Assessing the benefit of medicine in Italy

International Public Affairs and Policy

Assessing the benefit of medicine

in Italy

May 2010


2

Innovative medicines are having a significant impact on

public health in Italy

Life expectancy

in Italy is

increasing…

… and innovative

medicines have

contributed

significantly to

this increase

However, there

remains scope

for further

improvement in

public health

Continued

innovation will

bring further

benefit to

patients

Cardiovascular disease

Diabetes

Cancer

Infectious disease

Rheumatoid arthritis

Orphan disease

Schizophrenia

However, further emphasis on innovation in Italy is needed – the proportion

of GDP spent on R&D is much lower than the European average

May 2010

Modena (2001)


3

Life expectancy in Italy is increasing

May 2010

World Bank (2010), Istat (2009)

40

45

50

55

60

65

70

75

80

85

1960

1963

1966

1969

1972

1975

1978

1981

1984

1987

1990

1993

1996

1999

2002

2005

Year

Lif

e e

xp

ec

tan

cy

Life expectancy at birth

crossed the threshold of 80

years for the population as a

whole in 2000

It is estimated that a male

born in 2008 can expect to live

79 years, and a female can

expect to live 84 years.

12 years

Countr

y-level data


4

Innovative medicines have contributed to this increase in life

expectancy

40-59% of the total increase in life expectancy across 52 countries including Italy is

attributable to innovative medicine launches. Life expectancy is continuing to increase as a

result of progress in the treatment and prevention of cardiovascular disease and cancer

Lichtenberg (2005)

0.23

0.37

0.57

0.76

0.941.07

1.21

1.37

1.531.65

1.82

1.96

0.70

0.12

0.30

0.600.7

0.06

0.21

0.380.45

0.510.56

0.62 0.660.74 0.79

0

0.25

0.5

0.75

1

1.25

1.5

1.75

2

2.25

1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000

Inc

rea

se

in

lif

e e

xp

ec

tan

cy

, y

ea

rs Total increase

Increase due to new medicines

40-59% of the

increase in

life

expectancy is

due to

innovative

medicine

May 2010G

lobal-le

vel data


5

However, there remains scope for further improvement in public

health

Istat (2009)

May 2010

Even though death rates for

most categories are falling,

mortality rates due to disease

are still high. The leading

cause of death in Italy in

2009 was cardiovascular

disease (39% of all deaths),

followed by cancer (30% of

all deaths)

Unlike other disease specific

death rates, death due to

cancer has increased over

the last 30 years

13

39

61

286

373

16

58

77

190

446

0 100 200 300 400 500

Infectious and

parasitic diseases

Diseases of the

digestive system

Diseases of the

resporatory

system

Neoplasms

Cardiovascular

disease

Death rate (deaths per 100 000 persons

2006 1971

Countr

y-level data


6

Through the continued process of innovation, further benefits can

be brought to patients

• In 2008, Italy invested approximately

1% GDP in R&D activities, which is

half of the European average of 2%

and almost 4 times less then the

European leader Sweden

• The Italian pharmaceutical industry

was ranked 5th globally for sales in

1999. However, this high level of

production and distribution is not

matched by research activities

• Therefore, investment in innovation

and R&D should be an important focus

for Italy in the future in order to

improve the countries contribution to

the industry and ultimately the

contribution to reducing disease-

related morbidity and mortality

WHO (2006), Modena (2001), Eurostat (2010)

May 2010C

ountr

y-level data


7

Cardiovascular disease

CHAPTER 1: Innovation is significantly benefiting patients with…


8

Pharmaceutical innovation has reduced cardiovascular-related

mortality

Prevention of

cardiovascular

disease

Treatment of

cardiovascular

disease

Increased

survival

Reduction in risk

factors

Pharmaceutical

innovation

Prevention and

treatment of

associated

problems

Innovative therapies are

recognised as being a

major contributor to the

observed increase in

survival and reduction in

risk factors

However, cardiovascular disease remains the leading cause of death in

Italy and there remains a significant need for innovation in the treatment of

this problem

May 2010


9

Pharmaceutical innovation has resulted in significant progress in both

the prevention and the treatment of cardiovascular disease and its

associated problems 1910-1940’s

1919 Organic

mercury causes

diuresis and is

beneficial in oedema

associated with heart

failure

1949 Sulfa drug used to

treat oedema due to

heart failure. However,

long term toxicity a

problem

Identification of

Chlorthiazide –

improved reduction of

oedema and high blood

pressure with a safer

profile

1950’s

1950

Acetazolamide

identified – 300

times more potent.

1970’s 1960’s 1980’s 1990’s 2000 and

beyond

Early 1960s

Loop diuretics

discovered (new

mechanism of

action) followed

shortly by the

potassium

sparing diuretics

Spironolactone

and Amiloride

1913 Adrenaline

found to be able to

relax and constrict

vessels – alpha and

beta receptors

identified

1958 First Beta-

blocker identified,

but initial compound

has low potency

Propanalol

identified soon after

– revolutionary as

it offers for the

first time

preventative

therapy for

asymptomatic

patients

1980s Angiotensin

converting enzymes

investigated for heart

disease. ACE

inhibitors used to

control high blood

pressure – the active

compound Captopril

discovered with

further developments

with pro-drugs such

as Quinapril

As a result further

research leads to the

discovery of the

angiotensin II receptor

with medicines

developed to block it

such as Losartan

ABPI (2004), OsMed (2009)

1950’s-60’s Medicines to treat high cholesterol first

identified but there were many unwanted side effects

1971 Start of

research into

Statin therapy by

inhibiting the

enzyme associated

with synthesis of

cholesterol

Mevastatin

identified followed

by the isolation of

the more effective

inhibitor

Lovastatin

Today – Six

statins are

available in Italy:

Atorvastatin,

Fluvastatin,

Lovastatin,

Pravastatin,

Rosuvastatin

and Simvastatin.

“The fundamental mechanisms of disease are being explored for future novel

innovative treatments to offer further patient benefits”

STATINSBETA-BLOCKERS, ACE INHIBITORS,

ANGIOTENSIN II ANTAGONISTSDIURETICS

May 2010G

lobal-

and C

ountr

y-leve

l data


10

Cancer



11

Pharmaceutical innovation has increased the likelihood of survival for

patients with cancer

Incremental

innovation

Increased

survival

Pharmaceutical

innovation

Mortality is

decreasing across a

range of cancers

despite the

increasing incidence

of disease

However, cancer remains one of the leading causes of death in Italy and

survival is varied across different cancer sites; there remains a significant

need for innovation in the treatment of this disease

Tyrosine kinase inhibitors

Monoclonal antibodies

Taxoids

Aromatase inhibitors

Novel therapies

New therapeutic

targets

e.g. colorectal cancer

e.g. prevention of cell

division

May 2010

The earlier detection

and diagnosis of

cancer has also

contributed to

increased survival in

patients with cancer


12

Cancer mortality in Italy has stabilised despite a 25% increase in the

incidence of cancer

Capocaccia (2007), Istat (2009)

May 2010

0

100

200

300

400

500

600

700

1970 1975 1980 1985 1990 1995 2000 2005Year

ca

se

s/d

ea

ths

pe

r 1

00

00

0 p

op

ula

tio

n

Incidence (male) Incidence (female) Cancer mortality

• Over the past 30

years, the mortality

rates for all malignant

neoplasms have

increased by 50%

• However, over the last

decade mortality rates

have been constant

despite rising

incidence rates

27% increase in

incidence of cancer

in males

23% increase in

incidence of cancer

in females

Constant mortality rates

Countr

y-level data


13

And increasing survival rates can be seen across a wide range of

cancers in Italy

EUROCARE (2009)

May 2010

5 7 18 20 26 32 38 40 41 42 4562 64

82

10 12 19 3044 43 54 53

7958 63 70 77 89

020406080

100

OesophagusLung

Brain

Stom

ach

Leukaemia

Multiple m

yeloma

NHL

Rectum

Prosta

teColon

Kidney

Larynx

Bladder

Testis

Ag

e s

tan

dard

ised

5 y

ear

su

rviv

al, %

1983-1985

1995-1999

MA

LE

SF

EM

AL

ES

9 1223 24 26 26

39 40 41 44 4557 64 68 72

16

4435

6556 59

76

2015

584436

8378

65

0

2040

6080

100

OesophagusLung

Brain

Leukaemia

StomachOvary

Multiple m

yeloma

Kidney

RectumColon

NHL

Cervix

Bladder

Corpus uteri

Breast

Ag

e s

tan

dard

ised

5 y

ear

su

rviv

al, %

Countr

y-level data


14

Infectious Disease



15

However, severe infectious disease remains a significant problem,

requiring innovation in both the development of effective

treatments and preventative vaccines

Pharmaceutical innovation has enhanced the prevention

and treatment of infectious disease

Prevention of

infection through

vaccination

Treatment of

infection

Reduction or

elimination of

previously

common

infections

Pharmaceutical

innovation Enhanced

survival

e.g. polio

e.g. invasive aspergillosis

Enhanced

patient

outcomes

e.g. hepatitis B

Reversal of viral

infection

damage

e.g. hepatitis C

May 2010


16 Adapted from NHS (2008)

Pharmaceutical innovation has enabled the development of

many vaccines

May 2010

1700 1800 1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000

1796

Development of the

first smallpox vaccine

1870

First live

attenuated

bacterial vaccine

1885

First live attenuated viral

vaccine

1896

Typhoid

1900s

Cholera

1950

Pertussis

BCG

1956

Inactivated

polio

1960

Influenza

1961

Tetanus

1962

Live oral polio

1942

Diphtheria

1970

Rubella

Meningococcal

A&C

polysaccharide

1976

Measles

1982

Hepatitis B

1988

MMR

1992

Hib conjugate

Hepatitis A

1999

Meningococcal

C conjugate

2001

Pneumonococcal

conjugate

2006

Combined

Hib/MenC

2008

Human

papillomavirusGlo

bal-le

vel data


17

And vaccination has reduced the incidence of many previously

common infectious diseases

Measles

Pertussis

(Whooping cough)

Salmaso (2001), Istat (1999,2001, 2002, 2005), Sorvelianza Pediatri Sentinella (2010), Rota (2005), WHO (2010), Manfredi (2005), MdS (2008)

May 2010

0

50

100

150

200

1960

1963

1966

1969

1972

1975

1978

1981

1984

1987

1990

1993

1996

1999

2002

2005

2008

Year

Incid

en

ce (

cases p

er

100,0

00 p

op

ula

tio

n)

0

20

40

60

80

100

Vaccin

e c

overa

ge (

%)

Incidence Vaccine coverage

0

10

20

30

40

50

60

1955

1958

1961

1964

1967

1970

1973

1976

1979

1982

1985

1988

1991

1994

1997

2000

2003

2006

Year

Incid

en

ce (

cases p

er

100,0

00 p

op

ula

tio

n)

0

20

40

60

80

100

Vaccin

e c

overa

ge (

%)

Incidence Vaccine coverage

Vaccine introduced in 1976

Vaccine introduced in 1960’s

“Although childhood

vaccination coverage has

increased in recent years,

reaching the national average

of 88% in 2006, it is still below

the target of 95%, and

outbreaks continue to occur.”

“Since the introduction of the

pertussis vaccine in 1962, epidemic

peaks have regularly occurred every

3–4 years… [with] decreasing

incidence and decreasing peak

height… Since 1998 no further

epidemics have been observed

although a slight increase in

incidence was reported in 2002.”

Countr

y-level data


18

But prevention through vaccination is still needed for many

serious infections

Meningitis

• Around 900 people in Italy are affected by bacterial Meningitis each year,

associated with a 14% mortality rate

• In survivors, one in seven people will be left with a permanent disability

• In the past 20 years vaccines have been developed against Haemophilus

influenzae type B (Hib) (1992), Meningitis C (1999), and Pneumococcal Meningitis

(2006), but there is no vaccine for Meningitis B – the strain accounting for

66% of all cases in Italy

HIV/AIDs

• Around 150 000 people in Italy are estimated to be living

with HIV, up from 140 000 in 2001

• The annual number of deaths due to HIV has fallen

dramatically since the introduction of HAART in 1996

• In September 2009 the discovery of a breakthrough

new vaccine was reported which may reduce the risk

of HIV by a third, however, no cure or vaccine is

currently available to treat HIV/AIDS

Istituto Superiore di Sanità (2007), WHO (2008), EU-IBIS Network (2007)

May 2010C

ountr

y-level data


19

Orphan Diseases



20

Pharmaceutical innovation has led to significant benefits

for patients with rare diseases

Challenges in

treating rare

diseases has led

to substantial

unmet need

Improved control

of symptoms

Pharmaceutical

innovation

New therapeutic

options

However, there remains a significant unmet need for innovation in the

development of therapies for orphan diseases with limited therapy options

in order to improve symptom control and survival

May 2010

Significant

number of

patients with rare

diseases

The development of

innovative

treatments for

orphan diseases is

increasing

The number of

diseases given

orphan status is

increasing

Limited therapeutic

options or no

treatments available Enhanced

survival


21

The number of diseases given orphan status is expanding, but

the number of treatments available is also increasing

May 2010

• The definition of an orphan or

rare disease in Europe is a

disease that affects 5 in

10 000 people

• Rare diseases are often

severe, chronic, progressive,

and life-threatening

• The number of rare diseases

around the world with no

treatment currently available

is estimated to be between

4000 to 5000 and still

increasing

• 27 to 36 million people are

estimated to be affected by

rare diseases in the EU

37

12

1822

30

43

49

55

0

10

20

30

40

50

60

2001 2002 2003 2004 2005 2006 2007 2008 2009

Year

To

tal o

rph

an

dru

gs

re

ce

ivin

g

ma

rke

t a

uth

ori

sa

tio

n

Orphanet (2009), EMEA (2007), EURORDIS (2005)

The development of innovative orphan drugs

to treat rare diseases has increased, offering

patients new options or treatments that were

previously unavailable

EU

-le

vel data


22

With regional strategies in place to prioritise the diagnosis

and treatment of rare disease in Italy• Rare diseases have been a priority topic in Italy since

1998

• Since 2001, rare diseases have been a priority in all

Italian National Health Plans (2003-2005, 2006-2008)

• Although there is not a single overarching national

plan, there are a series of regional plans designed to

emphasise the diagnosis and treatment of rare

diseases

• A national registry of rare diseases has been

established and there is a national research

programme

• Italy is one of only four countries (Denmark, France,

Sweden) that has dedicated centres of expertise for

rare diseases

• 36 of the 46 authorized orphan drugs are now

available for patients in Italy:

“Funding research programmes will lead to

discovery of new drugs”

May 2010

Taruscio (2008), EUROPLAN (2008), ECRD (2007)

The Ministry of Health published a

decree in 2001 that aimed at

improving the prevention,

diagnosis, and treatment of rare

diseases

The Italian National Centre for Rare

Diseases (Istituto Superiore di

Sanità) is the leading organization

in EUROPLAN, an EU-wide

initiative to develop national

strategic plans for rare diseases

Orphan drugs are a research

priority for the Italian National

Medicines Agency (AIFA), with 20

independent research proposals

funded in 2005, and 24 funded in

2006

Countr

y-level data


23

Pharmaceutical innovation provides many patient benefits

and are having a significant impact on public health in Italy

Pharmaceutical

innovation

Prevention of illness

Inhibition and reversal of

disease-related damage

Reduced disease

progression and

disease-related events

Increased survival

Improved public

health and

increased life

expectancy

Social benefits and

improved quality of life

Reduced adverse events

Increased therapeutic

options

Continued pharmaceutical innovation is vital for the continued

improvement of public health

May 2010

Documents

Assessing the benefit of medicine in Italy