This presentation provides an overview on the evaluation of biosimilars and extrapolation of indications.

1. Extrapolation of indications for biosimilars
Regulatory perspective
Dr Michael Coory
Director, Prescription Medicines Clinical Unit 5
Medicines Authorisation Branch
Market Authorisation Division, TGA
ARCS Scientific Congress 2015
7 May 2015

2. Regulation of medicines is international
• European Medicines Agency (EMA)
• United States Food and Drug Administration (FDA)
• Health Canada
Extrapolation of indications for biosimilars 1

3. What is a biosimilar?
• Biological medicine that is developed to be ‘similar’ to an existing
biological medicine (the ‘reference medicine’)
• It is not identical to the reference medicine.
– the biological medicine is the process
(“brewed” in living cells; complex processes)
– Biological medicines can never be reproduced as identical molecules
– The concept of identity does not apply
Extrapolation of indications for biosimilars 2

4. What is a biological medicine?
• Medicine produced or extracted from a biological source
Extrapolation of indications for biosimilars 3

5. Not all biosimilars are the same
• Vaccines
• Blood products
• Enzymes
• Hormones
• Immunomodulators
• mAb
Extrapolation of indications for biosimilars 4

6. Biosimilarity is a matter of degree
• Different batches of the originator product
– biosimilars of the version of the product used in the pre-marketing trials
– biosimilars of other batches
– ‘drift’
• Some variation must be accepted for all biological medicines
• The claim is similarity in all important aspects
Extrapolation of indications for biosimilars 5

7. Regulatory balance
Avoid allowing drugs
that are not adequately
tested from coming to
market
Avoid regulatory hurdles
that are unnecessarily
burdensome and do not
protect the public’s health
Extrapolation of indications for biosimilars 6

8. Costs of development
Indicative
Small-molecule
generics
$1–2M 1–3 years
Biosimilars $10–40M 6–9 years
New biological
medicine
$B+ 10+ years
Extrapolation of indications for biosimilars 7

9. CTD Modules
New biological
medicine
3. Quality
4. Nonclinical
5. Clinical
Biosimilar
3. Quality
4. Nonclinical
5. Clinical
• Longer process to
develop the cell line and
manufacturing process
• Takes much longer to
find a cell-line that will
produce a product similar
to the reference product
• Shorter non-clinical and
clinical
• ‘Integrated comparability
exercise’
Extrapolation of indications for biosimilars 8

10. To maintain a regulatory balance
• Avoid unnecessary clinical trials
• Equivalence/non-inferiority
– Need larger sample size that superiority study
– 100’s of patients
• Timely recruitment can be difficult
Extrapolation of indications for biosimilars 9

11. EMEA/CHMP/BMWP/42832/2005
Guideline on similar biological medicinal product …
• In certain cases … can extrapolate indications
• Justification depends on:
– clinical experience
– available literature data
– mechanism of action
– receptors
• Also need to consider safety in subpopulations
Extrapolation of indications for biosimilars 10

12. EMEA/CHMP/BMWP/42832/2005/ Rev.1
Guideline on similar biological medicinal product …
6. Extrapolation of efficacy and safety from one therapeutic
indication to another
EU
July 2015
Australia
Consultation with industry is due to conclude 22 May 2015
Extrapolation of indications for biosimilars 11

13. EMEA/CHMP/BMWP/42832/2005/ Rev.1
• Needs to be scientifically justified
• Considered in light of the totality of data:
– quality
– non-clinical
– clinical
Extrapolation of indications for biosimilars 12

14. EMEA/CHMP/BMWP/42832/2005/ Rev.1
It is expected that the safety and efficacy can be extrapolated:
• when biosimilar comparability has been demonstrated
• by thorough physico-chemical and structural analyses
• as well as by in vitro functional tests
• complemented with clinical data (efficacy and safety and/or PK/PD data)
• in one therapeutic indication.
Extrapolation of indications for biosimilars 13

15. EMEA/CHMP/BMWP/42832/2005/ Rev.1
Additional data are required in certain situations, such as
1. The active substance of the reference product interacts with several receptors
that may have a different impact in the tested and non-tested therapeutic
indications
2. The active substance itself has more than one active site and the sites may
have a different impact in different therapeutic indications
3. The studied therapeutic indication is not relevant for the others in terms of
efficacy or safety, i.e. is not sensitive for differences in all relevant aspects of
efficacy and safety
Extrapolation of indications for biosimilars 14

16. EMEA/CHMP/BMWP/42832/2005/ Rev.1
Immunogenicity is related to multiple factors, including:
• the route of administration
• dosing regimen
• patient-related factors and disease-related factors
(e.g. co-medication, type of disease, immune status).
Thus, immunogenicity could differ among indications. Extrapolation of
immunogenicity from the studied indication/route of administration to other uses of
the reference product should be justified.
Extrapolation of indications for biosimilars 15

17. Summary
• Regulatory framework is evolving
• Not all biosimilars are the same
• Extrapolation: case-by-case
Extrapolation of indications for biosimilars 16