the value of generics and biosimilar drugs

Dr Paul Cornes

Conflict of interest

Salary received:

• United Kingdom National Health Service

Honoraria received:

• Roche

• Janssen

• Sandoz

• Lilly

• European Generics Association

• Teva

• Hospira

Strive not to be a success,

but rather to be of value

The value of generics and

biosimilar drugs

Comparative Outcomes Group

ESO Task Force Advisory Board on

Access to Innovative Treatment in

Europe

European School of Oncology

Piazza Indipendenza, 2

6500 Bellinzona - Switzerland

Dr Paul Cornes,

Consultant Oncologist,

Bristol Haematology & Oncology Centre

[email protected]



The value of generics and

biosimilar drugs

Good news for cancer treatment:

worldwide – more people survive cancer

WHO Health for all database


Innovation in cancer drugs

<1960

5 cancer

drugs

1960s

+ 2

more

1970s

+ 18

more

1980s

+ 14

more

1990s

+ 24

more

2000s

+ 23

more

2010-13

+ 20

more in

only 3

years

At this rate our decade will add 67

new cancer drugs by 2020 !

Cornes P. Pictogram created from data in - Savage P. Development and economic trends in cancer therapeutic drugs: Analysis of

modern and historical treatment costs compared to the contemporary GDP per capita. J Clin Oncol 32, 2014 (suppl; abstr e17535)

Good news for cancer treatment

The costly war on cancer. The Economist. 2011 May 26. http://www.economist.com/node/18743951

Drugs in

development,

2010

900 drugs in

development

are for cancer


Survival impact of some targeted therapies

data from Munoz, J.et al (2012) Targeted therapy in rare cancers—adopting the orphans Nat. Rev. Clin. Oncol. doi:10.1038/nrclinonc.2012.160. Table from The

Value of Medical Innovation. http://valueofinnovation.org/a-world-free-from-cancer/#ref3, Accessed April 29, 2014

Cost of cancer drugs by year of approval

Limits on

Medicare's

ability to

control

rising

spending on

cancer

drugs

Bach P. N

Engl J Med

2009;

360:626-633

Cancer drug

costs rise 5x

faster than other

classes of

medicine

Bach P. NEJM. 2009 Feb 7

Innovation is expensive

Kaitlin KI. Deconstructing the drug development process: the new face of innovation. Clin Pharmacol & Therapeutics. 2013.

Doctors say cancer drug costs are too high. http://medicalxpress.com/news/2013-04-doctors-cancer-drug-high.html. Cited 21/06/2013

12 drugs were approved by the US

Food and Drug Administration

(FDA) for various cancer

indications in 2012

11 were priced above $100,000 per

year

Money doesn’t always buy life

Life expectancy at birth and health spend

WHO. The World Health Report 2000

3 fold variation

Money doesn’t always buy health

Relationship

between spend

and health is not

always clear

• Disability-adjusted

life expectancy

relative to health

expenditure per

capita in USD in

191 WHO member

states, 1999

• WHO. The World

Health Report

2000, p43

US Dollars

>10 fold variation

There is no evidence that spending more will

consistently improve health

Hussey PS et al. The

Association Between

Health Care Quality and

Cost: A. Ann Intern Med.

1 January

2013;158(1):27-34

We have to learn to spend better – not more!

Relationship

between survival for

colorectal cancer

and total health

expenditure, Data

from Organisation

for Economic

Cooperation and

development.

OECD, Cancer Care:

Assuring Quality to

Improve Survival.

OECD Health Policy

Studies. 2013: OECD

Publishing.

Cure rates can

vary significantly

for similar annual

per-capita

expenditure on

health

Hofmarcher, T., Jönsson, B., Wilking, N., Access to high-quality oncology care across Europe. IHE Report. 2014:2, IHE:

Lund.

The options for future health spending include

the following:

Carry on spending at current rates – postpone

the inevitable decision to contain spending

Carry on spending at current rates and improve

efficiency and productivity

• that is, buy extra time before confronting the

inevitable decision to contain spending

Align health spending growth to general, long-

term growth in the economy as a whole

• with possible adjustments to devote a

modestly greater share of GDP to health care

as GDP grows.

Untenable in the

medium term

Viable possibly

medium term

Only long term

viable option if

the state is to

provide health

care from

general

taxation

Appleby J et al. Spending on health care - How much is enough? Kings Fund 2006. URL: http://www.kingsfund.org.uk/sites/files/kf/SpendingonHealthCare.pdf. Accessed

Nov 2, 2014

How can we improve Malaysian Guidelines?

Add cost effectiveness

Cost/effectiveness

High

<1 x GDP

Moderate

1 <2 x GDP

Poor

>2 x GDP

Clinical

effect

Extremely

effective

Moderate

efficacy

Minimal

efficacy

For debate – we propose this for the

2014-2015 guidelines

We hope to agree

MOH funding for

these



Cost/effectiveness

High

<1 x GDP

Moderate

1 <2 x GDP

Poor

>2 x GDP

Clinical

effect

Extremely

effective

Moderate

efficacy

Minimal

efficacy

We hope to agree

MOH funding for

these



Cost/effectiveness

High

<1 x GDP

Moderate

1 <2 x GDP

Poor

>2 x GDP

Clinical

effect

Extremely

effective

Moderate

efficacy

Minimal

efficacy

We hope to agree

MOH funding for

these

Push for generics, biosimilars, price

reductions or cheaper

dose/schedules to bring expensive

treatment inside MOH funding zone

Release value from current programme with

generics, biosimilars, or cheaper

dose/schedules to free-up resource

And reinvest the

savings into

innovative care

Bad news for cancer

Elkin EB, Bach PB. Cancer's next frontier: addressing high and increasing costs. JAMA 2010;303:1086-1087.

Meropol NJ, Schrag D, Smith TJ, et al. American Society of Clinical Oncology guidance statement: the cost of cancer care. J Clin Oncol 2009;27:3868-3874.

Richard Sullivan et al –

Lancet Oncology, 2011;12(10):933-980

Classes of treatments to target for cost-effective

care

Ref: Sullivan R et al. Delivering affordable cancer care in high-income countries. Lancet Oncol 2011;12:933

Richard Sullivan et al –

Lancet Oncology, 2011;12(10):933-980

Equally effective but cheaper treatment

WHO – World Health Report 2010

All countries can do

something, many of

them a great deal, to

improve the efficiency

of their health systems,

thereby releasing

resources that could be

used to cover more

people, more services

and/or more of the

costs.

Ref WHO. World health report 2010.Chapter 4: More health for the money. URL: www.who.int/whr/2010/10_chap04_en.pdf. Accessed OCT 29, 2014

Ten leading causes of

inefficiency

Education to promote cost-effective care

Wagstaff A. Cancer World 2007 March/April p24-28

“billions of euros are wasted,

say researchers, because

doctors prescribe branded

drugs when a generic

equivalent is just as good”

Response to cost constraints in medical

treatment: generic substitution

Generic drugs are

chemically identical

copies of older drugs

that have lost patent

protection

Drug makers save on both development

and clinical trial testing costs and so can

sell the same drug cheaper

Response to cost constraints in cancer

treatment: generic substitution

In the USA, each 1% increase in generic prescribing reduces

drug costs by $1.32 billion annually

– Privitera MD. Generic antiepileptic drugs: current controversies and future

directions Epilepsy Curr 2008; 8: 113–7

UK, the average cost of a generic is a quarter of the original

brand (£4.83 and £19.33 respectively)

– www.britishgenerics. co.uk/marketkeyfacts.htm

Drug makers save on both development

and clinical trial testing costs and so can

sell the same drug cheaper

US FDA study shows generic competition is

associated with lower drug prices

Analysis of IMS retail sales data for single-ingredient brand name and generic drug

products sold in the U.S. from 1999 through 2004

http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm129385.htm

The more manufacturers make a drug – the lower the price

relative to the original branded pharmaceutical

USA – increasing generic use year on year

IMS. The Use of Medicines in the United States: Review of 2011. April 2012.

http://www.imshealth.com/ims/Global/Content/Insights/IMS%20Institute%20for%20Healthcare%20Informatics/IHII_Medicines_in_U.S_Report_2011.pdf. Accessed June 28, 2014 ---

http://americannewsreport.com/generic-drugs-saved-consumers-1-trillion-8815263 Wyatt E: Justices to take up generic drug case. New York Times, December 8, 2012:B1

Generics are now dispensed 94% of

the time where a generic form is

available

1 trillion dollars in 100 dollar notes looks like

http://www.kiplinger.com/article/business/T043-C000-S001-14-ways-to-spend-1-trillion.html Cited 1 July 2013

http://americandigest.org/mt-archives/5minute_arguments/the_awesome_awfulness_of.php. Cited 1 July 2013

Generic drug savings

Generic drug savings in the USA

• $1.06 trillion in savings over the past 10 years

Wyatt E. Justices to Take Up Generic Drug Case. New York Times December 7, 2012. http://www.nytimes.com/2012/12/08/business/justices-to-take-up-

generic-drug-case.html?_r=0. Accessed Sept 22, 2014. What Would $1 Trillion Buy?. http://www.creditscore.net/trillion-dollars/. Accessed Spet 22, 2014

Generic drug savings

Generic drug savings in the USA

• $1.06 trillion in savings over the past 10 years

Wyatt E. Justices to Take Up Generic Drug Case. New York Times December 7, 2012. http://www.nytimes.com/2012/12/08/business/justices-to-take-up-generic-drug-

case.html?_r=0. Accessed Sept 22, 2014. What Would $1 Trillion Buy?. http://www.creditscore.net/trillion-dollars/. Accessed Spet 22, 2014. Marc Siegel. The Doctor

Drought. Forbes. December 4, 2009. URL: https://archive.today/ubHNu. Accessed Nov 6, 2014

Savings translate to sustainable funding of about

700,000 family physicians for the USA

The American

Academy of Family

Physicians predicts a

shortage of 40,000

primary care doctors

(including family

practice, internal

medicine, pediatrics

and

obstetrics/gynecology)

by 2020

Generics bring treatments into reimbursement

that might otherwise be unaffordable

Shrank WH, The use of generic

drugs in prevention of chronic

disease is far more cost-

effective than thought, and may

save money. Health Aff

(Millwood). 2011 Jul;30(7):1351-

7

$52,983 / QALY

$7,753 / QALY

Branded

Generic

Shrank WH, The use of generic drugs in prevention of chronic disease is far more cost-effective than thought, and may save money.

Health Aff (Millwood). 2011 Jul;30(7):1351-7.

Where could we save the costs we need for

novel therapies?

Always look to emulate current best practice

Use of generics in volumes and values differs

by country within the EU

Generic Market Shares in Europe 2006

4 EU countries

achieve 2/3 or more

generic prescriptions

European Generic Medicines Association. http://www.egagenerics.com/doc/fac-GxMktEur_2006.pdf

Top ten drugs – the potential to save by increased use

of generics: Simoens and De Coster, 2006

They estimated that, even at the current price of generics, there are savings to be made ranging from:

• 48% in Denmark

• 47% in Germany

• 42% in Portugal and Belgium

• 41% in the Netherlands

• 35% in France

• 33% in Spain and the UK

• 31% in Italy

• 27% in Austria

• 21% in Poland

Speed of uptake of generics differs by country

within the EU

Sheppard A. Generic Medicines: Essential contributors to the long-term health of society. IMS HEALTH, London, UK

Access to innovative drugs differs by country

within the EU

Controlling costs with

generics and biosimilars

permits access to

innovation

Response to cost constraints in cancer

treatment: biosimilar medicine use

Biosimilar drugs are

chemically similar (but

not identical) copies

of older

biopharmaceutical

drugs that have lost

patent protection

Drug makers save on only development costs – as clinical

trial testing is needed to check for safety and efficacy

But even moderate cost savings of high cost drugs could

represent a significant budget saving for hospitals

Biosimilars

“Biosimilar” is a regulatory term

Refers to drugs regulated by the

EMEA which are similar biologic

medicinal products

• USA term – “follow-on biologics”

Do not refer to unregulated copy

drugs

Are marketed on expiry of the original

patent medicine

This saves drug discovery costs –

and so biosimilars are frequently sold

cheaper than the original agent

http://www.ema.europa.eu/docs/en_GB/document_library/Medicine_QA/2009/12/WC500020062.pdf

Defining a biosimilar

The World Health Organization:

• A biotherapeutic product which is similar in terms of quality,

safety and efficacy to an already licensed reference

biotherapeutic product.

– World Health Organization. Expert Committee on Biological Standardization.

Guidelines on Evaluation of Similar Biotherapeutic Products (SBPs). World

Health Organization. [Online] October 23, 2009.

http://www.who.int/biologicals/areas/biological_therapeutics/BIOTHERAPEUTIC

S_FOR_WEB_22APRIL2010.pdf.

EMA - requirements for authorisation of

biosimilar medicines

reference medicinal product (RMP) characterisation

structural, physicochemical, and biological methods

should be applied to detect even “slight differences” in

all relevant quality attributes affecting safety and efficacy

safety, clinical comparability in efficacy, PK,PD

safety, clinical, comparable efficacy to RMP

immunogenicity and pharmacovigilance

regulatory affairs

R&D

Pre clinical

Phase 1 clinical

trial

Phase 3 clinical

trial

Phase 4 / PM

surveillance

EMA approval

Current European approved 'biosimilar'

medicines - 2013

Somatropin - Human Growth Hormone

Epoetin-alfa & zeta

Filgrastim

InflixiMab

Both could save costs in cancer medicine:

• by offering a discounted cost

• by reducing the cost of the branded biologic through

competition

EMEA Special topic. Biosimilar medicines.

www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/document_listing/document_listing_000318.jsp&mid=WC0b01ac0580281bf0

2 classes of drug - potentially useful to manage

anaemia and neutropaenia in oncology

1st in class – Biosimilar Monoclonal

Biosimilar medicines

Sellinger K-H, Wessel R, Biosimilars in an Individualized Therapeutics World – The Challenge in Oncology in Life Science in the Capital Market –

Biosimilars, Deutsche Vereinigung für Finanzanalyse und Asset Management. Page 55. Accessed at

http://www.dvfa.de/files/die_dvfa/publikationen fachbuecher/application/pdf/dvfa_biosimilars_2010.pdf, Jan 21, 2013.

Time to consider biosimilar use is now – the number and value of

biologic drugs set to lose patent protection per year to 2015

suggests rapid savings may be gained to reinvest in better care

4 Significant Cancer

Biologic drugs that

we want for universal

Malaysian MoH

coverage will lose

patent protection

Imatinib

Trastuzumab

Rituximab

Peg-filgrastim

Biosimilar use is increasing

UK - White cell growth factors - G-CSF

• 80% of prescriptions written were for biosimilar versions by

the end of 2008

Germany - red cell growth factors, erythropoetins

• 65% of prescriptions written were for biosimilar versions

http://www.gabionline.net/Reports/Biosimilars-use-in-Europe. Sheppard A. Generic Medicines: Essential contributors to the long-

term health of society. IMS HEALTH, London, UK

Suggests that as

before with generic

medicines, some

countries are better

at controlling costs

than others


Uptake of biosimilar

white cell growth

factors - G-CSF since

introduction in the EU

– IMS Health. Shaping the

biosimilars opportunity: A

global perspective on the

evolving biosimilars

landscape. December

2011.

http://www.imshealth.co

m/ims/Global/Content/Ho

me%20Page%20Content

/IMS%20News/Biosimilar

s_Whitepaper.pdf

Generics bring treatments into reimbursement


Shrank WH,The use of generic drugs in prevention of chronic

disease is far more cost-effective than thought, and may save

money. Health Aff (Millwood). 2011 Jul;30(7):1351-7

$52,983 / QALY

$7,753 / QALY

Branded

Generic

Shrank WH, The use of generic drugs in prevention of chronic disease is far more cost-effective than thought, and may save money.

Health Aff (Millwood). 2011 Jul;30(7):1351-7.

Biosimilars bring treatments into reimbursement


Trends in use of white cell growth factors - G-CSF before and

after biosimilar introduction in the EU– IMS Health. Shaping the biosimilars opportunity: A global perspective on the evolving biosimilars

landscape. December 2011. http://www.imshealth.com/ims/Global/Content/Home%20Page%20Content/IMS%20News/Biosimilars_Whitepaper.pdf

Savings from biosimilars - Sweden

Skane University Hospital in Sweden

Annual saving of €650,000 (6 million SEK )

From Switching to biosimilar Human Growth

Hormone Omnitrope from the original biologic,

Somatropin

Carl-Erik Flodmark et al. Switching From Originator to Biosimilar Human Growth Hormone Using Dialogue Teamwork: Single-Center Experience From

Sweden. Biol Ther (2013) 3:35–43. DOI 10.1007/s13554-013-0011-z

With no loss of

efficacy

With no no serious

or unexpected

adverse drug

reactions

Savings from biosimilars - UK

University College London Hospitals NHS Trust also indicate the

substantial cost savings possible when switching all patients in

a single center from originator rhGH to biosimilar rhGH, with

annual savings estimated as in excess of £200,000 / Euro 240,000

– Thakrar K, Bodalia P, Grosso A. Assessing the efficacy and safety of Omnitrope.

Br J Clin Pharm. 2010;2:298–301

Thakrar K, Bodalia P, Grosso A. Assessing the efficacy and safety of Omnitrope. Br J Clin Pharm. 2010;2:298–301

annual savings from one

drug alone >£200,000 /

Euro 240,000

Savings from biosimilars - London

Savings from Biosimilar G-CSF switch in London

G-CSF purchasing cost £3.3 million per year in

2010

– Antony Grosso, London Procurement Programme,

September 2012, quoted in Pere Gascón et al. Support

Care Cancer. 2013; 21: 2925–2932. Published online 2013

August 1. doi: 10.1007/s00520-013-1911-7

£2 million saving from Biosimilar

switch predicted by 2012

Evidence that biosimilar savings are real

Aapro M, Cornes P, Abraham I. J Oncol Pharm Practice 2011 In press

white cell growth

factors can prevent

neutropaenic

septicaemia during

cancer

chemotherapy

in 2012 we now have a choice

-long acting Neulasta®

-short acting Neupogen®

-short acting biosimilar GCSF

Weighted average cost of G-CSF treatment

across five European countries

Cost of one dose based on

public pack prices for the

five EU G5 countries

Average cost weighted using

the proportional population

coefficients for each country

Weighted unit dose price inputs:

Biosimilar GCSF 300 g = €95.46

Neupogen® 300 g = €128.16

Neulasta® 6 mg = €1414.96

UK public pack price converted to € using exchange rate Sept 2010: £1 = €1.617

Aapro M, Cornes P, Abraham I. Comparative cost-efficiency across the European G5 countries of various regimens

of filgrastim, biosimilar filgrastim, and pegfilgrastim to reduce the incidence of chemotherapy-induced febrile

neutropenia. J Oncol Pharm Practice 2011 In press

Comparative costs associated with estimates of

treatment duration across three tumour types

€620

€833

€1415

€582

€782

€1415

€410

€551

€1415

Biosimilar GCSF

Neupogen®

Neulasta®

Un

it d

os

e c

os

ts (

€)

Costs based on treatment duration estimates from Weycker D. Ann Pharmacother 2006;40:402-7.

Suggests

biosimilar

drug will

deliver real

life economies

in common

cancers

Data from UK indicates biosimilars expand

access to G-CSF

2010200920082007

UK G-CSF volume growth Percent change vs. previous year

UK

Sept 2008

Biosimilar

G-CSF

approved

Pere Gascón et al. Support Care Cancer. 2013; 21: 2925–2932. Published online 2013 August 1. doi: 10.1007/s00520-013-1911-

7

Data from UK indicates biosimilars expand

access to G-CSF

2010200920082007

UK G-CSF volume growth Percent change vs. previous year

UK

Biosimilar G-CSF filgrastim

use has surpassed

Neupogen in UK

Suggests biosimilar drug

will deliver real life

improvements in the

quality of care

Sept 2008

Biosimilar

G-CSF

approved

• Physicians were able to

rewrite treatment

algorithms increasing

primary prophylaxis due

to affordability

Pere Gascón et al. Support Care Cancer. 2013; 21: 2925–2932. Published online 2013 August 1. doi: 10.1007/s00520-013-1911-7. McCamish M et al.

The State of the Art in the Development of Biosimilars. Clinical Pharmacology & Therapeutics (2012); 91 3, 405–417. doi:10.1038/clpt.2011.343

Biosimilars improve the standard of care

Walsh K. Biosimilars’ utilization and the role payers do play in driving uptake in Europe: an industry perspective.

Biosimilar Medicines 11th EGA International Symposium, April 2013. Accessed 5th March, 2014

Nearly twice as many

patients treated after

biosimilars introduced


Uptake of biosimilar

white cell growth

factors - G-CSF since

introduction in the EU

– IMS Health. Shaping the

biosimilars opportunity: A

global perspective on the

evolving biosimilars

landscape. December

2011.

http://www.imshealth.co

m/ims/Global/Content/Ho

me%20Page%20Content

/IMS%20News/Biosimilar

s_Whitepaper.pdf

Biosimilars bring treatments into reimbursement


Trends in use of white cell growth factors - G-CSF before and

after biosimilar introduction in the EU– IMS Health. Shaping the biosimilars opportunity: A global perspective on the evolving biosimilars

landscape. December 2011. http://www.imshealth.com/ims/Global/Content/Home%20Page%20Content/IMS%20News/Biosimilars_Whitepaper.pdf

Biosimilars improve the standard of care

% of G-CSF as biosimilars vs Neupogen in Europe, Feb 2013

Source: IMS MIDAS, Feb 2013, quoted in - Walsh K. Biosimilars’ utilization and the role payers do play in driving uptake in Europe: an

industry perspective. Biosimilar Medicines 11th EGA International Symposium, April 2013. Accessed 5th March, 2014

But not all

European Countries

access the benefits

equally

Savings drive increased access to treatment

Savings from Biosimilar G-CSF switch in

Southern Health Care region in Sweden

(population 1.7 million)

But still net savings of €2 million

fivefold increase in daily G-CSF usage

This represents a saving of 4–5 % of

the total drug budget

Pere Gascón et al. Support Care Cancer. 2013; 21: 2925–2932. Published online 2013 August 1. doi: 10.1007/s00520-013-1911-

7

Cost saving steps with expensive drugs can

compromise outcomes

Prescription data of statutory health insurance members in

Germany with G-CSF prescriptions between January 2008 and

July 2010 were evaluated (originator filgrastim, n = 8726;

biosimilar filgrastim, n = 4240)

– Hadji et al. Int J Clin Pharmacol Ther. 2012;50:281-9.

Approximately, ¾ of

patients received 30 million

IU dose (recommended for

body weight up to 60 kg)

Average body weight of

German adult (German

Federal Statistical Office) is

75.6 kg

Duration of G-CSF use may affect the quality of

care

5

0

≥ 7 days of

NEUPOGEN

(Mean = 10.1 days)

10

20

15

<7 days of

NEUPOGEN

(Mean = 4.7 days)

Incidence of febrile neutropenia in patients

receiving secondary prophylaxis

Scott J Managed Care Pharmacy 2003

Seven or more days of

filgrastim leads to

better outcomes

65% risk reduction

Suggests a more

affordable drug could

again improve the

quality of care


Estimated biosimilar market

potential: 2009 value of products

whose patents expected to expire

between 2009‐2019. In absolute

value

Rovira J et al, for the European

Commission (Directorate-General for

Enterprise and Industry) - The impact of

biosimilars’ entry in the EU market.

http://ec.europa.eu/enterprise/sectors/healt

hcare/files/docs/biosimilars_market_01201

1_en.pdf

Potential EU savings from biosimilar use

Höer A. Saving money in the European healthcare systems with

biosimilars. GaBI Journal 2012;1(3-4):120-6

Methods: using a sequential approach, we calculated the savings

through the use of biosimilars for France, Germany, Italy,

Poland, Romania, Spain, Sweden and UK

Results:

• The use of biosimilars is expected to result in overall savings

between Euros 11.8 billion and Euros 33.4 billion between

2007 and 2020, with largest savings expected for France,

Germany and UK.

• Biosimilar monoclonal antibodies - 1.8 to 20.4 billion Euros

• Biosimilar erythropoietins - 9.4 to 11.2 billion Euros

• Biosimilar GCSF - 0.7 to 1.8 billion Euros

Potential USA savings from biosimilar use

Predicts 378 Billion USD

saved by 2029

Shapiro RJ, Singh K, Mukim M. The Potential American Market for Generic Biological Treatments and the Associated Cost Savings,

February 2008. http://www.sonecon.com/docs/studies/0208_GenericBiologicsStudy.pdf

"...generic versions of the top 12 categories of biologic

treatments with patent protections that have expired or

that are due to expire in the near future could save

Americans $67 billion to $108 billion over 10 years

and $236 billion to $378 billion over 20 years."

Dr. Robert J. Shapiro,

former Under Secretary

of Commerce - report

released February 11,

2008http://www.youtube.com/watch?v=g

AW56_4gxS8

The predicted savings from biosimilars makes

them a priority for cost-effective care

Paul Cornes. The economic pressures for biosimilar drug use in

cancer medicine. Targ Oncol (2012) 7 (Suppl 1):S57–S67. DOI

10.1007/s11523-011-0196-3

• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291824/pdf/115

23_2011_Article_196.pdf"...generic versions of the top 12 categories of biologic

treatments with patent protections that have expired or

that are due to expire in the near future could save

Americans $67 billion to $108 billion over 10 years

and $236 billion to $378 billion over 20 years."

Cisplatin – a key cancer drug

Cisplatin – a key cancer drug

Question: Do any hospital pharmacists here believe that the

oncology physicians that they work with know the brand of

cisplatin used in your hospital?

Only 17% of US

physicians know their

own FDA Food and

Drug Administration

standards for

bioequivalency in

generic drugs

Between

80% and

125% of

that of the

innovator

product

permitted

FDA survey:

average difference

= 3.5%:

same as batch to

batch variation in

innovator

medicine

Banahan Bf, 3rd; Kolassa, EM (1997). "A physician survey on generic drugs and substitution of critical dose medications". Archives of internal medicine 157 (18): 2080–8.. Davit et al. Comparing generic and innovator drugs: a review of 12 years of bioequivalence data from the United States Food and Drug Administration. Ann Pharmacother. 2009;43(10):1583-97

Why don’t physicians know this?

“This is a role which

encompasses the

entire way in which

medicines are selected,

supplied, quality

assured, prescribed,

and administered”

Questions and answers

on generic medicines @ http://www.ema.europa.eu/docs/en_GB/doc

ument_library/Medicine_QA/2009/11/WC50

0012382.pdf

http://www.ema.europa.eu/docs/en_GB/document_library/Medicine_QA/2009/11/WC500012382.pdfhttp://www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/document_listing/document_listing_000318.jsp&mid=WC0b01ac0580281bf0

Biosimilar medicines @ http://www.ema.europa.eu/ema/index.jsp?curl=pages

/special_topics/document_listing/document_listing_0

00318.jsp&mid=WC0b01ac0580281bf0

Because we trust our

colleagues trained to

do this

Because we trust

Europe’s drugs

regulator

Physician understanding of biosimilars

USA NCCN conference respondents were asked to rate their

overall familiarity with developments for biosimilars (n = 277)

Edward C. Li.

Biosimilars: More

Education Is

Needed

http://www.nccn.org/

about/news/ebulleti

n/2011-04-

18/biosimilars.asp

22%, Only 1 in 5

moderately or

extremely familiar

with the issue

In a survey of 470 European prescribers

• France, Germany, Italy, Spain and UK

a quarter of participants cannot define or have not heard about

biosimilars before.

Only 22% consider themselves as very familiar with them

Physicians’ knowledge of biosimilars

remains insufficient:

ASBM European physicians survey on biosimilars: key findings on knowledge, naming, traceability and physicians’ choice.

http://www.europabio.org/sites/default/files/report/asbm_european_physicians_survey_on_biosimilars-_ex_summary.pdf. Accessed May 12th,

2014

http://www.bloomberg.com/news/2014-03-18/a-quarter-of-doctors-in-

europe-can-t-define-biosimilars.html

Physicians’ knowledge of biosimilars remains

insufficient:

biosimilars hold appeal for the

three primary stakeholders:

payers, physicians, and patients.

Payers are carefully monitoring

the budget impact of costly

biologics especially in high-

scrutiny areas such as

inflammation or oncology.

• The addition of cheaper

biologics in the form of

biosimilars to their formularies

therefore represents a

compelling alternative to

historically costly treatments.

Morisot S et al. Developing a Biosimilar Defense Strategy. http://obroncology.com/obrgreen/print/Developing-a-Biosimilar-

Defense-Strategy. Accessed July 1, 2014

Physicians’ knowledge of biosimilars remains

insufficient:

physicians will demand tolerability

and immunogenicity data and

long-term safety data supporting

clinical equivalence before making

prescribing decisions favorable to

biosimilars rather than reference

products.



Policies to delay biosimilar use




“Once a defensive strategy

has been determined for the

brand, it will then be

necessary to identify tactics

that will support execution of

the strategy”

For example, one of the

clinical messages that a

branded product has that a

biosimilar does not is real-

world safety data. The years

the brand product has been

used by physicians should

count for something in the

minds of stakeholders.




“While the clinical trial data

may show that the biosimilar

product is just as efficacious

and just as safe, the brand

product could have a decade

of real-world evidence of its

safety and efficacy behind it”.

An objection handler kit can

also be developed to help the

field force address objections

when comparing the brand

with biosimilars.




Many unknowns surround

biosimilars, and as a result, it

is possible to influence key

stakeholders or leverage

insecurity in the marketplace.




“efforts to undermine

trust in these products

are worrisome and

represent a disservice to

patients who could

benefit from these lower-

cost treatments.”

• FDA commissioner

Margaret Hamburg

Calvo P. Biosimilar biologics: is the US being left behind?. World Intellectual Property review. 1/11/2013.

http://www.worldipreview.com/article/biosimilar-biologics-is-the-us-being-left-behind. Accessed July 1, 2014

Editorial. Building a wall against

biosimilars. Nature Biotechnology

2013;31(4):264

Quality of biosimilar medicines

Brinks V, et al. Quality of original and biosimilar epoetin

products. Pharm Res. Published online: 01 October 2010. Doi:

10.1007/s11095-010-0288-2

Review of all published data on switching

between originator and biosimilar

Ebbers HC et al. The safety of switching between therapeutic proteins. Expert Opin Biol Ther 2012;12(11):1473-85

12,039 patients in

58 clinical trials

193 Post Authorisation Adverse event

reports from EU DRA Vigilance

Review of all published data on switching

between originator and biosimilar

Ebbers HC et al. The safety of switching between therapeutic proteins. Expert Opin Biol Ther 2012;12(11):1473-85

12,039 patients in

58 clinical trials

193 Post Authorisation Adverse event

reports from EU DRA Vigilance

Human Growth Hormone –

no safety signals

Epoetin – no safety signals

G-CSF – no safety signals

Substitution & Switching

There is a worry that switching between

Innovator and Biosimilar drugs during a

single cause of treatment could

significantly increase the risks of adverse

events

Trials to support switching may be crucial

for the concerns of some physicians and

patient groups

In the USA it may earn the registration as

an “Inter-changable” biosimilar.

Ref:

Substitution & Switching

Plantera trial design: CTP13 Biosimilar vs originator reference

Ref: Yoo DH et al. Efficacy and Safety of CT-P13 (Infliximab biosimilar) over Two Years in Patients with Rheumatoid Arthritis: Comparison Between Continued CT-P13

and Switching from Infliximab to CT-P13. ACR Abstract:#L1. URL: https://ww2.rheumatology.org/apps/MyAnnualMeeting/AbstractPrint/39033. Accessed Nov 13, 2014

R

a

n

d

o

m

i

s

e

Infliximab

Originator

Infliximab

BiosimilarInfliximab

Biosimilar

Infliximab

Biosimilar

Randomise

patientsSwitch

Year 1 Year 2

“switching” trialClassic Biosimilar trial

Substitution & Switching: Plantera trial

Response: by ACR20/50/70



Response

Week 54 Week 78 Week 102

Arm 1 Original Biosimilar Biosimilar

Arm 2 Biosimilar Biosimilar Biosimilar

Randomise Switch


Response: by ACR20/50/70



Response


Arm 1 77.5%/50.0%/23.9% 78.2%/47.9%/29.

6%

72.2%/48.3%/24.

5%

Arm 2 76.8%/45.7%/21.9% 71.5%/48.3%/24.

5%

71.8%/51.4%/26.

1%

No difference


Anti-drug antibodies present



Response


Arm 1 49.3% 49.6% 49.6%

Arm 2 49.1% 50.4% 46.4%

No difference

Substitution & Switching:

Ref PIONEER Trial. URL: http://clinicaltrials.gov/show/NCT01519700. Accessed Nov 7, 2014

Substitution & Switching - Pioneer

Pioneer trial: GCSF for chemotherapy induced neutropaenia.

During TAC chemotherapy for breast cancer

Biosimilar filgrastim – EP2006 VS Original reference drug

neupogen


Randomise

Chemotherapy cycles

Trial

Arm

1 2 3 4 5 6





neupogen


Randomise

Chemotherapy cycles

Trial

Arm

1 2 3 4 5 6

A EP2006 EP2006 EP2006 EP2006 EP2006 EP2006

2

3

B Original Original Original Original Original Original

Classic Biosimilar trial





neupogen


Randomise

Chemotherapy cycles

Trial

Arm

1 2 3 4 5 6

1 EP2006 EP2006 EP2006 EP2006 EP2006 EP2006

2

3

4 Original Original Original Original Original Original





neupogen


Randomise

Chemotherapy cycles

Trial

Arm

1 2 3 4 5 6

1 EP2006 EP2006 EP2006 EP2006 EP2006 EP2006

2 EP2006 Original EP2006 Original EP2006 Original

3 Original EP2006 Original EP2006 Original EP2006

4 Original Original Original Original Original Original

“switching” trial

Pioneer has closed on the trials

database: Results expected soon!

Cancer isn’t alone in finding a use for biologic

drugs

http://ard.bmj.com/content/72/3/315.extracthttp://bmctoday.net/practicaldermatology/2011/05/article.asp?f=what-you-need-to-know-about-biosimilarshttp://ndt.oxfordjournals.org/content/21/suppl_5/v4.full

How to promote generic use?

Moon J et al. Different initiatives across Europe to enhance losartan utilisation post generics: impact and implications. Frontiers in Pharmacology 2014;5:

Number00219. doi: 10.3389/fphar.2014.00219.

URL=http://www.frontiersin.org/Journal/Abstract.aspx?s=858&name=pharmaceutical_medicine_and_outcomes_research&ART_DOI=10.3389/fphar.2014.00219

The approach that a healthcare system or

country takes can significantly influence

the savings generated

Between 2008 and 2013, the global annual

sales of medicines losing their exclusivity

was US$50 to 100billion (€35 – 70billion),

reaching US$255billion by 2016 (1-3)

Moon JC et al, 2014

• Compared different approaches taken in

Europe to loss of Losartan exclusivity

(the first angiotensin receptor blocker

[ARB] to be approved and marketed)

How to promote generic use?

Renin-angiotensin inhibitor drugs had global sales of

US$27.3billion in 2010, 24% in Europe, much of this for single-

sourced angiotensin receptor blockers (ARBs)

– Informatics. IIfH. The Global Use of Medicines: Outlook through 2015

http://www.imshealth.com/deployedfiles/ims/Global/Content/Insights/IMS%20Inst

itute%20for%20Healthcare%20Informatics/Global_Use_of_Medicines_Report.pd

f May 2011

Broadly speaking, all angiotensin converting enzyme inhibitors

(ACEIs) and angiotensin receptor blockers (ARBs) are seen as

having similar effectiveness for the management of hypertension

and heart failure at appropriate dose titration

– Voncina L. Expert review of pharmacoeconomics & outcomes research.

2011;11(4):469-79

Patients in the UK have also been successfully switched

between different ARBs without compromising care

– Moon JC, Flett AS, Godman BB, Grosso AM, Wierzbicki AS. Getting better value

from the NHS drug budget. BMJ (Clinical research ed). 2010;341:c6449Moon J et al. Different initiatives across Europe to enhance losartan utilisation post generics: impact and implications. Frontiers in Pharmacology 2014;5:

Number00219. doi: 10.3389/fphar.2014.00219.


Why don’t all countries get the savings generics

can offer?

Losartan was the first Angiotensin receptor Blocker (ARB)

• Generics cost 10% of the original price


Number00219. doi: 10.3389/fphar.2014.00219.


Denmark switched >90% of its

patients on other ARBs to

generic Losartan

Sweden switched almost none

Spain switched almost none

% utilisation of losartan versus

all single ARBs (DDD basis)

before and after the availability

of generic losartan (Time 0) on

a monthly basis


can offer?

Denmark

• delisted all other ARBs for reimbursement

• Patients could still be prescribed another ARB and have this

reimbursed. However, the prescribing physician has to justify

the rationale to the authorities and have the explanation

accepted before other ARBs can be reimbursed. Otherwise

patients are subject to 100% co-payment

Spain

• No specific action

Sweden tried

• Physician education and leadership

• Devolved the budget to physicians for them to realise the

savings

• Even set prescribing targets e.g. % losartan as a % of all ARBs


Number00219. doi: 10.3389/fphar.2014.00219.



can offer?

Denmark

• increased ARB use by 16%

• Saved 77% in overall ARB

expenditure

• Giving €40 million each year

back to the Danish health

system

Denmark is 5.6 million of the EU

population of 503 Million

• The whole EU savings could be

40 x (503 Million/5.6 Million) =

3.6 Billion Euros


Number00219. doi: 10.3389/fphar.2014.00219.


Image:

http://upload.wikimedia.org/wikipedia/commons/thumb/5/59/Member_States_of_the_European_Union_(polar_stereographic_projection)_EN.svg/359

px-Member_States_of_the_European_Union_(polar_stereographic_projection)_EN.svg.png

WHO – World Health Report

All countries can do

something, many of

them a great deal, to

improve the efficiency

of their health systems,

thereby releasing

resources that could be

used to cover more

people, more services

and/or more of the

costs.

Ref WHO. World health report 2010.Chapter 4: More health for the money. URL: www.who.int/whr/2010/10_chap04_en.pdf. Accessed OCT 29, 2014


inefficiency

Proposal: Malaysian National Cancer

reimbursement Guidelines

That we follow the advise of the

Lancet Commission on Costs in

Oncology and the WHO 2010

report into increasing the cost

effectiveness of care


inefficiency


reimbursement Guidelines 2015

That we release value from within the current cancer drug budget

to reinvest in innovative cancer therapies

That we adopt the Danish National Health Service model for

promoting equally effective but cheaper therapy by directing the

use of the cheapest version of any drug that has passed the

quality standards of the Malaysian Regulator

We adopt the Danish Danish National Health Service model for

physician appeals against directed prescribing:

• Patients could still be prescribed another alternative drug and

have this reimbursed. However, the prescribing physician has

to justify the rationale to the authorities and have the

explanation accepted before other drugs can be reimbursed.

• Otherwise patients are subject to 100% co-payment



Cost/effectiveness

High

<1 x GDP

Moderate

1 <2 x GDP

Poor

>2 x GDP

Clinical

effect

Extremely

effective

Moderate

efficacy

Minimal

efficacy

We hope to agree

MOH funding for

these

Push for generics, biosimilars, price

reductions or cheaper

dose/schedules to bring expensive

treatment inside MOH funding zone

Release value from current programme with

generics, biosimilars, or cheaper

dose/schedules to free-up resource

And reinvest the

savings into

innovative care


reimbursement Guidelines 2015

That we release value from within the current cancer drug budget

to reinvest in innovative cancer therapies

That we adopt the Danish National Health Service model for

promoting equally effective but cheaper therapy by directing the

use of the cheapest version of any drug that has passed the

quality standards of the Malaysian Regulator

We adopt the Danish Danish National Health Service model for

physician appeals against directed prescribing:

• Patients could still be prescribed another alternative drug and

have this reimbursed. However, the prescribing physician has

to justify the rationale to the authorities and have the

explanation accepted before other drugs can be reimbursed.

• Otherwise patients are subject to 100% co-payment

DOI: http://dx.doi.org/10.1007/s11523-011-0196-3

Albert Einstein



the value of generics and biosimilar drugs

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