Biosimilars Market Update Panel:

Matthew Brougham Consultant Economist, Brougham Consulting Inc

Mark Jackson Consultant Pharmacist, TELUS Health

Dr. Ed Keystone Professor of Medicine, University of Toronto

Moderator:

Suzanne Lepage Suzanne Lepage Consulting, Inc.

March 23, 2016

Biosimilars Market Update 2

Agenda

Why are we discussing biosimilars? 1

Biosimilars overview 2

What is happening in the rest of the world with biosimilars? 3

Payer Considerations 4

Biosimilars In Private Drug Plans 5

Biosimilars Market Update 3

Panel

Panelist Perspective

Matthew Brougham Consultant Economist, Brougham Consulting Inc.

Public Policy

Mark Jackson Pharmacist, TELUS Health

Private Drug Plan Manager

Dr. Ed Keystone Rheumatologist, Professor of Medicine, University of Toronto

Prescriber

Why are we discussing Biosimilars?

1

Biosimilars Market Update 5

Why are we discussing Biosimilars?

Biosimilars may offer potential cost relief from the brand name biologic medications and result in drug plan savings

Biosimilars present unique regulatory and reimbursement challenges

In 2015 TELUS Health adjudicated $703.2 million for biologic drugs –19% of the total eligible drug costs –2.6% of total claims

Biosimilars overview

2

Biosimilars Market Update 7

What’s in a name?

Region Term Substitution?

Canada: Subsequent Entry Biologic (SEB) No

US: Biosimilar Standards Not Developed

Europe: Follow on Biologic No

Australia: Biosimilar Yes, In Some Cases

Biosimilars Market Update 8

What’s in a name?

Term What? Who?

Interchange or Generic Substitution

Replace brand product with interchangeable generic Pharmacist

Switching or Therapeutic substitution Replace a product with a different one Prescriber

Biosimilars Market Update 9

What Health Canada Says…

Health Canada definition: “An SEB is a biologic drug that enters the market subsequent to a version previously authorized in Canada, and with demonstrated similarity to a reference biologic drug.”1

1 Health Canada Guidance for Sponsors: Information and Submission Requirements for Subsequent Entry Biologics (SEBs), 2010/03/05

....but not identical to the original medicine Biosimilars are similar...

Biosimilars Market Update 10

Size & Complexity – Small Molecule Drugs & Proteins

Small Molecule Drug Large Molecule Drug Large Biologic

Size

Aspirin 21 atoms

hGH ~ 3000 atoms

lgG Antibody ~ 25,000 atoms

Complexity

Bike ~ 20 lbs

Car ~ 3000 lbs

Business Jet ~ 30,000 lbs (without fuel)

Biosimilars Market Update 11

Chemical Drug Laboratory

Biologic Drug Laboratory

Biosimilars Market Update 12

Chemical Drugs Biologics

Generic Drug Biosimilar

Submission Abbreviated new drug submission

New drug submission requires clinical trials.

Bioequivalence Pharmacist Substitution

Physician authorize

Biosimilars Market Update 13

Biosimilars Approved in Canada

Brand Reference Biosimilar Biosimilar Approval Date Discount

Genotropin Omnitrope 4/20/2009 25.54%

Remicade Inflectra 1/15/2014 46.84%

Lantus Basaglar 9/1/2015 15.00%

Neupogen Grastofil 12/7/2015 16.67%

Biosimilars Market Update 14

Indication Extrapolation

Biosimilar is approved for each of the same indications as a branded originator Regardless of whether clinical testing has been carried out for each indication

Rheumatoid

Arthritis Ankylosing Spondylitis

Psoriatic Arthritis Psoriasis

Crohn’s Disease (Adult)

Crohn’s Disease

(Pediatric)

Ulcerative Colitis (Adult)

Ulcerative Colitis

(Pediatric)

REMICADE

INFLECTRA (extrapolated)

(extrapolated)

March 11, 2016 - CADTH request for input from for Inflectra (infliximab) for Crohn’s disease

and Ulcerative Colitis (by May 2, 2016). Submission date April 8, 2016 (Tentative)

https://www.cadth.ca/infliximab-19

*First Canadian SEB Approved under new guidance January 15, 2014

Biosimilars Market Update 15

Biosimilar Pipeline

Brand Name Earliest Patent Expiry Date

Last Patent Expiry Date

Potential Biosimilar Approval

Enbrel February 2023 Summer 2016

Humira Feb 2017 April 2025 February 2017

Neulasta July 2024 2017

Eprex May 2015 2017 or later

Lucentis March 2016 April 2018 April 2018

Erbitux March 2016 2017

Herceptin August 2017 May 2021 August 2017 or later

Avastin April 2018 April 2018 April 2018

Rituxan June 2018 August 2020 June 2018

Biosimilars Market Update 16

Biosimilar Pipeline

Brand Name Earliest Patent Expiry Date

Last Patent Expiry Date

Potential Biosimilar Approval

Enbrel February 2023 Summer 2016

Humira Feb 2017 April 2025 February 2017

Neulasta July 2024 2017

Eprex May 2015 2017 or later

Lucentis March 2016 April 2018 April 2018

Erbitux March 2016 2017

Herceptin August 2017 May 2021 August 2017 or later

Avastin April 2018 April 2018 April 2018

Rituxan June 2018 August 2020 June 2018

March 9, 2016 – CADTH – Call for Patient Input: SEB for Etanercept (Enbrel)

CADTH has received the following drug submission(s) and/or notice(s) of pending

submission(s). https://www.cadth.ca/news/call-for-patient-input-

etanercept

Prescriber Perspective

What is happening in the rest of the world with biosimilars?

3

Biosimilars Market Update 19

United States

Biosimilar product : approved based on showing it is highly similar to an FDA-approved biological product Interchangeable biological product Biosimilar to an FDA-approved reference product Meets additional standards for interchangeability (in development)

First biosimilar approved (March 6 2015)

Zarxio (filgrastim-sndz) biosimilar to Amgen Inc.’s Neupogen (filgrastim) Approved as biosimilar - not as an interchangeable product.

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/ http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm436648.htm

Biosimilars Market Update 20

Indication Extrapolation (United States)

FDA advisory committee recommended approval of Celltrion’s infliximab biosimilar, CT-P13, for the same indications as its reference product, Remicade (February 9, 2016)

Rheumatoid

Arthritis Ankylosing Spondylitis

Psoriatic Arthritis Psoriasis

Crohn’s Disease (Adult)

Crohn’s Disease

(Pediatric)

Ulcerative Colitis (Adult)

Ulcerative Colitis

(Pediatric)

REMICADE

INFLECTRA (extrapolated)

(extrapolated)

*First Canadian SEB Approved under new guidance January 15, 2014

Biosimilars Market Update 21

Australia

Brands that can be substituted by the pharmacist when dispensed are indicated in the Schedule of Pharmaceutical Benefits by an ‘a-flag’ Biosimilar for listing on the PBS

– will consider whether the biosimilar and reference medicine should be substitutable – will only recommend that substitution be allowed where the clinical evidence supports this

http://www.pbs.gov.au/info/publication/factsheets/biosimilars/biosimilar-medicines-factsheet-for-healthcare-professional

Brand Biosimilar “a-flag”

Remicade (infliximab) Inflectra (infliximab) Approved

Neupogen (filgastrim) Nivestim (filgastrim) Rejected

Lantus (insulin glargine) Basaglar (insulin blargine) Under consideration

Biosimilars Market Update 22

United Kingdom

Introducing biosimilar versions of infliximab: Inflectra and Remsima

Summary of issues considered of significance to the NHS, but not NICE guidance

Not presented as best practice but as real-life examples of how NHS sites have planned and managed the introduction of biosimilars.

1. University Hospital Southampton NHS Foundation Trust - Inflammatory Bowel Disease (IBD) Safe switch program started in April 2015

2. University College London Hospitals NHS Foundation Trust - Agreement reached for patients starting a new course of infliximab in the IBD service to be prescribed a biosimilar

http://publications.nice.org.uk/introducing-biosimilar-versions-of-infliximab-inflectra-and-remsima-htta329/introduction

Biosimilars Market Update 23

Norway

The NOR-SWITCH Study The purpose of this study is to assess the safety and efficacy of switching

from Remicade to the biosimilar treatment Remsima in patients with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn's disease and chronic plaque psoriasis.

Estimated Study Completion Date: January 2017

https://clinicaltrials.gov/ct2/show/NCT02148640

Canadian Impact

Payer Considerations

4

Biosimilars Market Update 26

Reviewer Date Recommendations

CADTH/CDR December 23, 2014 • Inflectra™ listed in accordance with Health Canada

approved indications • List in a manner similar to Remicade™

Quebec February 1, 2015 • Lowest price method (LPM) • Reimbursement of Remicade™ allowed for patients

who received before April 24, 2015

British Columbia February 19, 2016

• NEW patients covered for Inflectra™ only • Patients who previously received Special Authority

coverage for Remicade™ will continue to receive coverage

Ontario February 25, 2016

• Inflectra™ added as Limited Use (LU) for new and existing patients

• No new requests for Remicade™ • Patients who have an existing EAP approval for

Remicade™ can continue coverage

Public Payer Reviews of Biosimilars

Biosimilars Market Update 27

Pharmacy regulatory authorities (switching)

Provinces regulate when pharmacists can switch drugs without consulting the prescribing physician

Health Canada recommended against the automatic substitution of an originator with a biosimilar.

Only AB has made a statement about biosimilars

“subsequent entry biologics are not eligible for review as interchangeable products”

https://www.ab.bluecross.ca/dbl/pdfs/dbl_full_list.pdf

https://www.ab.bluecross.ca/dbl/pdfs/ahwdbl_sec1_critint.pdf

Potential Impact on Private Drug Plans

5

Biosimilars Market Update 29

What policies will encourage use of biosimilars in private drug plans?

Biosimilars are different than traditional generic drugs

Traditional drug plans will NOT generate savings from biosimilars

Pharmacist can’t automatically switch to biosimilar

What strategies should plan sponsors consider to encourage biosimilar use?