aippi pharma session 2 biosimilars: similar but...

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AIPPI Pharma Session 2Biosimilars: Similar but different?

Moderator: Dominic Adair, Bristows

Panellists: Bryan Zielinski, Pfizer

Fritz Reiter, Sandoz

Mei-Hsin Wang, National Yunlin University of Science and Technology

Milan, 19 September 2016

The views expressed by the panellists in this session are their personal views only

and should not be attributed to their organisations. The information provided should

not be relied upon for business purposes or taken to constitute legal advice.

Disclaimer

AIPPI Pharma Session 2: Biosimilars

2

Bryan Zielinski

Vice President,

Assistant General

Counsel

Pfizer Inc.

Dominic Adair

Partner

Bristows LLP

Fritz Reiter

Regulatory CMC

Team Leader

Sandoz GmbH

Mei-Hsin Wang

Chemistry and Law

Professor

National Yunlin

University of Science

and Technology

1. Introduction and background

2. Regulatory issues

3. Patent issues

4. Anti-trust issues

Agenda

3


4

Introduction and background

Background

5

• Biosimilars are not generics

• Chemical small molecules vs biologic products

- Size

- Complexity

- Variability

- Cost

- Time to market

- Safety profile

- Size of treatment population

• Impacts upon

- Regulatory hurdles

- Commercial strategy

- Number of competitors

- Attitude to risk

- Litigation strategy

• Global demand increasing

VALUE (USD MILLIONS) OF GLOBAL BIOSIMILARS MARKET

(Source: BCC Research in Genetic Engineering & Biotechnology News)


BiopharmaceuticalsBusiness Use Only6

Challenges for healthcare systems

Source: shown by Julia Pike at ACI’s 7th Annual Summit on Biosimilars, NYC June 2016



Impact of Biosimilars on healthcare




Biosimilar market expectations



9

Regulatory issues

Approval of biosimilar products

10

US EU Japan S. Korea Australia

Total 3 21 9 6 11

Rheumatoid Arthritis (RA);

Ankylosing Spondylitis (AS);

Plaque Psoriasis (PP);

Crohn’s disease; Ulcerative

colitis

Infliximab

(1)

Infliximab (3) Infliximab (1) Infliximab (2) Infliximab (1)

Cancer; Haematopoietic stem

cell transplantation;

Neutropenia

Filgrastim

(1)

Filgrastim (8) Filgrastim (3) Filgrastim (3)

E.g. RA, AS, PP, Juvenile

Arthritis

Etanercept

(1)

Etanercept (1) Etanercept (2)

Growth hormone deficiency;

Turner syndrome

Somatropin (1) Somatropin (1) Somatropin (1) Somatropin (2)

Anaemia Epoetin alfa (3)

Epoetin zeta (2)

Epoetin alfa (1)

Darbepoetin alfa (1)

Epoetin lambda (3)

Diabetes Insulin glargine (1) Insulin glargine (2) Insulin glargine (1)

Infertility Follitropin alfa (2) Follitropin alfa (1)

Breast cancer, gastric cancer Trastuzumab (1)


Data and market exclusivity (Regulatory Data Protection)

for originator (reference) products

11

US EU Japan South Korea Australia

Total RDP

(years)

12 10 (+1) New drug = 8

Improvement = 4-6

New drug = 6

Improvement = 4

5

Same as for

NCEs?

No; NCEs get

5 years

Yes Yes Yes Yes

Data

exclusivity

42 U.S.C. §

262(k)(7)(B)

4 Years

(cannot file

aBLA within

first 3 years

after

reference

product

approval)

Art 10(1) of 2001/83/EC:

8 Years

(cannot file biosimilar

marketing authorisation

application (MAA) within 8

years of approval of the

reference product)

Data exclusivity derives

from Post Marketing

Surveillance (PMS).

During PMS period,

originator data cannot be

referenced.

Pharmaceutical Affairs

Law Art. 32 (1) and Art.

42 (5); Regulation on

Drug Safety 22.1.

Data exclusivity

derives from PMS.

During PMS period,

originator data cannot

be referenced.

Therapeutic

Goods Act

Section 25A:

data is protected

for 5 years from

the date on

which the

reference

product was

registered

Market

exclusivity

42 U.S.C. §

262(k)(7)(A)

8 Years

(can file aBLA

but approval

cannot be

given until 12

year period

expires)

Art 10(1) of 2001/83/EC:

2 Years

(can file MAA but cannot

enter the market until

after 2 years)

1 Year Extra available if

a new indication brings a

“significant clinical

benefit"

No separate protection

but in practice some

delay reflecting

processing of biosimilar

application

No separate

protection but in

practice some delay

reflecting processing

of biosimilar

application

No separate

protection but in

practice some

delay reflecting

processing of

biosimilar

application


Substitution and interchangeability

12

US EU Japan South

Korea

Australia

Statutory

framework for

substitution?

Yes

Federal law:

BPCIA (42 USC

§262)

[interchangeability]

State law: 23

states have

enacted legislation

No EU-level

legislation

National law

varies

Ministry of Health,

Labour and

Welfare’s

“Roadmap to

promote further use

of generics” (April

2013) encourages

substitution

Yes

Pharmaceuti

cal Affairs

Law Art.

27(2):

permits

substitution

of certain

drugs

Yes

National Health Act

1953 (as amended by

National Health

Amendment

(Pharmaceutical

Benefits) Act 2015)

Pharmacy-

level

automatic

substitution

possible?

Yes – in some

states but only if

“interchangeable”

and other

conditions met e.g.

must notify

physician

Yes – but in very

few countries

(e.g. FR) and

only subject to

physician

consent

Many countries

have passed

legislation

against it (e.g.

UK, DE, IE, ES,

SE, NO & FI)

Not for biosimilars Not for

biosimilars

Yes – Pharmaceutical

Benefits Advisory

Committee (PBAC)

may “a-flag” products

for substitution.

Biosimilar infliximab

has been

recommended for

pharmacy substitution

(Dec 2015).


Map of US state enactment of substitution laws

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Map of EU substitution rules

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(Source: Mendoza, C. et al (2015): ISPOR 18th Annual Congress, Milan)


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Patent issues

Biologic Patent Expiry matrix: US and EU

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Year of US patent expiry

Ye

ar o

f EU

pa

ten

t exp

iry


Features of patent office post-grant challenges

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USPTO PGR

(AIA patents)

USPTO IPR EPO

Opposition

JPO Opposition

Deadline < 9 months from

issue

> 9 months from

issue

< 9 months from

grant

< 6 months from grant

Timescale 12-18 months 12-18 months 18-30 months 12 months

Applicant interest Not necessary Not necessary Not necessary Not necessary

Applicant identity Applicant must be

identified

Applicant must be

identified

Can be anonymous

(“straw man”)

Can be anonymous (“straw

man”)

Grounds available All grounds of

unpatentability

Novelty and inventive

step based on

documents

All grounds of

unpatentability

save for lack of

clarity / unity

Novelty, inventive step,

added matter, insufficiency,

unpatentable subject matter

Discovery Limited Limited None None

Litigation estoppel Yes Yes No No

Fee (USD) c30,000+ c23,000+ c1000 c150 + 20 per claim

Invalidation rate 100% (based on 3

decisions)

70% revoked 30% revoked

40% amended

-


Biosimilars patent litigation

18

Drug US EU (UK) South Korea

Filgrastim Amgen v Sandoz (pending)

Amgen v Teva (settled)

Pegfilgrastim Amgen v Sandoz (pending)

Amgen v Apotex (pending)

Infliximab Hospira v Janssen (dismissed)

Celltrion v Kennedy Trust (dismissed)

Janssen v Celltrion (pending)

Hospira v Mathilda and Terence

Kennedy Institute (settled)

Epoetin alfa Amgen v Hospira (pending)

Insulin glargine Sanofi v Eli Lilly (settled)

Etanercept Immunex v Sandoz (pending)

Trastuzumab Hospira v Genentech I (2 patents

revoked; upheld on appeal)

Hospira v Genentech II

(2 patents revoked; upheld on appeal)

Hospira v Genentech III

(patent revoked; pending appeal)

Celltrion v Roche

(patent revoked;

appeal pending)

Celltrion v Roche

(patent linkage case)

Rituximab Celltrion v Biogen (settled)

Hospira v Biogen (settled)

Patent linkage case

Adalimumab Fujifilm v AbbVie (pending)

Samsung Bioepis v AbbVie (pending)

Patent linkage case

AIPPI Pharma Session 2: BiosimilarsS

ourc

e: court

dockets

and o

ther

public

ly a

vaila

ble

info

rmation

19

Anti-trust issues

20

Thank you

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