having a thriving pharmaceutical industry can attract more scientists

with advanced degrees
2000-10 CAGR
Percent

Number of doctorate in science, 2001-11
18,0003.3

16,000USA1

14,00012,00010,000
8,000
6,000
4,000
2,000

-0.1
Japan202001 02 03 04 05 06 07 08 09 10 2011
1 Number receiving doctorate degrees
2 Number entering doctorate degrees
SOURCE: Country statistics| 27

4 A direct positive impact of innovation on GDP is export – homegrown Japanese medicine has generated sizable exports
Product

Manufacturer Indication2012 sales
JPY billions% Sales outside
Japan

411

94

Antipsychotic

216

38

Hypertension

Gastric andduodenal ulcers

122

37

| 28

Contents

Japan’s healthcare is the one of the best in the world,
however risks exist that can undermine this system

Investments in healthcare, particularly in innovative
medicine can mitigate these risks

The importance of innovative medicine has implications
on a number of stakeholders| 29

Japanese government should continue to promote innovation, which
will create win-win for the overall Japanese society
Government will get fiscal relief which will in turn benefit thehealthcare system
Patients will enjoy better quality of life

Physicians can provide better care solutions for patients

Academia can better attract and develop scientific talentOverall Japan economy will benefit from GDP and job creation| 30

Appendix| 31

Executive summary (1/3)
1 Japan has been successfully delivering superior healthcare

outcomes at moderate cost relative to the OECD peer countries.
However, the emerging demographic and economic risks could
undermine Japan’s achievements▪ Superior healthcare outcome– Japan demonstrates the best performance in health outcomes▫ Highest life expectancy at birth (83.0 years in 2009)▫ One of the lowest infant and premature mortality▫ Lowest mortality from major disease (e.g., cancer, circulatory diseases, diabetes)– Japanese patients enjoy the best physician access and care quality▫ All patients can get same/next-day appoint (e.g., 100% in Japan vs. less than▪

50% in US in 2012)▫ The lowest in-hospital case-fatality rates within 30 days after admission for ischemic stroke (1.8% inJapan vs. 3.0% in US in 2009)
Japan has kept the healthcare spending at a moderate level– The lowest total healthcare spending as a percentage of GDP (i.e., 9.5% of GDP in 2010)– One of the lowest healthcare cost per capita ($34K PPP in Japan vs. $46K PPP in US 2009)▪ Risks that can undermine these achievements:– Growing needs of care for elderlies due to rapidly aging population, e.g., a 65+
year-old patient consumes 132% more spending, 186% more hospitalization
day, and 91% more outpatient visit than an average Japanese– ~90% of corporate health insurance societies (Kempo Kumiai) suffers from deficits
up to JPY 600 billion annual loss in total– The implied productivity growth in healthcare under the government’s growth plan is significantly higher than
the recent slowing trend; thus, more value creation in healthcare is critical to sustain the outcome level– Undermined healthcare outcomes could deteriorate the labor productivity and economic growth| 32

Executive summary (2/3)
2Investments in healthcare, particularly in innovative medicine canprovide a virtuous cycle that help mitigate these risks and create
significant social and financial benefits▪ Investment in innovative medicine can more effectively treat or prevent
diseases, leading to less need for care or hospitalization, particularly forthe elderlies– Innovative medicine can, in fact, 1) reduce the life-time cost of treatments and2) avoid the people’s productivity loss, relieving the funding gap▫ For example, a recent analysis of five innovative drugs in major chronic
diseases suggests these drugs can bring net value of at least JPY 1,300-1,500 billion in total- Selected Diabetes, COPD, CKD, Stroke prevention in AF and Depression that represent 24% of total
medical expenditures in Japan in 2011
- The net value is equivalent to 16 % of total medical expenditures in these five disease areas- Also, the net value is more than twice the funding gap of the Kempo Kumiai▫ Global clinical data where Japan unique data is not available also indicates even higher potential value▫ Similarly, innovative drugs in other major disease areas (e.g., oncology, vaccines) should also bringsignificant value– Moreover, innovative medicine can also enhance patients’ quality of life and create impact that reaches far
beyond financial benifits▫ For instance, a typical 65-year old female COPD patient with severe symptoms who is to largely lose her
ability even to walk and has to stay home everyday for treatment could delay the progression significantly
by an early adoption of innovative drug (e.g. Spiriva) and can spend time with family for outdoor activities▫ Similarly, with innovative medicine, depression patients can achieve remission and enjoy everyday social
life; Diabetes patients can carry on with their daily activities normally and not miss important life events,
such as annual hiking trips to Mount Fuji and children’s wedding| 33

Executive summary (3/3)
2…continued from above▪ Investment in healthcare and innovative medicine will also generate Indirect
but significant impacts for the future growth of Japan– Job creation: Labor productivity enhanced by the innovative medicine
will drive the overall economic growth and job creation, particularly in the growth
sector like healthcare industry– Science talent development: Japan is facing a decline in “science” background PhDs.
Investment in healthcare for driving further innovation will drive the talent development
platform for scientists– Direct R&D investment: As the market environment is further friendly to innovation, Japan will get further
attention from global companies for investment, including more clinical trials throughout Japan and also
more collaborations with Japanese science– Export of Japan-origin innovation: As the major high-tech manufactures used to be, exports of Japanorigin innovation, including new pharmaceutical materials and finished products, can create future economic
gain from overseas (e.g. Blopress from Takeda, and Abilify from Ostuka)

3 Implication to the stakeholders – Investment in healthcare andinnovative medicine will bring all “win-win” to the society▪ Upfront investment in innovative drugs will benefit all stakeholders embedded▪

in the healthcare system for better outcome and better society– Government from loosening the fiscal constraints & strains on the healthcare system– Patients from better quality of life
– Physicians from better care solution for patients– Academia from enhanced scientific talent development– Overall economy from GDP and job creation– The entire Japan as country from the enhanced Japanese players’ global presence and the attention fromglobal companies
To achieve this all “win-win” to the society, Japanese government should continue to encourage and facilitate| 34
the innovation in healthcare and pharmaceuticals

Value of medicine by disease area

COPD

Diabetes

Stroke prevention in AF

Depression

CKD

| 35

COPD

Key drivers of the value of Spiriva
Japanese data available

Included in sizing

Global data available
1

Efficacy in managing core COPD symptoms and slowing down
disease progression

Efficacy in preventing complications such as heart disease

Minimizing side effects compared with other therapy (e.g.,
anticholinergic side effects)

Impact on GDP as a result of slowing
down disease progression

Others1

Reduction in family burden as a result ofbetter disease management

Improved quality of life

SOURCE: 1 Salmeterol and Fluticasone Propionate and Survival in Chronic Obstructive Pulmonary Disease, February 22,
2007, Peter M.A. Calverley, et al., N Engl J Med| 36

COPD – Population level

Overview of value of COPD medicine at the population level
Value of medicine at anindividual level
Million JP

Reductionof cost ofa medical
treatment

Male

0.03

# of potential
patientsa% seeing
doctor885,343

1.8

FemaleNumber of patients% of regular
workerb

Total value of
medicine inJapan
Billion JPY
3.0－

383,465

68.9

－

10%
Reductionb of GDP
loss

Male

Female-0.3

885,343

1.6

383,465

90%

36%

-22.8

22.5

Suppose 10%of potential~70 billion
JPY valuepatients will
see a doctora Calculated by multiplying the number of potential patients by % of each sex and % of patients whose ages are between 40 and 50, based on the data from a clinical study and MHLW..
b Calculated with the number of regular worker and the number of people in the age group (40-50).
SOURCE:「平成23年度国民経済計算確報 (フロー編)」, 「第１回今後のパートタイム労働対策に関する研究会 配付資料 資料4 パートタイム労働の現状, Labor Force Survey, Historical data 1 (2) Employed person（by age group） - Whole Japan, Monthly Data, Table 4 on MHLW’s website regarding working hours (http://www.mhlw.go.jp/toukei/itiran/roudou/jikan/syurou/11/gaiyou01.html),
UPLIFT study (http://www.uplift-study.com/ers2009/doc1.html), 「日本における慢性閉塞性肺疾患の医療経済評価モデルの構築と新規COPD治療薬チオピトロウムの費用効用分析」
Prevalence of chronic obstructive pulmonary disease in Japan : results from the NIPPON COPD epidemiology（NICE）study, Population Survey Report,「第１回今後のパートタイム労働対策に関する研究会 配付資料 資料4 パートタイム労働の現状, 「平成23年パートタイム労働者総合実態調査の概況：個人調査」, Patient research| 37

DIABETES

Key drivers of the value of Januvia
Japanese data available

Included in sizing

Global data available
1

Relationshipbetween HbA1c andprevalence rate

1

Relationshipbetween HbA1c andprevalence rate

Retinopathy
Efficacy inmanaging blood
glucose / reducing
diabetic
complications
compared with diet
+ exercise andstandard therapy

Nephropathy

Cardiovascular diseases (CVD)

For ischemic heartdisease only

For ischemic heartdisease only2

1

Neuropathy

Other pharmacological effects such as improvement in bloodpressure or lipids

Minimizing side
effects comparedwith current therapy

Limited 3

Single-arm, noncomparison and small
sample study
4

Hypoglycemia leading to complications
such as mortality

Weight gain

Impact on GDP as a result of diabetic
complications

Relationshipbetween HbA1c andprevalence rate

Limited3

For the 3 complications stated above

For the 3 complications stated above

1,2

Improved compliance due to once-a-day
dosingOthersReduction in family burden as a result ofbetter disease management

Improved quality of life

Limited3

Single-arm, noncomparison and small
sample study

SOURCE: 1 Relationship between glycated haemoglobin and microvascular complications: Is there a natural cut-off point for the diagnosis of diabetes?, C. Sabanayagam, et al., 2009, Diabetologia
2 Cardiovascular safety of sitagliptin in patients with type 2 diabetes mellitus: a pooled analysis, Engel SS, 2013, Cardiovasc Diabetol
3 Effects of sitagliptin beyond glycemic control: focus on quality of life, Yoshiko Sakamoto, et al., 2013, Cardiovascular Diabetology 2013
4 The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study, 2009, Denise E Bonds, et al., BMJ| 38

DIABETES – DPP4 inhibitor vs. αGI: Population level

Overview of value of DPP4 inhibitor compared with αGIat the population level
αGI
Billion JPY

DPP4 inhibitor
Billion JPY

Value of medicine
Billion JPY

Cost ofa medical

Cost ofb treatingcomplications

c GDP

1,008

929

treatment

1,576

1,766

218

190

2,913 bn JPY

2,775 bn JPY

SOURCE: 「最新 医療費の基本と仕組みがよ～くわかる本「[第3版]」, 「糖尿病になったらいくらかかる？」, Website of “Diabetes Net” (http://www.dm-net.co.jp/seido/02/), 「今日の治療薬 2013」, Website of 平成24年調剤報酬表(http://www1.ocn.ne.jp/~kaminote/houshuuhyou.html), メディファーマ, Incidence and progression of diabetic retinopathy in Japanese adults with type 2 diabetes: 8 year follow-up study of the Japan Diabetes Complications
Study (JDCS), 「糖尿病の医療費分析報告」, Website of Aso city(http://www.city.aso.kumamoto.jp/living/health/welfare/13-1.html#02), Low transition rate from normo- and low microalbuminuria to proteinuria in Japanese type 2
diabetic individuals: the Japan Diabetes Complications Study (JDCS), 「JDCS (Japan Diabetes Complications Study) 疫学研究・大規模臨床試験より得られたESM」, 「糖尿病と冠動脈疾患の疫学」, What is retinopathy of
diabetes?”, Website of Lions club international (http://www.lionsclubs.gr.jp/eye-health/e1/e1-2/kenko2.html), Patient research, 「ケアネット白書2012 糖尿病編」,

-79

189

28

138 bn JPY| 39

DIABETES – SU + DPP4 inhibitor vs. SU: Population level

Overview of value of DPP4 inhibitor + SU compared with SU
alone at the population level
SU
Billion JPY

SU + DPP4 inhibitor
Billion JPY

Value of medicine
Billion JPY

Cost ofa medical

Cost ofb treatingcomplications

c GDP

1,470

963

treatment

3,397 bn JPY
SOURCE:

1,692

2,166

267

-507

199

3,361 bn JPY「最新 医療費の基本と仕組みがよ～くわかる本「[第3版]」, 「糖尿病になったらいくらかかる？」, Website of “Diabetes Net” (http://www.dm-net.co.jp/seido/02/), 「今日の治療薬 2013」, Website of 平成24年調剤報酬表(http://www1.ocn.ne.jp/~kaminote/houshuuhyou.html), メディファーマ, Incidence and progression of diabetic retinopathy in Japanese adults with type 2 diabetes: 8 year follow-up study of the Japan Diabetes Complications Study(JDCS), 「糖尿病の医療費分析報告」, Website of Aso city(http://www.city.aso.kumamoto.jp/living/health/welfare/13-1.html#02), Low transition rate from normo- and low microalbuminuria to proteinuria in Japanese type 2 diabetic
individuals: the Japan Diabetes Complications Study (JDCS), 「JDCS (Japan Diabetes Complications Study) 疫学研究・大規模臨床試験より得られたESM」, 「糖尿病と冠動脈疾患の疫学」, What is retinopathy of diabetes?”, Websiteof Lions club international (http://www.lionsclubs.gr.jp/eye-health/e1/e1-2/kenko2.html), Patient research, 「ケアネット白書2012 糖尿病編」,

474

68

35 bn JPY
| 40

STROKE PREVENTION IN AF

Among the value drivers for Apixaban, improved efficacy on
stroke prevention and less bleeding incidence are key

Value drivers included in assessment

Japanese data available
Efficacy ofdrugs
comparedwith warfarin

Minimizingside effects
comparedwith warfarin

OthersIncluded in sizing

Global data available

Preventing stroke and other embolistic
events1

Reducing need for monitoring and lab tests

2

Intracranial hemorrhage

1

Other hemorrhage such as GI bleed

1

Impact on GDP as a result of disease
complications and drug-related side effects

1

For stroke andintracranial hemorrhage

For stroke andintracranial hemorrhage

Reduction in family burden as a result ofbetter disease management

Reduction in diet restriction

2

Improved quality of life2

Cost effectivenessmeasured by QALYSOURCE: 1 Apixaban versus Warfarin in Patients with Atrial Fibrillation, September 15, 2011, Christopher B. Granger, N Engl J Med
2 Cost-Effectiveness of Apixaban Compared with Warfarin for Stroke Prevention in Atrial Fibrillation, Soyon Lee, et al., 2012, PLOS ONE| 41

STROKE PREVENTION IN AF – Population level

Overview of value of Apixaban compared with Warfarin at the
population level
Warfarin
Billion JPY
Cost of drugs
a for preventing
stroke433

Cost ofmedicalbtreatment forcomplications

-974

453

1,335

395

2,985 bn JPY
SOURCE:

Value of medicine
Billion JPY

1,407

822

Cost ofmedicalctreatment forside effects

d GDP loss

Apixaban
Billion JPY

369

0

1,335

75

1,935 bn JPY

Prevalence of atrial fibrillation in the general population of Japan: An analysis based on periodic health examination, 2009, Inoue H, et al: Int J Cardiol 137; Population Survey Report, Table
3-2 and 3-3 of Appendix of Volume 1, 2011, MHLW; Prevalence clinical characteristics of patients with atrial fibrillation – Analysis of 20,000 cases in Japan-, 2000, Tomita F, et al: Jpn Circ J;
Can the relationship between endothelial function and CHADS2 score account for the pathogenesis of thromboembolism?, Terazawa H, et al, 「脳卒中患者の生命予後と死因の5年間にわたる
観察研: 栃木県の調査結果とアメリカの報告との比較」

320

1,050 bn JPY| 42

DEPRESSION

Key drivers of the value of Cymbalta
Japanese data available

Included in sizing

Global data available

Achieving remission
Efficacy ofCymbalta comparedwith placebo

1Second relapse after initial remission

Hospitalization

Suicidal rate

Data on SSRI
only

Minimizing side effects compared with placebo

2

Impact on GDP as a result of depression

Others

Effect ofCymbalta on
ability to work

Reduction in family burden as a result ofbetter disease management

Improved quality of life

SOURCE: 1. Enhancing Outcomes from Major Depression: Using Antidepressant Combination Therapies with Multifunctional Pharmacologic
Mechanisms from the Initiation of Treatment, Stephen M. Stahl, 2010, CNS Spectr; 2. Depression Treatment with Duloxetine andReduction of Inability to Work, Michael Happich, et al., 2012, Depression Research and Treatment| 43

DEPRESSION – Population level

Overall value of Cymbalta compared to placebo at population
level
Value of Cymbalta comparedto placebo at individual level
Thousand JPY
Cost oftreating
depression(Direct cost)

-102

-51

GDP loss(Indirect
cost)

Medicaltreatment
cost forside effects

Value of Cymbalta comparedto placebo at population level
Billion JPY

499-873~0134～217~080~165 bn JPY

SOURCE:「精神障害による休業者に関する調査 」, Table 4 on MHLW’s website regarding working hours (http://www.mhlw.go.jp/toukei/itiran/roudou/jikan/syurou/11/gaiyou01.html), 「平成23年度国民経済計算確報 (フロー編)」, 「第１回今後のパートタイム労働対策に関する研究会 配付資料 資料4 パートタイム労働の現状, Labor Force Survey, Historical data 1 (2) Employed person （by age group） - Whole Japan, Monthly Data, Patient research, 「病気にかかるおカネ」, 「今日の治療薬 2013」,うつ病の病態・診断・治療, (http://www-yaku.meijo-u.ac.jp/Research/Laboratory/chem_pharm/09jugyou/101203lecture.pdf),「Duloxetineの特徴 – 国内第3相比較試験の再解析結果を中心に - 」, 「Duloxetineの大うつ病性障害に対する臨床評価- Placebo及びparoxetineを対象薬とした二重盲検比較試験 -」, 「うつ病の長期経過」

If the productive
age is extended
from 65 to 70,
the GDP impact
will become
194-314 bn JPY,
and the total
impact will
become ~140260 bn JPY
| 44

CKD

Key drivers of the value of Nu lotan
Japanese data available

Included in sizing

Global data available
1

Reducing blood pressure

Efficacy of drugs
compared withplacebo for other
CKD / non-diabetic
nephropathy
patients

Reducing the speed of GFR decline by
reducing blood pressure

2

Other renal-protective effects (e.g,reducing proteinuria)

1

1

As a result of the above, reduction in
ESRD and mortality

Efficacy of drugs in reducing other complications such as CVD

Impact on GDP as a result of disease
complications

OthersBecause most patients already passed
the productive age

1Reduction in family burden as a result ofbetter disease management

Improved quality of life

SOURCE: 1 Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy, Barry M. Brenner, et al., September 20, 2001, N Engl J Med
2 Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees
Working Group, Bakris GL, et al., 2000, Am J Kidney Dis| 45

CKD – Population level

Compared with placebo, Nu Lotan is estimated to deliver a value
Otherof ~80B JPY at the population level for CKD caused by
Diabetic nephropathy
diabetic nephropathy Value of medicine# of patients with
# Value of medicine
at individual level
Proteinuria

Age

GFR

Million JPY

30～39
Without
proteinuria

2.7

hypertension in eachgroupaat population levelb
Billion JPY

14,69722.1 17.3

3,006

2.6 2.0

50～59
15～29
60～69

1.5

15～29
40～49

50～59
With
proteinuria

30～39

7,531

2.3
3.4
1.5

2.6

30～39

7.6

16,712

32.0

6,188

5.3 4.1

5,370

15～29 -0.4

9.6

-1.3

25.2

-1.0

15,50322.6 17.7

13,453

8.1 6.3

60～69
15～29

1.1

a Calculated by multiplying # of patients in each age group by the percentage of each GFR group first based on data from MHLW1 and Japanese Society2 ofNephrology, then used percentage of hypertensive patients and patients with proteinuria from a clinical test3
b. Calculated based on epidemiology data that 44% of new ESRD patients are caused by diabetic nephropathy, Japan Society of Dialysis Therapy
SOURCE:

1 Population Survey Report, Table 3-2 and 3-3 of Appendix of Volume 1, 2011, MHLW
2 「CKD診療ガイド 2012」, 日本腎臓学会、東京医学社
3 Risk factor profiles based on estimated glomerular filtration rate and dipstick proteinuria among patients of the Specific Health Check and Guidance System in Japan 2008, 2012,
Kunitoshi Iseki, et. Al, Clin Exp Nephrol~80 bn JPY| 46