fermin ruiz de erenchun | global head biologic strategy team pharmaceuticals...
TRANSCRIPT
Roche Pharma Day 2015
Biosimilar market in context
Fermin Ruiz de Erenchun | Global Head Biologic Strategy Team
Pharmaceuticals Division
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Biosimilars: Ten years in the making
Regulatory environment
Summary
Biosimilars: Ten years in the making
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2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
EU pioneered the biosimilar
concept
– Six products approved, including the first mAb biosimilar (infliximab)
– Uptake did not achieve
saving expectations
WHO leading global efforts; many emerging countries implemented WHO biosimilar guidelines as a reference
US published final biosimilars guideline
– FDA pathway operating, 3 applications pending, one approval
Biosimilar entry timelines delayed (incl. Herceptin & MabThera)
Differential adoption of WHO biosimilar guidelines led to registration of Non-Comparable Biotherapeutic products (NCBs)*, driven by:
– Capacity issues at National
Regulatory Agencies
– Local economic development policies
*For definition and industry position on NCBs please refer to IFPMA Policy Statement:
http://www.ifpma.org/uploads/media/Non-comparable_Biotherapeutic_Products__English__01.pdfr
0.6 6.3
57.0
80 95
119
219
267
317
254
315
377
0
50
100
150
200
250
300
350
400
MAT Jun 2013 MAT Jun 2014 MAT Jun 2015
Sa
les in
CH
Fm
Infliximab
Somatropin
Filgrastim
Epo
Current biosimilar trends
So far, sales have not achieved initial expectations
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MAT 870 CHFm (June 2015) (CAGR 25.5%)
*Excludes US as no biosimilars have been approved in the US so far (Omnitrope was approved under the 505(b) pathway)
IMS Health; MAT=moving annual total
Generics vs biosimilars
Clear divide in uptake; complex market drivers
0%
20%
40%
60%
80%
100%
Year 0 Year 1 Year 2 Year 3 Year 4 Year 5 Year 6
5
Market share
Zyprexa (Eli Lilly)
Diovan (Novartis)
Filgrastim
EPO
Somatropin
Small molecule
Virtually disappear
Payer driven: 7 biosimilars
Efficacy visible immediately
High turnover of patients
Driven by price and patient offering
9 innovators, one biosimilar
Efficacy visible only longer term
No switching
Sources: IMS Biosimilar Dashboard, IMS & Roche analysis 1 Volume market share based on EU5 average; 2 Volume market share based on average of France & Germany EPO; 3 Data based on % remaining sales in EU
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1
2
3
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Despite 10 years of experience in the EU,
uptake of biosimilars differs across countries
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Bio
sim
ila
r p
en
etr
ati
on
of
ac
ce
ssib
le m
ark
et
Reference: Assessing biosimilar uptake and competition in European markets. Report by the IMS Institute for Healthcare Informatics.
HGH=human growth hormone; EPO=Erythropoietin; G-CSF=Granulocyte-colony stimulating factor
Anti-TNF market is not a good analogue for
oncology
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Anti TNF
Other
biologics
IV Anti-TNF
SC
Anti-TNF
Biological
products used
to treat RA, IDB
& Psoriasis
Infliximab biosimilar could expand beyond it’s accessible market and obtain market
share from Enbrel® and Humira®
Remicade®
Biosimilar accessible market
Small molecules and biologics
Not all the same
• Small molecule policies allow substituting patients only the price counts
• For biologics, European Medicine Agency (EMA) does not provide
guidance on interchangeability and substitution
• Most countries in Europe have specific policies in place to distinguish
between small molecule and biologic medicines
– Biologics must be prescribed by brand name
– Laws against substitution
– Switching remains a physician’s choice
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Payer environment is one of multiple drivers for
biosimilar uptake
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Drivers?
Payer environment
Therapeutic area
Innovation and change in
SoC
Physician’s support
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Biosimilars: Ten years in the making
Regulatory environment
Summary
Biosimilar pathways
in place
Biosimilar pathways
under development
2010 2015
Establishment of biosimilar guidelines has
increased driven by WHO efforts
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Requirements and study designs are different
for biosimilars vs innovator products
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Aspects of
development Biosimilar Innovator product
Patient population Sensitive and homogeneous
(patients are models)
Any
Clinical design Comparative versus innovator,
normally equivalence
Superiority vs standard of care
(SoC*)
Study endpoints Sensitive, clinically validated PD
markers
Clinical outcomes data or
accepted/established
surrogates (e.g. OS and PFS)
Safety Similar safety profile to
innovator; no new findings
Acceptable benefit/risk profile
versus SoC*
Immunogenicity Similar immunogenicity profile to
innovator
Acceptable risk/benefit profile
versus SoC*
Extrapolation Possible if justified Not allowed
* In some cases SoC may not exist
How should extrapolation risk be managed?
The regulator’s perspective
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Analytical
Non-clinical
Clinical
How should extrapolation risk be managed?
The physicians’ perspective
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Analytical
Non-clinical
Clinical
Analytical
Clinical
Non-clinical
I would like to
see a phase III
trial for each
indication
What is the right patient population to establish
clinical similarity to Herceptin?
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Topic Metastatic population
(advanced BC)
Neoadjuvant/Adjuvant population
(early BC)
PK Affected by patient`s status & tumor
burden
Homogeneous population can be
selected
PD Clinically validated PD marker not available
Clinical
efficacy/safety • Difficult to select homogeneous group
• Need to control and stratify for multiple
factors (e.g. prior use of chemotherapy,
performance status…)
• Population with heterogeneous
characteristics affecting final clinical
outcome
Populations less likely to be confounded by
baseline characteristics and external
factors
Immunogenicity Immune system affected by performance
status and concomitant chemotherapies
received
Immune system impaired during
chemotherapy cycles, but likely to
recover to normal status thereafter
mBC Phase III Start
Date
Regulatory
Filing
eBC Phase III Start
Date
Celltrion Q2 2010 Q1 2014
Mylan Q4 2012
Pfizer Q4 2013 Q2 2014
Samsung Q2 2014
Amgen Q4 2013
Pfizer
Samsung
2011 2012 2013 2014 2010
mBC
eBC
Initiation of
clinical trial(s)
Celltrion Mylan Pfizer
Celltrion
Amgen
The regulatory thinking is evolving
The Herceptin case
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Biosimilars: Ten years in the making
Regulatory environment
Summary
Generics, biosimilars: Not all the same
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• Small molecules: Policies allow fast penetration of generics
• Biosimilars: Countries in Europe have specific policies in place to distinguish
between small molecule and biologic medicines
– Biologics must be prescribed by brand name, laws against automatic
substitution, switching remains a physician’s choice, EMA - no guidance
on interchangeability
– After 10 years of experience in the EU, uptake of biosimilars differ heavily
across countries
• Regulatory environment: Still evolving with authorities in the process of finally
establishing frameworks; case by case decisions likely