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

Dr Paul Cornes,
Consultant Oncologist,
Bristol Haematology & Oncology Centre
 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
paul.cornes@yahoo.co.uk

 Strive not to be a success,
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
5 cancer
drugs
<1960
+ 2
more
1960s
+ 18
more
1970s
+ 14
more
1980s
+ 24
more
1990s
+ 23
more
2000s
+ 20
more in
only 3
years
2010-13
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
Drugs in
development,
2010
900 drugs in
development
are for cancer
The costly war on cancer. The Economist. 2011 May 26. http://www.economist.com/node/18743951

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
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
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

Money doesn’t always buy life
Life expectancy at birth and health spend
3 fold variation
WHO. The World Health Report 2000

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
>10 fold variation
US Dollars

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
We hope to agree
MOH funding for
Clinical
effect
Extremely
effective
Moderate
efficacy
Minimal
efficacy
these

Cost/effectiveness
High
<1 x GDP
Moderate
1 <2 x GDP
Poor
>2 x GDP
We hope to agree
MOH funding for
Clinical
effect
Extremely
effective
Moderate
efficacy
Minimal
efficacy
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
Richard Sullivan et al –
Lancet Oncology, 2011;12(10):933-980
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.

Classes of treatments to target for cost-effective
care
Richard Sullivan et al –
Lancet Oncology, 2011;12(10):933-980
Ref: Sullivan R et al. Delivering affordable cancer care in high-income countries. Lancet Oncol 2011;12:933

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.
Ten leading causes of
inefficiency
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

Education to promote cost-effective care
“billions of euros are wasted,
say researchers, because
doctors prescribe branded
drugs when a generic
equivalent is just as good”
Wagstaff A. Cancer World 2007 March/April p24-28

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
The more manufacturers make a drug – the lower the price
relative to the original branded pharmaceutical
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

USA – increasing generic use year on year
Generics are now dispensed 94% of
the time where a generic form is
available
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

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
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
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

Generics bring treatments into reimbursement
that might otherwise be unaffordable
$52,983 / QALY
$7,753 / QALY
 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
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
regulatory affairs
immunogenicity and pharmacovigilance
R&D
Pre clinical
Phase 1 clinical
trial
Phase 3 clinical
trial
EMA approval
Phase 4 / PM
surveillance

Current European approved 'biosimilar'
medicines - 2013
 Somatropin - Human Growth Hormone
 Epoetin-alfa & zeta
 Filgrastim
 InflixiMab
2 classes of drug - potentially useful to manage
anaemia and neutropaenia in oncology
1st in class – Biosimilar Monoclonal
 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

Biosimilar medicines
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
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.

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
$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
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
With no loss of
efficacy
With no no serious
or unexpected
adverse drug
reactions
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

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
annual savings from one
drug alone >£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

Savings from biosimilars - London
 Savings from Biosimilar G-CSF switch in London
 G-CSF purchasing cost £3.3 million per year in
2010
£2 million saving from Biosimilar
switch predicted by 2012
– 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

Evidence that biosimilar savings are real
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
Aapro M, Cornes P, Abraham I. J Oncol Pharm Practice 2011 In press

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

Comparative costs associated with estimates of
treatment duration across three tumour types
€620
€1415
€833
€582
€782
€1415
€410
€1415
€551
Biosimilar GCSF
Neupogen®
Neulasta®
Unit dose costs (€)
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
UK G-CSF volume growth
Percent change vs. previous year
2007 2008 2009 2010
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
UK G-CSF volume growth
Percent change vs. previous year
2007 2008 2009 2010
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
Nearly twice as many
patients treated after
biosimilars introduced
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

Biosimilars improve the standard of care
 % of G-CSF as biosimilars vs Neupogen in Europe, Feb 2013
But not all
European Countries
access the benefits
equally
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

Savings drive increased access to treatment
 Savings from Biosimilar G-CSF switch in
Southern Health Care region in Sweden
(population 1.7 million)
fivefold increase in daily G-CSF usage
But still net savings of €2 million
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
Incidence of febrile neutropenia in patients
receiving secondary prophylaxis
20
15
5
0
≥ 7 days of
NEUPOGEN
(Mean = 10.1 days)
10
<7 days of
NEUPOGEN
(Mean = 4.7 days)
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
"... 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,
2008
http://www.youtube.com/watch?v=g
AW56_4gxS8
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

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
"... 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
23_2011_Article_196.pdf
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
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
http://www.ema.europa.eu/docs/en_GB/document_library/Medicine_QA/2009/11/WC500012382.pdf
http://www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/document_listing/document_listing_000318.jsp&mid=WC0b01ac0580281bf0

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

Physicians’ knowledge of biosimilars
remains insufficient:
 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
http://www.bloomberg.com/news/2014-03-18/a-quarter-of-doctors-in-europe-
can-t-define-biosimilars.html
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

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
Editorial. Building a wall against
biosimilars. Nature Biotechnology
2013;31(4):264
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

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
12,039 patients in
58 clinical trials
193 Post Authorisation Adverse event
reports from EU DRA Vigilance
Ebbers HC et al. The safety of switching between therapeutic proteins. Expert Opin Biol Ther 2012;12(11):1473-85

Review of all published data on switching
between originator and biosimilar
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
Ebbers HC et al. The safety of switching between therapeutic proteins. Expert Opin Biol Ther 2012;12(11):1473-85

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
R
a
n
d
o
m
i
s
e
Year 1 Year 2
Infliximab
Originator
Infliximab
Biosimilar
Infliximab
Biosimilar
Infliximab
Biosimilar
Randomise
patients
Switch
Classic Biosimilar trial “switching” trial
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

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
Trial
Arm
1 2 3 4 5 6
Randomise
Chemotherapy cycles

neupogen
Trial
Arm
1 2 3 4 5 6
A EP2006 EP2006 EP2006 EP2006 EP2006 EP2006
2
3
B Original Original Original Original Original Original
Randomise
Chemotherapy cycles
Classic Biosimilar trial

neupogen
Trial
Arm
1 2 3 4 5 6
1 EP2006 EP2006 EP2006 EP2006 EP2006 EP2006
2
3
4 Original Original Original Original Original Original
Randomise
Chemotherapy cycles

Pioneer has closed on the trials
database: Results expected soon!
neupogen
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
Randomise
Chemotherapy cycles
“switching” trial

Cancer isn’t alone in finding a use for biologic
drugs
http://ard.bmj.com/content/72/3/315.extract
http://bmctoday.net/practicaldermatology/2011/05/article.asp?f=what-you-need-to-know-about-biosimilars
http://ndt.oxfordjournals.org/content/21/suppl_5/v4.full

How to promote generic use?
 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)
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

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:c6449
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
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
Number00219. doi: 10.3389/fphar.2014.00219.

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
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
Number00219. doi: 10.3389/fphar.2014.00219.

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.
inefficiency
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

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

Proposal: Malaysian National Cancer
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
Strive not to be a success,

The value of generics and biosimilar drugs

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