Transcript Document

Second Annual Biotech Supply Chain Academy
Keynote Address
Regulatory Influences in
Biogenerics-the Next
Horizon
Gillian R. Woollett, M.A., D.Phil.
Chief Scientist
Engel & Novitt, LLP
The Law Firm That Knows Its Science
October 19, 2009, San Francisco, CA
The material and viewpoints set forth in this slide deck
and conveyed during this presentation are presented by the author
in her capacity as Chief Scientist of Engel & Novitt, LLP.
They do not represent and do not purport to represent the views of the law firm
or any current or former-client of the firm, and should not be construed as such.
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OUTLINE
 The premise of competition when patents expire
 Biotech products and the biotech pipeline – a






whole lot more are on the way…
Minimal terminology for the biologics debate
The current US regulatory framework
Biologics - the need for them is global, but can
they be made for a global market?
Biologics business models and lessons from the EU
biosimilars experience
Current legislative efforts to create a new
regulatory pathway
Opportunities and Conclusions
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The Traditional Incentives for Innovation
Incentives created by competition create new medicines & increase access
Generics offer
high quality drugs for
established treatments
affordable costs
and thereby free up
healthcare funds for new
innovative drugs
Patents Expire
Innovative drugs offer:
Net Progress
Radical New
Therapies and
Iterative
Improvements
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Improved treatment
Less side effects
New therapeutic options
and thereby replace
older/less effective
medications
Obsolescence
3
The Context for ALL Biologics
The 200 year history of biologics is the basis for their future:
 Started with the very complicated – smallpox vaccine – and the
decisions were empirical, and the studies “unethical”
 The biotech industry is much younger (first recombinant insulin
1982), and the original biotech products were “biosimilars” essentially biotech was a means of manufacturing previously
approved naturally-sourced products. Now we can do way more
as in Never-before-seen-in-nature products…
 FOBs are not just biosimilars, but also bioidenticals, second-
generation products, biobetters, and bio-I-just-don’t-knows
 Biobetters can be clinically-better, but also perhaps safer, more
stable, more reliably manufactured and cheaper, or all of the
above
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The Economic Issues for Biologics
Matter NOW
 Healthcare costs are high and increasing - all economies are under
pressure, but access is life/death
 Individual biopharmaceuticals are more expensive than drugs on a
per-patient basis, so prices have become conspicuous - attracting
political and media attention.
 Medicines are a critical part of healthcare worldwide, but there is
considerable price and product disparity, yet the companies and
the patients are the same
 Biologics are, or are coming, off-patent
 Arguments for free-market pricing of drugs evoke an expectation
of competition in the marketplace at the conclusion of patent
terms
 The opportunities from multiple sponsors are increasingly apparent
to all stakeholders; conversely their lack is a liability to biopharma
and patients
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BIOTECHNOLOGY
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Number of Products in Clinical Trials
Biotech Medicines in Development
700
633
600
500
418
400
284
300
143
200
100
369 371
324
Represents
pipeline for
future Brand
products and
then,
subsequently,
for
biosimilars
81
0
1988 1993 1996 2000 2002 2004 2006 2008
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Source: PhRMA Biotech Medicines in Development Surveys 7
The
majority of
Medicines
in clinical
trials for
the US may
now be
biotech
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http://www.phrma.org/images/110308%20biotech%202008.pdf
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PhRMA Biotech Medicines in Development
2008
Total
Biotech
Medicines in
clinical trials
for the US
633
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http://www.phrma.org/images/110308%20biotech%202008.pdf
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Current US Regulatory Pathways
STATUTE
APPLICATION
U.S. FOOD DRUG
& COSMETIC ACT
NEW DRUG
APPLICATION (NDA)
AND 505(B)(2) NDA
ABBREVIATED NDA
(ANDA) = GENERIC DRUG
U.S PUBLIC
HEALTH SERVICE
ACT
BIOLOGIC LICENSE
APPLICATION (BLA)
EXPEDITED
BLA
Derived from a Presentation By Keith Webber, Deputy Director, OPS, FDA. 25Sep07 GWU “Biosimilar 2007”
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Terminology has been distracting…
 Biologic – is a prophylactic, in vivo diagnostic, or therapeutic
substance that is made in a living system, and that, generally,
has a large and complex molecular structure
 Follow-on Biologic (FOB) – a subsequent version of a biologic,
independently developed and approved, but that shares the same
mechanism of action as a previously approved product (includes
so-called EU Biosimilars, plus some second generation biologics)
 Second-generation biologic - subsequent versions of biologics that
are independently developed and approved, share the same
mechanism of action as a previously approved product but are
explicitly different in some manner, e.g. inhaled. Sometimes called
“evergreened”.
 Biogeneric, or Generic Biologic Drugs – should only be applied to
ANDAs for biologic drugs approved by FD&C Act. ANDAs are
interchangeable with their reference product
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And please remember, while there may
be a debate on naming…
…THE NAME DOES
NOT CHANGE THE
CONTENTS OF
THE TUBE
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So how do you tell what is in the tube…
…with
DATA
And hence the issue for any biologic sponsor is what data, to
demonstrate what, and to whom, at what price to get what
market…
Answer: data to show safety, purity and potency or a
relationship to a reference product (with known safety, purity
and potency) at the structural, functional, and clinical levels
to the regulators
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Where are we with biosimilars today?

Generally accepted that the science is sufficient for some/most
biosimilars today

Europe, Australia, Canada, Japan have biosimilars and
competition is beginning

No Enacted US legislation but bills in play (albeit drowned in
the larger health care reform debate)

Recognition of need for biologics competition in US as patents
expire, but aggressive defense by some Brands

Huge confusion on the role of reimbursement, and need for
interchangeability to gain savings and access

Health care reform an Administration priority, and biosimilars
seen to have potential to increase access and save money

Global issues
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The Biosimilars Story of Europe – a
Timeline
 17Dec03 European Parliament “Future Medicines Legislation” (also
called “Pharma Review Package”)
 31Mar04 Directive 2004/27/EC (also known as Directive
2001/83/EC as amended) and Regulation 726/2004. Came into
effect 20Nov05
 EMEA published general guidelines on biosimilars, as well as
“class”-specific ones, but accepts and reviews applications
concurrently
 Approvals: April 06 First biosimilar approval was Omnitrope
(somatropin); August 07 First glycosylated protein approved as a
biosimilar, Binocrit (Epoetin alfa); March 09 EMEA Guideline on
LMWH – first for a naturally-sourced biosimilar
 EMEA meeting on Biosimilar Monoclonal Antibodies Jul09
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Selected Therapeutic Biologics by Product Class
Average
~150Kd
Average
<50Kd
European Biosimilars are based on wellestablished regulatory standards
 1996 US Guidance on Comparability for Manufacturing Changes for
drugs and biologics developed by FDA and Pharma
 Early 2000’s ICH Q5E Comparability standards adopted by EU US
and Japan – HIGHLY SIMILAR
 EU Biosimilars based on similarity and guidelines developed, but
MEANWHILE biosimilars were developed and approved.
 No central EU regulatory designation of interchangeability, up to
the health authorities in each country
 Review and approval not coupled to patents
 Innovator exclusivity 8+2+1 for all medicines (drugs and biologics
are the same)
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The Established Definition of Comparability
(EU, US, Japan)
ICH HARMONISED TRIPARTITE GUIDELINE
COMPARABILITY OF BIOTECHNOLOGICAL/BIOLOGICAL
PRODUCTS SUBJECT TO CHANGES IN THEIR
MANUFACTURING PROCESS
Q5E
COMPARABLE:
A conclusion that products have highly similar quality
attributes before and after manufacturing process
changes and that no adverse impact on the safety or
efficacy, including immunogenicity, of the drug product
occurred. This conclusion can be based on an analysis of
product quality attributes. In some cases, nonclinical or
clinical data might contribute to the conclusion.
Federal Register, Vol. 70, No. 125, June 30, 2005, pages 37861-37862
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Clinical
safety & efficacy
PK/PD
Preclinical
Biological
characterization
Product
development
Physicochemical
characterization
Complete product
and process
development
Define
target
Confirm comparability
with reference product
The Comparability Exercise is fundamental to the
Development of an EU Biosimilar Product
Define and
characterize
reference product
The comparability/similarity with the reference
product must be demonstrated at all levels of
product development:
 Analytical comparability - physicochemical
 ESTABLISHING SIMILARITY
 Functional Comparability in assays, and
shown by animal studies
 CONFIRMING SIMILARITY
 Clinical Comparability shown in Phase I and
III studies
A biosimilar product is designed to meet the
criteria of the reference product with regards to
quality, safety and efficacy.
This rigorous comparability exercise qualifies
Biosimilars for therapeutic interchange
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Derived from a Presentation By Ingrid Schwarzenberger, Sandoz
23Sep08 GWU “Biosimilar 2008”
19
Presented
by The
Thomas
Moore
at Sanford
ENGEL & NOVITT,
LLP
Law Firm
That Knows
its ScienceBernstein Biosimilars Conference, 3Dec09
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The Safety and Efficacy of EU Biosimilars
Nicolas Rossignol, then Administrator of the EC’s
pharmaceuticals on questions of safety for EU biosimilars:
"I don't judge case by case, but I have a message:
we have promoted and developed with the European
Medicines Agency a special biosimilars framework.
So we are confident that if a product meets all the
requirements and gets a marketing authorisation
from the commission, it means that the product is
as safe and effective as any other product
authorized by the commission"
SCRIP World Pharmaceutical News 24 April 2008, reporting on EGA
Meeting, London
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The EU Biosimilars approved to date
EU Biosimilar
INN
Reference Product
Auth./Pos. Op. Date
Omnitrope
Somatropin
Genotropin
12 April 2006
Somatropin
Humatrope
epoetin alfa
Eprex/Erypo
epoetin alfa
Eprex/Erypo
epoetin alfa
Eprex/Erypo
epoetin zeta
Eprex/Erypo
epoetin zeta
Eprex/Erypo
filgrastim
Neupogen
filgrastim
Neupogen
filgrastim
Neupogen
filgrastim
Neupogen
Filgrastim
Neupogen
filgrastim
Neupogen
(Sandoz)
Valtropin
(Biopartners)
Binocrit
(Sandoz)
Epoetin alfa Hexal
(Hexal)
Abseamed
(Medice)
Retacrit
(Hospira)
Silapo
(Stada)
Biograstim
(CT Arzneimittel GmbH)
Filgrastim Ratiopharm
(ratiopharm GmbH)
Ratiograstim
(ratiopharm GmbH)
Tevagrastim
(Teva Generics GmbH)
Zarzio
(Sandoz)
Filgrastim Hexal
(Hexal)
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(Pfizer)
(Eli Lilly)
(Janssen-Cilag)
(Janssen-Cilag)
(Janssen-Cilag)
(Janssen-Cilag)
(Janssen-Cilag)
(Amgen)
(Amgen)
(Amgen)
(Amgen)
(Amgen)
(Amgen)
24 April 2006
28 August 2007
28 August 2007
28 August 2007
18 December 2007
18 December 2007
16 September 2008/
24 July & 21 Feb 2008
16 September 2008 /
24 July & 21 Feb 2008
16 September 2008 /
24 July & 21 Feb 2008
With
approval
sponsors
gain
access in
all 27
countries
of the EU,
but
reimburse
-ment
systems
still vary
by
country
16 September 2008/
24 July & 21 Feb 2008
13 February 2009/20 November 2008
13 February 2009/20 November 2008
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22
FDA Precedents for Everything?
Naturallysourced
products
Naturallysourced
products
Recombinant
products
Brand Name
Generic Name
Regulatory
Pathway
Date of FDA
approval
Sponsor
Repronex
menotropins
ANDA
10-Jan-97
Lederle/
Ferring
Repronex
menotropins
505(b)(2)
27-Aug-99
Ferring
Vitrase
hyaluronidase
505(b)(2)
5-May-04
Ista Pharms
Amphadase
hyaluronidase
505(b)(2)
26-Oct-04
Hydase
hyaluronidase
505(b)(2)
25-Oct-05
Glucagen
glucagon
hydrochloride
recombinant
calcitonin salmon
recombinant
505(b)(2)
22-Jun-98
505(b)(2)
12-Aug-05
hyaluronidase
recombinant
human
somatropin
505(b)(2)
2-Dec-05
Halozyme
Wydase (Baxter, 22Mar-50 )
505(b)(2)
30-May-06
Sandoz/
Novartis
Genotropin (Pharmacia
and Upjohn, 24-Aug-95)
Fortical
Hylenex
Omnitrope
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Reference product
(sponsor, date of
original approval)
Pergonal (Serono, 1969)
Pergonal (Serono, 1969)
Wydase (Baxter, 22Mar-1950 )
Amphastar
Wydase (Baxter, 22Mar-50 )
Primapharm
Wydase (Baxter, 22Mar-50 )
Novo Nordisk Glucagon (Lilly, 14-Nov60)
Upsher Smith Miacalcin (Novartis, 17Aug-95)
23
But, for all biologics suppliers…
 Regulatory requirements have increased as the collective ability to
do “more science” has increased - sameness has become pursuing
everything with every technique every time to show the absence
of a difference…
 Reference standards are not routinely available. No API
commercial model for biologics
 Comparability has become increasingly difficult, even for
innovators with their own products, e.g. when getting new facilities
on line, resulting in shortages. This drives pressures for more
suppliers. Quality matters.
 Alternative sources/products are needed, and also incented by the
expanding markets (range of products, and more patients needing
access), and manufacturing can be more efficient…
 Products in one market drive demands in others – global needs
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Innovator comparability complicates the
story
 AVONEX (Interferon Beta 1A) approved in 1996 based on
comparability and without clinical studies on final material
 MYOZYME (alglucosidase alfa) for the treatment of late onset
Pompe disease. FDA decides material made at different scales are
different products (Oct08)
 CEREZYME (Imiglucerase) manufacturing shortages due to viral
contamination such that different products subject to expanded
access studies (Protalix – Glucocerebrosidase) or switching
(Zavesca - miglustat)
FDA authority to use comparability is clear, but their caution
continues to be evident. Hence, it has become a very high
regulatory standard, and innovators inability to achieve it for their
own products suggest that biosimilars sponsors will have challenges
too.
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Biosimilars can enable Regulatory
Progress for all Biologics
 The PHS Act (1903) requires a demonstration of safety, purity and
potency. New legislation can enable, not impede, the
accommodation of scientific progress into the regulatory
framework – a win:win for all sponsors.
 The goal of regulations for ANY biologic should be only to require
actionable data, i.e. ONLY, but ALL, necessary data on which to
make appropriate decisions. Regulations need to evolve with the
science if innovator products are to be licensed, and the promise of
biotech fulfilled.
 Biosimilars are self-evidently possible, and FDA needs to the
authority to evaluate them and when appropriate designate them
as interchangeable. Only FDA will see the data and the licensure
has to be data-driven.
 The FDA already has a >12 year old “sameness standard” for
biologics and drugs called comparability
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Progress in science and regulations is a
continuum…
…and should be global
Bio-manufacturingtechnology
•Process Analytical
Technology
•MOA
•Quality by Design
Analytics
•Improved
technology
•Orthogonal
methods &
data
integration
Progress in ALL or
ANY give greater
certainty to the
development of:
Pre-clinical
•Better disease
models
•Comparative
immungenicity
•Better predictive
safety models
Clinical
•Critical Path
•Adaptive clinical
trials design
•Post-marketing
studies
•More predictable
outcomes
•Validation of
biomarkers as
surrogate
endpoints
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• First generation
biologics
• Follow-on
biologics
• Including second
generation
Note: Biologic can be manufactured
using biotechnology, synthetic
chemistry or using natural sources;
some have been made with all three
27
So why are we having these discussions
about biosimilars, and why now?
 BIOTECH IS A STORY OF SUCCESS Innovator biologics work
and patents are expiring. Consumers want more of them, both as
innovator products, and as cheaper versions of old products.
Access matters and is an unmet medical need.
 ECONOMIC PRESSURES ARE ADDING TO THE NEED FOR A
SOLUTION ASAP Patents ending are visible, as are EU successes
with biosimilars, but cost is the biggest issue by far (both
individual and collective).
 WE NEED COMPETITION FOR BIOLOGICS, AS WELL AS
DRUGS A lot can be learnt from the successes and failures of
generic drugs, but we need a process to be appropriate for
biologics. That requires legislation and the details will determine
the savings.
 THE ISSUES ARE GLOBAL
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Patient access to Rx depends on market
access for Rx
GLOBAL
ACCESS
Patients are everywhere
(albeit Dx and healthcare
infrastructure vary)
REGIONAL/NATIONAL
Healthcare systems vary
(affects reimbursements
and ROI, 1y & 2y markets)
IP varies, and getting a
Market access is
little better harmonized,
determined by but barely (certain global
regulatory
approval, free-trade norms are
Companies develop
and
viability by emerging but limited)
manufacture formarket
the
leading markets, ideally
reimbursement
global standards
COMPETITION REQUIRES
Regulations are regional
(inconsistent requirements
MARKET ACCESS &
with some
lead to requirements for
FREEDOM TO PRICE harmonization for
different products)
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drugs, and innovator
biologics (cost of getting
to market less if can use a
single data set)
29
BIOLOGICS/SIMILARS – the need for them is
global, but can they be made for a global market?
US
Legislative
debate
0.31
Europe
Pathway in
place
THE LEADER
0.50
ICH plus others
(1st World)
Japan
Guidance
Final
0.13
WHO
Biosimilar Guidelines
near final
World Population
Total 6.7
Canada
Guidance
Final
0.03
Australia
Using EU
approach
0.02
Brazil
0.19
Russia
0.14
India
1.14
Largely
Supporting
WHO
Guideline
Initiative
China
1.13
BRIC plus others
(2nd World)
ROW (Largely 3rd World)
Largely lack health care infrastructure for complex biologics
WHO less relevant, but will recognize those standards
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Top Approved and Marketed Biologics
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http://www.ftc.gov/bc/workshops/hcbio/docs/fob/rgal.pdf
31
Current US Regulatory Pathways
STATUTE
APPLICATION
U.S. FOOD DRUG
& COSMETIC ACT
NEW DRUG
APPLICATION (NDA)
AND 505(B)(2) NDA
ABBREVIATED NDA
(ANDA) = GENERIC DRUG
U.S PUBLIC
HEALTH SERVICE
ACT
BIOLOGIC LICENSE
APPLICATION (BLA)
EXPEDITED
BLA
Derived from a Presentation By Keith Webber, Deputy Director, OPS, FDA. 25Sep07 GWU “Biosimilar 2007”
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Licensure of Biologics in the US today:
The only pathway is the “Full BLA”
Raw
Material A
Process B
As long as A and B stay the same,
Raw
Material A’
C’
C
Product C
can be sold without more clinical trials
Process B’
Product C’
can be made and licensed today.
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Interchangeability versus Substitutability
SMALL MOLECULE DRUGS
BIOLOGICS
Responsibility of regulators (EMEA
or FDA)
Responsibility of regulators
(EMEA or FDA)
Interchangeability = Therapeutic
Equivalence (based on
Pharmaceutical equivalence plus
Bioequivalence)
Interchangeability =
Comparability (based on
highly similar at structural,
functional, and clinical levels)
Responsibility of health authorities
(Countries or States)
Responsibility of health
authorities (Countries or States)
Substitutability
Substitutability
DO PAYORS NEED THE SUBSTITUTABILITY MODEL OF
GENERIC DRUGS TO GET REAL SAVINGS?
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The US is falling behind…
 European biosimilars are succeeding – 13 marketing
authorizations, increasing visibility and no evidence of
quality, safety or efficacy problems
 The US is the largest biotech market – patents are expiring;
the science is universal; 8 FD&C Act follow-ons to biologic
drugs have been approved as 505(b)(2)s, one ANDA and
two in the wings
 Economic pressures have increased as biotech products
have succeeded – free-market pricing for Rx in the US
cannot expect to continue without competition becoming
evident in the biologics market
 Health care reform in the works – maybe. Biosimilars bills
are included in both US Senate and US House
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Biologics Patent Expiration Estimates
Highlights important of availability of US pathway from date of
enactment
Now
Summary of Estimated Biosimilars Savings
Source
Entire US Population
Entire US population,
but reported Federal
Government savings
Medicare Part B
beneficiaries
Entire U.S. Population
Rolling 10-year period
2008-2017, with no
savings 2007-2012
“next ten years” beginning
with pathway available in
2007
“over the next 10 to 20
years”
Therapies
Evaluated
Erythropoietin, Interferons
for Multiple Sclerosis,
Growth Hormone for growth
deficiency, Insulin for
diabetes
Non-specific therapies.
(Erythropoietin
excluded almost
entirely due to timeline
and gradual market
movement)
All PHS Act regulated
biologics within the top 200
HCPCs that are currently
reimbursed by Medicare
Part B
Generic versions of the top
12 categories of biologic
treatments with patent
protections that have
expired or are due to expire
in the near future
Assumptions
Product specific analysis to
calculate movable market
share. Substitution rates of
83.4% (directly substitutable)
and 49% (therapeutically
substitutable). 25% discount
on biogeneric products.
Assumes 10% of
biologic spend goes off
patent per year. Market
penetration reaches
60% over 3-year period.
Large revenue products
reach discounts of 30%,
medium revenue
products achieve 10%
discount.
Assumes only a single
competitor to each
already-approved biologic
when it goes off patent (and
that all patents are valid);
that the savings will begin
at 15% rising to 30% over
10 years
Assumes that a biogeneric
pathway is approved in
2008 and those products
already off patent could be
approved by 2010.
Assumes rapid introduction
of biogenerics following
patent expirations of
original products. Price
discount of 25-35% over a
10 and 20 yr period.
Conclusion
$71 Billion savings
opportunity in ten years
following approval of generic
biotech products.
Federal Government
can save $3.6 Billion
over ten years
Medicare Part B can save
$14 Billion over next 10
years.
$67 billion to $108 billion
over first 10 yrs and $236
billion to $378 billion over
20 yrs
Population
Timeline
Government Projections for Biosimilars Savings
Source
CBO-1
CBO-2
OMB
CBO-3
Entire US Population, but reported Entire US population, but reported
Federal Government savings
Federal Government savings with and
without Medicare Coding Reform
Entire US Population, but Entire US Population, but
reported Federal
reported Federal
Government savings
Government savings (CBO
Score of Pres. Budget)
10-year period (2009-2018)
10-year period (2010-2019)
10-year period (2010-19) 10-year period (2010-19)
Therapies
Evaluated
Non-specific therapies. Subset of
biologics, that make up roughly
three-quarters of the current
market, that might face
competition by Follow-On
Biologics over the next 10 years
Non-specific therapies. Subset of
biologics, that make up roughly threequarters of the current market, that
might face competition by Follow-On
Biologics over the next 10 years
None identified.
None identified.
Assumption
Assumes S.1695 will be enacted
near start FY 2009 & for
interchangeability with 1 yr of
market exclusivity to the 1st
interchangeable FOB, 12 yrs of
exclusivity to the innovator, and
accounts for the possibility of
“evergreening”. Assumes 35%
market share for FOB and price
discount of 40 % by 4th year of
competition.
Same assumptions as CBO-1 but with
the additional assumption that Medicare
Part B would be modified to place the
follow-on biologic in the same billing
code as the reference product.
Assumes a period of
innovator exclusivity
“generally consistent
with” Hatch-Waxman
and that brands would
be prohibited from
“evergreening”.
Assumes a period of
innovator exclusivity
“generally consistent with”
Hatch-Waxman and that
brands would be prohibited
from “evergreening”.
Conclusion
Federal Government would save
$6.6 Billion over 10 years. Figure
includes revenue changes.
With no coding reform the total savings
to Federal Government on Medicare and
Medicaid would be $9.2 Billion; with the
modification savings would total $12
Billion over 10 years. Figures include
revenue changes.
Federal Government can
save $9.24 Billion over
10 years. It is unclear
whether this figure
includes revenue
changes.
Federal Government can
save $13 Billion over 10
years. Figure includes
changes in revenue.
Population
Timeline
The Payor Role in the utilization of
biosimilars is not yet clear
 An FDA designation of interchangeability can give options for
automatic substitution with the reference product – the “Generic
Drug Model”
 The absence of an interchangeability designation may give greater
or fewer choices for payors, and this will depend on the
reimbursement infrastructure. Options may include:
– Co-pays incentives for patients (tiering)
– Prior authorization for physicians
– Step Therapy and/or switching (happens between payors, but
less likely within)
 De Facto therapeutic substitution may give the greatest potential
for savings to payors and patients
 The role of Government payors will be very influential
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MedPAC recommendations to Congress
(June2009)
 Absent a free-market solution, alternative approaches will be
considered, and they may be difficult for biopharma.
 MedPAC examined three strategies to pay for biologics under Parts
B and D that “by considering information about a drug’s clinical
effectiveness, have the potential to improved the value of Medicare
spending on drugs”:
 Reference Pricing: Set a drug’s payment rate no higher than
the cost of currently available treatments unless evidence
shows the drug improves beneficiaries outcomes
 Payment for results: Link a drug’s payment to beneficiaries
outcome through risk-sharing agreements with manufacturers
 Bundling: Create payment bundles for groups of clinically
associated products and services
 Thus it would appear to be in biopharma’s interest to find a fair
and sustainable solution.
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So what could legislation for the US
include in order to increase competition…
 Delegate authority to FDA to approve biologics that reference a
previously approved PHS Act biologic (data will always be product
specific, and sponsor must show safety, purity and potency). To
maximize competition pathway must be:
– Immediately available
– Apply consistent regulatory standards
– Allow for an interchangeability designations
– Flexible enough to absorb scientific developments
The PHS Act is a paragraph, and works for innovator products, the
ones we know the least about at time of initial approval something equally simple will do for biosimilars
 Respect IP rights of innovators and biosimilar sponsors, plus a fair
exclusivity incentive for innovator products.
 Support global consistency in regulatory requirements, such that a
global market access to biosimilars is possible too
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US Legislation - Overview
• Two Biosimilar Bills are in currently in play in 111th Congress:
• House Energy & Commerce Committee adopted “Licensure
Pathway for Biosimilar Biological Products”
• Senate H.E.L.P. Committee adopted “Biologics Price
Competition and Innovation Act of 2009”
• Both now part of Health Care Reform and to a great extent
dependent on how that develops over the next few months
• Neither have gone to the floor of their respective houses, and
amendments are expected.
• The disparate elements in the two bill will need to be reconciled at
Conference:
• Regulatory Pathways– same
• Exclusivity – similar
• Patent provisions – different
• Even if overall health care reform fails, biosimilars legislation may
become a “lifeboat”
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Senate Biosimilars Bill
•
•
•
•
•
•
•
Two-Step regulatory pathway based on “highly similar”
standard (identical to House)
• Biosimilars - analytics, preclinical, clinical (any of which
can be waived by FDA), extrapolation between indications;
• plus switching studies for interchangeability designation
No blocking guidances or regulations as part of pathway
REMS required
Same generic name (INN) possible
12 year innovator exclusivity (and 180 notification prior to
marketing biosimilar); 1 year for first interchangeable
biosimilar
Complex compulsory patent exchange provisions which put
patents at risk early, amends Title 35
No requirement for regulations to be promulgated
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House Biosimilars Bill
•
•
•
•
•
•
Two-Step regulatory pathway based on “highly similar” standard
(identical to Senate)
• Biosimilars - analytics, preclinical, clinical (any of which can
be waived by FDA), extrapolation between indications;
• plus switching studies for interchangeability designation
No blocking guidances or regulations as part of pathway
REMS required
Requires unique name, but same generic name (INN) possible
12 year innovator exclusivity, plus possibility of 6 month
pediatric extension; 1 year for first interchangeable biosimilar
Complex compulsory patent exchange provisions which put
patents at risk early, new regulations required, does not amend
Title 35
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FDA Implementation - Expectations
•
•
•
•
Will depend on the details in the final legislation
Hope/expect:
• Pathway implemented immediately (products already in
queue - Woodcock testimony Mar07)
• FDA adequately resourced through user fees
• No requirement for new FDA regulations for pathway to be
available
• Guidances will be developed, as in Europe, concurrently with
the biosimilars being reviewed and approved
Patent litigation could continue as today for biotech, i.e.
independently of FDA review and approval, but current
proposals have it linked such that FDA completes it review, but
waits for the outcome of litigation before issuing the biosimilar
license. As such patents are at risk early. However, no Orange
Book for biologics.
Full BLAs, including for second generation products, continue
with patent litigation as today – unencumbered
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Fundamental questions for any biologic
sponsor - what data, what label, what market?
 Are the regulatory standards for all biologics to be
consistent, namely safety, purity and potency, and are
separate products evaluatable using comparability (ICH,
basis for EU & WHO)?
 Are regulatory authorities to be allowed to designate a FOB
and its reference as interchangeable or will payors decide
individually, absent data and according to their own rules?
 Is the US to get a new pathway – what is it and when is it
usable? Is FDA approval to be linked to the patent system?
 Is competition in the market going to occur, and be seen to
occur? Or is “sameness” going to be a barrier…
 Are the rules enabling access to FOBs going to be consistent
globally?
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Second-generation products, biobetters,
and bio-I-just-don’t-knows
 If it costs more to be biosimilar than to do a “full BLA”, why not be
better but use the advantages of:
– An RLD that has already defined the market value
– Lower failure rate as have a model product
– Studies can be focused, and manufacturing efficient
– Tweaks can be market-based too, e.g. devices, stability
– Not constrained by reverse engineering limitations
– Get your own 12 year exclusivity
 Avoids innovator exclusivity should it be granted in US legislation
(albeit patents still apply – same as today)
 We all learn from prior knowledge, so biobetter can be just not-
shown-to-be-the-same
 Biobetters can be developed for a global market
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Opportunities and Conclusions
 We can learn from generic drugs, but we do not repeat the






mistakes – no need to reinvent the patent morass
All stakeholders understanding their own interests, and engaging
to generate an expedited pathway to enable/increase competition
and access will be a collective win:win. Poles are not helpful.
Quality will always matter, especially in the Post-Eprex and PostVioxx world, and that affects the whole supply chain
Realistic expectations of biologics, as well as drugs, such that the
new products can reach patients and drive the upward cycle of
innovation, access and health matters. That means new biologic
approvals too
Global consistency in regulatory requirements key – lessons from
Europe and beyond are useful
Reimbursement models must recognize biosimilars in a manner
that fosters legitimate competition, not therapeutic substitution
Result can be creation of a regulatory pathway for FOBs in the US,
that enables competition in the biologics market when patents
expire
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Thank You!
Gillian R. Woollett, M.A., D.Phil.
Chief scientist
Engel & Novitt, LLP
The Law Firm That Knows Its Science
www.engelnovitt.com
202.207.3307
[email protected]
The material and viewpoints set forth in this slide deck
and conveyed during this presentation are presented by the author
in her capacity as Chief Scientist of Engel & Novitt, LLP.
They do not represent and do not purport to represent the views of the law firm
or any current or former-client of the firm, and should not be construed as such.
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