Will CADTH’s proposed streamlined approach to review of biosimilars serve the needs of all stakeholders? Helen Mai, pCODR What is the current evidence base for biosimilars use, including switching? David Zante, Janssen Canada What is the current status of clinical use of biosimilars; globally and locally? Jennifer Chan, Merck Canada Biosimilar policy issues: A patient advocate’s perspective Andrew Spiegel, Global Colon Cancer Association Debate Panel: Is the Canadian healthcare system ready for biosimilars? Panelists: Allan Miranda, Janssen; Jennifer Chan, Merck Canada; Ned Pojskic, Greenshield; Karen Voin, CLHIA; Mina Mawani, Crohn’s and Colitis Canada, Helen Mai, pCODR

1. Biosimilars
CADTH’S PROPOSED REVISIONS TO
THE BIOSIMILAR REVIEW PROCESS
FOR CDR AND PCODR
Helen Mai, LL.B
Policy and Strategy Advisor, pCODR program
CADTH
November 2017

2. Outline
1. Overview of Public Drug Funding Process in
Canada
2. Background
a. CADTH CDR Biosimilar Review Experience
b. Context for the proposed revision to the
biosimilar review process
3. Outline of proposed revisions to CADTH’s
biosimilar process for CDR and pCODR
4. Intended Goal – Improve access to drug
therapies for patients
1

3. 2
Drug Access—Who Does What
Health Canada
Regulator
(Effect &
safety)
CDR
(CADTH)
pCODR
(CADTH)
Quebec
(INESSS)
HTA
(Assess
value)
Pan Canadian Pharmaceutical
Alliance (pCPA)
Price
negotiator
F/P/T Ministries of Health and
Cancer Agencies
Decision
maker/
funder

5. What are Biosimilars?
• Health Canada’s definition of biosimilar* drug:
• A biologic drug that obtains market authorization
subsequent to a version previously authorized in
Canada, and with demonstrated similarity to a
reference biologic drug. A biosimilar relies in part on
prior information regarding safety, efficacy and
effectiveness that is deemed relevant due to the
demonstration of similarity to the reference biologic drug
and which influences the amount and type of original
data required.
• Biosimilars are generally lower in price and may offer
potential cost savings
*Source: https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-
therapies/applications-submissions/guidance-documents/information-submission-requirements-biosimilar-biologic-drugs.html
4

6. Regulatory Approval Pathway for Biosimilars
5
Reprinted from Drug Discovery Today, Volume 20, Supplement 1, Lynne A. Bui, Susan Hurst, Gregory L. Finch, Beverly Ingram,
Ira A. Jacobs, Carol F. Kirchhoff, Chee-Keng Ng, Anne M. Ryan, Key considerations in the preclinical development of
biosimilars, pages 3-15, Copyright (2015), with permission from Elsevier

7. Background: CADTH CDR Biosimilar
Review Experience
Inflectra Grastofil Basaglar Erelzi
Brenzys
Inflectra2
July
2017
October
2016
October
2016
April
2016
March
2016
December
2014
Notes:
1. Predated current CADTH review process for biosimilars
2. Submitted for IBD indications
3. Brand Name To Be Confirmed
Omnitrope1
2009
Infliximab
Biosimilar3
Under
Review

8. Background: CADTH CDR Biosimilar
Review Experience
• CDEC Recommendations to Reimburse with Criteria
and/or Conditions
• Reasons for Recommendation:
• Acceptance of biosimilarity to reference product across
multiple indications requested for reimbursement
• Biosimilar less costly than the reference product based
on the submitted price
• Limited evidence to assess switching
• Patient input: access and cost, safety and efficacy,
regulations, surveillance, switching, patient support
programs.

9. Background: CADTH CDR Biosimilar
Review Experience
Benefits Challenges
• Avoids duplication of reviews at the
jurisdictional or agency level
• Single source for coordinating
submission requirements,
screening, stakeholder participation
and leveraging expertise
• Comparative drug cost assessment
with reference brand drug;
assessment of potential economic
implications, such as for
implementation and access
• Challenges For Committee
Recommendations
• Limited clinical data available
for assessment
• Limited evidence available to
provide a complete assessment
of switching
• Unable to undertake multi-
technology assessment (i.e., unable
to compare multiple biosimilars for
the same indication)
8

10. Select Examples of International HTA Reviews of
Biosimilars
England The National Institute for Health and Care Excellence (NICE) reviews
biosimilars as part of a Multiple Technology Appraisal (MTA), and will not
consider biosimilars in a technology appraisal separate from the reference
product.
Scotland Scottish Medicines Consortium’s (SMC) will not review biosimilars if the
reference product has been accepted by SMC/Healthcare Improvement
Scotland (HIS) for the same indication(s) and in the same population or if the
reference product was initially licensed and available prior to 31 January
2002.
Australia The Pharmaceutical Benefits Advisory Committee (PBAC) considers
biosimilars as a minor submission. Minor submissions generally relate to
requests to change existing listings that do not change the population or cost-
effectiveness of the treatment, or the listing of a new form or strength of an
already-listed medicine that has a bioequivalence or equivalence statement
from the TGA. An economic model is not necessary to support the claims
made in the submission.
Germany The Institute for Quality and Efficiency in Health Care (IQWiG) include the
assessment of the benefits and costs of drugs. IQWiG, however, does not
review biosimilars, unless specially requested by the Federal joint Committee
(G-BA).
9

11. CADTH’s Proposed Revisions to
Biosimilar Process
1. Proposed Submission Requirements
• Proposed that submitters file to CADTH shortly after
making a submission to Health Canada
• Proposed that submitters would be required to provide:
i. Select submissions requirements
ii. A completed Biosimilar Summary Dossier Template
2. Stakeholder Participation
• Proposed that stakeholder perspectives and
experiences are incorporated
10

12. CADTH’s Proposed Revisions to
Biosimilar Process (Cont’d)
3. CADTH Appraisal
• Proposed that the Biosimilar Summary Dossier will not
be brought forward to CADTH’s expert review
committees
• Proposed that CADTH would provide commentaries and
analyses on sections of the Dossier and work closely
with Health Canada to include a summary of the market
authorization of the biosimilar under review
• CADTH reserves the right to request a full submission in
limited cases
11

13. CADTH’s Proposed Revisions to
Biosimilar Process (Cont’d)
4. Transparency
• Proposed that Biosimilar Summary Dossier will be
posted on the CADTH website
• Proposed that information provided in the Dossier be
fully disclosable
12

14. Intended Goal
• Proposed that CADTH would coordinate and work in
collaboration with:
• Health Canada
• pan-Canadian Pharmaceutical Alliance (pCPA)
• participating federal, provincial and territorial public
drug plans
• provincial cancer agencies
• A streamlined approach for biosimilar reviews would
support improved access for patients
13

16. What is the current evidence base for
biosimilars use, including switching?
David Zante
Janssen Inc.
Case Study:
Infliximab (REMICADE® à CT-P13/Inflectra)

17. biosimilar
planned*
*EGALITY (etanercept) and VOLTAIRE-X (adalimumab) are interchangeability studies in psoriasis
Interchangeability Studies Have Not Been
Performed With Infliximab Biosimilar
Adapted from Dörner T et al. Nat Rev Rheumatol 2015;11:713-724.
Clinicaltrials.gov, search term: NCT03210259;
Griffiths CEM et al. Br J Dermatol 2017;176:928-938.
CD=Crohn's disease.

18. Clinical Trial Data – Switch from REMICADE
to CT-P13 (Inflectra/Remsima) in
Rheumatoid Disease

19. P L A N E T A S S T U D Y 1
Clinical Trials: Efficacy Evaluation Before and After
Switch
References: 1. Park W et al. Ann Rheum Dis. 2016. doi:10.1136/annrheumdis-2015-208783. 2. Yoo DH et al. Ann Rheum Dis. 2016. doi:10.1136/annrheumdis-2015-208786.
*At Week 54, patients were switched from REMICADE® to infliximab-dyyb.
P L A N E T R A S T U D Y 2
Results are based on patients who completed the 54-week main study and entered the open-label extension study.

20. Rates of safety events in patients who switched compared to those who
continued were not consistent between the 2 trials.
References: 1. Park W et al. [ACR abstract L15]. Presented at: Annual Meeting of the American College of Rheumatology; October 25-30, 2013; San Diego, CA. 2. Yoo D et al.
[ACR abstract L1]. Presented at: Annual Meeting of the American College of Rheumatology; October 25-30, 2013; San Diego, CA.
AE=adverse event; AS=ankylosing spondylitis; RA=rheumatoid arthritis;
TEAE=treatment-emergent adverse event; TESAE=treatment-emergent
serious adverse event.
Clinical Trials: Safety Evaluation After Switch
P L A N E T A S S T U D Y 1 P L A N E T R A S T U D Y 2

21. S T U D Y D E S I G N
Efficacy was sustained in extended follow-up post-switch in this regional
clinical trial, however safety events were higher in the switch group.
Data Source: Japan College of Rheumatology
Endpoints: Incidence of adverse events during long-term treatment and after switching
Study duration: Main study observed through Week 54; extension study observed through Week 167
Tanaka Y, Yamanaka H, Takeuchi T, et al. Japan College of Rheumatology. Safety and efficacy of CT-P13 in Japanese patients with rheumatoid arthritis in an extension phase or after switching
from infliximab [published online September 1 2016]. Mod Rheumatol. 2016; DOI: 10.1080/14397595.2016.1206244..
Japanese Clinical Trial: Efficacy and Safety Evaluation
After Switch

22. Observational Switch Data -
Rheumatology

23. Independent, Observational Experience in One-Time
Switches in Rheumatology with CT-P13
When reported,
efficacy rates post-
switch range from
sustained (Abdalla,
Rubio) to 30% loss
of response
(Gentileschi)
8 cohorts available
(Europe)
2 publications
6 abstracts/posters
Safety
When reported,
adverse event rates
were observed to be
comparable to
historical rates with
REMICADE®
Discontinuation rates
due to loss of
response and/or
AEs range from 6%
(Batticciotto) to 30%
(Nikiphorou,
Gentileschi)
Efficacy Discontinuations
Nikiphorou et al. Expert Opin Biol Ther 2015;15:1677-83; Gentileschi, et al. Expert Opin Biol Ther 2016; doi:
10.1080/14712598.2016.1198765; Batticciotto et al. Arthritis Rheumatol 2016;68(Suppl 10), abstract 721; Glintborg et al. Arthritis
Rheumatol 2016;68(Suppl 10), abstract 951; Rubio et al. Ann Rheum Dis 2016;75(Suppl 2):1006, abstract AB0310; Sheppard et al. Ann
Rheum Dis 2016;75(Suppl 2):1011, abstract AB0322; Tweehuysen et al. Arthritis Rheumatol 2016;68(Suppl 10), abstract 627; Abdalla et
al. Ann Rheum Dis 2016;75(Suppl 2):223, abstract THU0120.

24. Observational Switch Experience with CT-P13 in
Rheumatology
28%
30% *
6%
15%
9%
20%
23%
15%
0%
5%
10%
15%
20%
25%
30%
35%
Nikiphorou
(Finland)
Gentileschi
(Italy)
Batticciotto
(Italy)
Glintborg
(Denmark)
Rubio
(Spain)
Sheppard
(UK)
Tweehuysen
(Netherlands)
Abdalla
(Ireland)
18
/3
9
7/
23
Sample size 39 23 36 792 53 25 192 34
Previous
REMICADE®
Treatment
4.1 years
(mean)
6 years
(mean)
76 months
(median)
6.6 years
(median)
NR NR NR
70
months
(mean)
Follow-up
11 months
(median)
1.7
months
(mean)
6 months
11 months
(median)
9 months NR 6 months
15.8
months
(mean)
Nikiphorou et al. Expert Opin Biol Ther 2015;15:1677-83; Gentileschi, et al. Expert Opin Biol Ther 2016; doi:
10.1080/14712598.2016.1198765; Batticciotto et al. Arthritis Rheumatol 2016;68(Suppl 10), abstract 721; Glintborg et al. Arthritis
Rheumatol 2016;68(Suppl 10), abstract 951; Rubio et al. Ann Rheum Dis 2016;75(Suppl 2):1006, abstract AB0310; Sheppard et al. Ann
Rheum Dis 2016;75(Suppl 2):1011, abstract AB0322; Tweehuysen et al. Arthritis Rheumatol 2016;68(Suppl 10), abstract 627; Abdalla et
al. Ann Rheum Dis 2016;75(Suppl 2):223, abstract THU0120.
Discontinuations(%)
*Disease relapse
NR: not reported

25. Observational Switching Data – Irritable
Bowel Disease (Crohn’s Disease/
Ulcerative Colitis)

26. Observational Switch Experiences in IBD with
CT-P13
When reported,
effectiveness rates
post-switch range
from sustained
(Guerra Veloz
abstracts) to 12%
loss of response
(Fiorino)
When reported,
adverse event rates
were observed to be
comparable to
historical rates with
REMICADE®
When reported,
rates of
discontinuation
range from 3%
(Buer)
to 38%
(Sieczkowska)
14 cohorts reported
(Europe, Korea, Japan)
7 publications
7 abstracts/posters
Efficacy Safety Discontinuations
Kang et al. Dig Dis Sci. 2015;60:951-6; Yoon Suk Jung et al. J Gastroenterol Hepatol. 2015;30(12):1705-12; Park et al. Expert Rev Gastroentrol Hepatol 2015;9(S1):S35-S44;
Sieczkowska et al. J Crohns Colitis 2016;10(2):127-32; Smits et al. J Crohns Colitis 2016; doi: 10.1093/ecco-jcc/jjw087; Buer, et al. J Crohns Colitis 2016; doi:
10.1093/ecco jcc/jjw166; Fiorino et al. Inflamm Bowel Dis 2017; doi: 10.1097/MIB.0000000000000995; Bettey, et al. J Cronhs Colitis 2016;10(Suppl 1):S43-4, abstract
DOP029; Kolar et al. J Crohns Colitis 2016;10(Suppl 1):S45-6, abstract DOP032; Hamanaka et al. J Crohns Colitis 2016;10(Suppl 1):S260, abstract P329; Díaz Hernández et
al. J Crohns Colitis 2016;10(suppl 1):S327, abstract P449.; Guerra Veloz et al. J Crohns Colitis 2016;10(suppl 1):S328-9, abstract P452; Guerra Veloz et al. J Crohns Colitis
2016;10(suppl 1):S405, abstract P600; Hlavaty et al. J Crohns Colitis 2016;10(Suppl 1):S433, abstract P655.

27. 22%
6%
4%
14%
4%
38%
3%
12%*
33%
0%
5%
10%
15%
20%
25%
30%
35%
40%
Kang
(Korea)
Smits
(Netherlands)
Kolar
(Czech Rep)
Jung
(Korea)
Diaz Hernandez
(Spain)
Sieczkowska
(Poland)
Buer
(Norway)
Fiorino
(Italy)
Hlavaty
(Slovakia)
Observational Experience With Switching in IBD
Previous REMICADE® Treatment
N/A
25
months
3
years
N/A
4
years
Approx.
67
Weeks
57
months
(UC)
87
months
(CD)
28
months# N/A
Kang et al. Dig Dis Sci. 2015;60:951-956. Smits et al. J Crohns Colitis 2016; doi : 10.1093/ecco-jcc/jjw087. Kolar et al. J Crohns Colitis 2016;10(Suppl
1):S45-6, abstract DOP032. Jung et al. J Gastroenterol Hepatol. 2015;30(12):1705-1712. Díaz Hernández et al. J Crohns Colitis 2016;10(suppl 1):S327,
abstract P449. Sieczkowska et al. J Crohn’s Colitis 2016;10(2):127-132. Buer et al, J Crohns Colitis 2016; doi: 10.1096/ecco-jcc/jjw166. Fiorino et al.
Inflamm Bowel Dis 2017; doi: 10.1097/MIB.0000000000000995. Hlavaty et al. J Crohns Colitis 2016;10(Suppl 1):S433, abstract P655.
Sample size
9 83 74 36 72 39 143 97 12
Follow-up
42.5
Weeks
(median)
16
Weeks
24
weeks
54
Weeks
6
months
2-11
months
6
months
6
months
48
weeks
*Loss of response
Reported in: Fiorino J
Crohns Colitis 10(Suppl
1):S376-7, abstract
P544.
#Assumption is q8w
infusion schedule
Discontinuations(%)

28. THE NOR-SWITCH STUDY
A MULTICENTRE, RANDOMIZED, DOUBLE-BLIND,
PARALLEL-GROUP STUDY TO EVALUATE THE SAFETY
AND EFFICACY OF SWITCHING FROM INNOVATOR
INFLIXIMAB TO BIOSIMILAR INFLIXIMAB IN
PATIENTS WITH RA, AS, PsA, UC, CD AND PsO
Abstract LB15
Latebreaker Session – UEGW 2016
Jørgensen K, Olsen I, Goll G, Lorentzen M, Bolstad N, Haavardsholm E,
Lundin K, Mørk C, Jahnsen J, Kvien T (Norway)

29. Study Design
Main Study Open-Label Extension
R
1:1
CT-P13 CT-P13
INX CT-P13
Pts with RA, SpA,
PsA, UC, CD or PsO
on stable dose of INX
≥ 6 mo
W0 W78W52
NOR-SWITCH
• Aim: To examine switching from originator to biosimilar infliximab regarding
efficacy, safety and immunogenicity in stable patients on originator drug
• Primary endpoint: Occurrence of disease worsening at W52
– UC: increase in p-Mayo score of ≥ 3 and a p-Mayo score of ≥ 5
– CD: increase in HBI of ≥ 4 and a HBI score of ≥ 7
• Assumptions:
– 30% disease worsening in the INX arm*
– Non-inferiority margin: 15%
INX: originator infliximab (Remicade®); CT-P13: biosimilar infliximab (Remsima®)
*From Jørgensen K, et al. UEGW 2016, Abstract LB15, Late-Breaker Oral Presentation.

30. Results
Diagnosis
INX
(n=202)
CT-P13
(n=206)
Adjusted Rate
Difference (95% CI)
Rheumatoid
arthritis
11 (36.7%) 9 (30.0%) 4.5% (-20.3-29.3%)
Spondyloarthritis 17 (39.5%) 14 (33.3%) 6.3% (-14.5-27.2%)
Psoriatic arthritis 7 (53.8%) 8 (61.5%) -8.7% (-45.5-28.1%)
Ulcerative colitis 3 (9.1%) 5 (11.9%) -2.6% (-15.2-10.0%)
Crohn’s disease 14 (21.2%) 23 (36.5%) -14.3% (-29.3-0.7%)
Psoriasis 1 (5.9%) 2 (12.5%) -6.7% (-26.7-13.2%)
Overall 53 (26.2%) 61 (29.6%) -4.4% (-12.7-3.9%)
Benefits INX % Benefits CT-P13
-50 -40 -30 -20 -10 0 10 20 30 40 50
NOR-SWITCH
Jørgensen K, et al. UEGW 2016, Abstract LB15, Latebreaker Oral Presentation.

31. Phase III Randomized, Double-
blind, Controlled Trial to Compare
Biosimilar Infliximab (CT-P13)
with Innovator Infliximab in
Patients with Active Crohn’s
Disease: Early Efficacy and Safety
Results
Kim et al. Presented at ECCO #DOP061
February 17, 2017

32. Crohn’s Disease Study Design
• Phase III randomized, double-blind, parallel-group trial
• To demonstrate therapeutic non-inferiority of CT-P13 to
REMICADE (non-inferiority margin = -20%)
• 54-week study
• Dose escalation: 10 mg/kg is allowed from week 22 if worsening
CDAI: Crohn’s Disease Activity Index; CD: Crohn’s disease; IV: intravenous
Kim et al. ECCO 2017; Abstract #DOP061; www.clinicaltrials.gov, search term: NCT02096861;
Trial Trove, https://citeline.com/products/trialtrove/, search term: NCT02096861;
http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/ucm486170.htm
REMICADE® (5 mg/kg IV)
Targeted
accrual
N=220
Biologic naïve,
active CD pts
(CDAI 220-450
points)
Week 0 2 6 14 22 30 38 46 54
Primary
endpoint
Up to
Week 54
Screening
Randomization 1:1:1:1
INFLECTRA™ (5 mg/kg IV)
INFLECTRA™ (5 mg/kg IV)
REMICADE® (5 mg/kg IV)

33. Efficacy: CDAI 70, CDAI 100, Clinical
Remission at Weeks 6 and 30
69.4
60.4
42.3
74.3
64.2
45.0
0
20
40
60
80
100
CDAI-70
response
CDAI-100
response
Clinical
Remission
% of patients
77/111 81/109
75.7 72.1
55.0
75.2 73.4
56.9
0
20
40
60
80
100
CDAI-70
response
CDAI-100
response
Clinical
Remission
% of patients
71.4
61.9
42.9
75.2
64.4
44.6
0
20
40
60
80
100
CDAI-70
response
CDAI-100
response
Clinical
Remission
% of patients
CT-P13 INX
78.1 74.3
56.2
77.2 75.2
57.4
0
20
40
60
80
100
CDAI-70
response
CDAI-100
response
Clinical
Remission
% of patients
Intent-to-Treat AnalysisPer Protocol Analysis
Week 6 Week 30
67/111 70/109 47/111 49/109
84/111 82/109 80/111 80/109 61/111 62/109
75/105 76/101 65/105 65/101 45/105 45/101
82/105 78/101 78/105 76/101 59/105 58/101
Δ = 0.9
(CI: -10.6, 12.4)
Δ = -0.9
(CI: -13.1, 11.4)
Δ = -1.2
(CI: -15.4, 12.9)
Δ = -3.8
(CI: -15.9. 9.0)
Δ = -2.5
(CI: -15.8, 11.0)
Δ = -1.7
(CI: -15.5, 12.4)
Δ = -4.9
(CI: -16.9, 7.3)
Δ = -3.8
(CI: -16.7, 9.6)
Δ = -2.7
(CI: -16.2, 10.6)
Δ = 0.5
(CI: -11.3, 12.1)
Δ = -1.3
(CI: -13.3, 10.6)
Δ = -1.9
(CI: -15.2, 11.7)
Kim et al. ECCO 2017; Abstract #DOP061

34. Summary: REMICADE®àCT-P13 switching data
• Limited switch data available
• Observational Studies:
• Results are contradictory and include small sample size, non randomized,
open label design and do not address immunogenicity
• Large and well controlled trials are needed to confirm the
implications of switching anti-TNF therapy in patients with stable
disease
• Interchangeability is still a big unknown
• How many switches are needed to establish interchangeability?
• What clinical results are needed to be successful in establishing
interchangeability?
• Are multiple biosimilars for the same innovator interchangeable
with the innovator only or with other biosimilars only or both?
• To date, interchangeability between INFLECTRA™ and REMICADE®
has not been established

35. Additional Resources
CARE Perspectives on the NorSwitch Trial (Jan 26, 2017)
• http://www.careeducation.ca/gastro-publications-blog/2017/1/26/care-perspectives-on-the-
nor-switch-trial
CARE Perspective -The Impact of Biosimilars in Canada (Oct 10, 2017)
• http://www.careeducation.ca/gastro-publications-blog/2017/10/3/the-impact-of-biosimilars-in-
canada
20

36. THANK YOU
21

37. Jennifer Chan, Vice President, Policy and External Affairs
Merck Canada Inc.
Realizing the Full Potential of Biosimilars :
Opportunities and Challenges
November 7, 2017

38. “Biosimilars have been safely utilized in Europe (since 2006), Australia, Canada,
Japan, and several other countries worldwide, resulting in more than 400 million
patient-days of exposure to more than 20 biosimilars for numerous molecules,
including recombinant human growth hormone (rhGH), erythropoietin, filgrastim,
insulin, follitropin, infliximab, and etanercept.”1
Global Experience with Biosimilars
2
1. Cohen H et al. Awareness, Knowledge, and Perceptions of Biosimilars Among Specialty Physicians. Advances in Therapy (2016) 33:2160–2172

39. Penetration of anti-TNFα Biosimilars in Europe
3
19.8% 18.3%
43.0%
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
50%
Unit %
Market Share % of the reference biologic
Source: IMS MIDAS, Oct. 2016
68.6%
97.9%
0%
20%
40%
60%
80%
100%
120%
Market Share % of the reference biologic
BIOSIMILAR A BIOSIMILAR B BIOSIMILAR C

40. THE EU EXPERIENCE WITH BIOSIMILARS
4
• 23 biosimilars approved by the European Medicines Agency (EMA) since
20061
• “The evidence acquired over 10 years of clinical experience shows that
biosimilars approved through EMA can be used as safely and effectively in
all their approved indications as other biological medicines.”2
• “Over the last 10 years, the EU monitoring system for safety concerns has
not identified any relevant difference in the nature, severity or frequency of
adverse effects between biosimilar medicines and their reference
medicines.”2
1. The State of Biosimilars, A FirstWord Perspectives Report, nc Research, mars 2017
2. Biosimilars in the EU, Information guide for healthcare professionals, European Medicines Agency and European Commission, 2017

41. 5
Consensus recommendation #6:
“Currently available evidence indicates that a single switch from a bio-originator to one of its
biosimilars is safe and effective; there is no scientific rationale to expect that switching among
biosimilars of the same biooriginator would result in a different clinical outcome but patient
perspectives must be considered.”
Consensus recommendation #8:
“No switch to or among biosimilars should be initiated without the prior awareness of the patient and
the treating healthcare provider..”
Kay J et al., Consensus-based recommendations for the use of biosimilars to treat rheumatological diseases, Ann Rheum Dis.
2017 Sep 2. pii: annrheumdis-2017-211937.
LEVEL OF EVIDENCE: 1B
GRADE OF RECOMMENDATION: A

42. “Can a patient already being treated with a reference
biologic drug be switched to a biosimilar?
Switching generally refers to a one-time change from a reference biologic
drug to a biosimilar.
Health Canada recommends that a decision to switch a patient being
treated with a reference biologic drug (innovator product) to a biosimilar
should be made by the treating physician in consultation with the patient
and taking into account available clinical evidence and any policies of the
relevant jurisdiction.
For questions related to changing from one biologic drug to another,
patients should speak to their doctor.”
Health Canada’s Position on ‘Switching’
6
Health Canada, Fact Sheet: Biosimilars: https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-
radiopharmaceuticals-genetic-therapies/applications-submissions/guidance-documents/fact-sheet-biosimilars.html Accessed Oct 30, 2017

43. “A competitive and sustainable market for biosimilar and
innovator drugs could offer many benefits to the healthcare
system, including broadening access to effective biologic
treatments, reducing the cost burden and enabling savings
to be re-directed across all areas of healthcare including
funding of new innovative therapies.”1
As reported by Health Canada following the
2017 Biosimilars Workshop:
7
1.Health Canada’s 2017 Biosimilars Workshop: Summary Report: https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-
therapies/applications-submissions/guidance-documents/biosimilars-workshop.html Accessed Oct 6, 2017

44. Inflectra* Uptake in Ontario
(provincial public drug program)
8
0%
20%
40%
60%
80%
100%
120%
Jan
2016
Feb
2016
Mar
2016
Apr
2016
May
2016
Jun
2016
Jul
2016
Aug
2016
Sep
2016
Oct
2016
Nov
2016
Dec
2016
Jan
2017
Feb
2017
Mar
2017
Apr
2017
May
2017
Jun
2017
Jul
2017
Aug
2017
Sep
2017
Remicade* & Inflectra* - ODB
INFLECTRA
REMICADE
Inflectra* listed by
ODB with LU codes
(preferential for new
patients)
Source: Quintiles IMS - Pharmastat*
*All other trademarks are the property of their respective owner(s)
Inflectra* listing in inflammatory
bowel disease with LU codes
8

45. “While there has been a substantial uptake in the biosimilars for infliximab in many
OECD countries, the uptake in Canada has been low (0.2% based on private drug
plan data).”
“While the price of the biosimilar for Remicade in Canada is in line with the median
OECD level, the uptake in sales has been relatively modest to date. If the use of
the biosimilar in Canada had mirrored the median OECD use in 2015 (10.1%), it
would have translated into a $41.7 million reduction in drug expenditures.”
Is Canada Missing Out on the Biosimilar
Opportunity?
9
Patented Medicines Prices Review Board, Market Intelligence Report, Biologic Response Modifier Agents, 2015.

46. Example from the Department of Gastroenterology, Southampton General Hospital, UK1*
“A managed switching program from originator infliximab to biosimilar in IBD, using a gain-
share agreement, delivered significant cost savings and investment in clinical services while
maintaining similar patient-reported outcomes, biochemical response, drug persistence, and
adverse event profile.”
A Managed Switching Program funded via a Gain Share
Agreement
10
1. Razanskaite et al., Biosimilar Infliximab in Inflammatory Bowel Disease: Outcomes of a Managed Switching Programme. J Crohns Colitis. 2017 Jun 1;11(6):690-696.
“The principle of gain share is to distribute the cost savings between
the stakeholders, which incentivises secondary care providers to
make the most efficient use of high-cost drugs and re-invest the cost
savings in patient care such as local IBD services.”
* Outcomes of a service evaluation including 143 patients with IBD started in April 2015. All infliximab-treated IBD patients under the care of the adult IBD
service were offered the opportunity to participate. Patients were switched to biosimilar infliximab at the same dose and with the same frequency as
originator infliximab.

47. “The patient support programs aim at increasing or facilitating patient understanding of a
disease and/or treatment, better patient outcomes as well as possibly improving patient
adherence to treatment. Such programs may also serve to ensure or assist with access
and/or reimbursement of a product.”1
Patient Support Programs are important to
patients and Health Care Professionals
11
Examples of services offered by Patient Support Programs for
biological/biosimilar products:
ü Personalized phone support to patients.
ü Reimbursement support
ü Financial assistance to patients in need
ü Diagnostic tests
ü Nursing support
ü Self-injection training or infusion services.
ü Health care professional educator resources
1. Innovative Medicines Canada, Code of Ethical Practices, 2017

48. Biosimilar Policy Considerations: A
Patient Advocate’s Perspective
Andrew Spiegel, Esquire
Founder and Executive Director
Global Colon Cancer Association

49. Review: What Makes Biologics Special?
2

50. 3
Biologic vs. Chemical Medicines
SIZE: significantly larger, potential for
immunogenic reactions
STRUCTURE: more complex, cannot be
completely characterized or exactly copied
STABILITY: susceptible to light, heat,
denaturing / degradation
SENSITIVITY: even small manufacturing
changes can cause changes in efficacy
and/or adverse events
DRIFT: can change with time

51. Biologics are made in living cells and are highly complex so they cannot
be exactly copied.
Thus, Biosimilars are NOT Identical to their
reference product….…They can only be “SIMILAR”
≠
4

52. Building Patient/Physician Confidence Is Key
Naming, Labeling and Substitution are all fundamentally issues of
TRANSPARENCY and DATA.
TRANSPARENCY
& DATA
PHYSICIAN &
PATIENT
CONFIDENCE
WIDESPREAD
BIOSIMILAR
ADOPTION
ASBM’s approach has been to EDUCATE stakeholders, and to work
with regulators to promote policies which BUILD PHYSICIAN/PATIENT
CONFIDENCE IN BIOSIMILARS by requiring TRANSPARENCY and DATA.
BUILDS PROMOTES

53. 6
Two Biosimilar Policy Challenges Facing Policymakers:
Naming
How do we clearly distinguish similar medicines from one another for
purposes of tracking their use, safety and efficacy?
Substitution
When and how can this be done safely?

54. Naming
7

55. • The “scientific name” of the active ingredient in a
medicine
• Issued by the World Health Organization (WHO)
• WHO mission is to "develop, establish and promote
international standards with respect to biological,
pharmaceutical and similar products”
• While sharing an INN works well for small molecule drugs
and generic copies which are structurally identical, it
doesn’t for biologics and biosimilars…
International Nonproprietary Name (INN)

56. 9
Recent ASBM ActivityWHO and FDA: Distinguishable Naming Proposals
• Both regulators are updating their naming
systems for biosimilars.
• Distinguishability aids in clear
communication throughout treatment,
improves tracking of safety and efficacy, and
promotes manufacturer accountability.
• Both call for similar biologics (including
biosimilars) to have a shared root name
(International Nonproprietary Name/ INN)
followed by a four-letter suffix.

57. The WHO Solution: The “Biological Qualifier” (BQ)
10
A random string of 4 letters added to the International
Nonproprietary Name (INN) of the biologic, allowing it to
be distinguishable from similar biologics.
Since 2013, ASBM has been working closely with the WHO
as it develops its standard for distinguishable naming,
sharing physician perspectives from our surveys and
offering our recommendations.
We will present again at the 65th INN Consultation on
October 17th.

58. Benefits of the BQ:
CLEAR PRODUCT IDENTIFICATION - Distinguishable from reference product, and other
approved biosimilars.
CLEAR COMMUNICATION - between physician, patient and pharmacist
CLEAR PRESCRIBING & DISPENSING - Helps prevent inadvertent and inappropriate
substitution.
BETTER PHARMACOVIGILANCE - proper attribution of adverse events.
INCREASED MANUFACTURER ACCOUNTABILITY - suffixes tied to manufacturer/facility

59. Broad Support for Distinct Naming Among Physicians Globally
12
94% of Latin American
Physicians consider WHO’s BQ Proposal
to be “useful” in helping patients receive
the correct medicine. (2015)
79% of Canadian
physicians support Health Canada
issuing distinct names. (2014)
66% of US physicians support
FDA issuing distinct names. (2015)
76% of Australian
physicians support TGA issuing
distinct names (2016)

60. Biosimilar Substitution
13

61. If this headline is to be believed,
there should be great confidence
among physicians in biosimilars…

62. But … we’ve not yet seen widespread use when
physicians have a choice of using a biosimilar or the
originator
Why?

63. What is “Automatic Substitution”?
1) Physician writes a prescription 2) Pharmacist is allowed, or required, to provide
a different medicine to the patient without
communication with prescribing doctor
beforehand
X 16

64. Concerns With Automatic Substitution of Biosimilars
• Physicians need to know which medicine the patient is actually receiving
to make informed treatment decisions.
• Knowing this helps them assess the patient’s response to a particular
treatment. For example, if a patient were to stop responding, they need to
know if it is potentially due to a switch, or some other factor.
• There is often variability in patient response. The best treatment for one
patient is not the best choice for all.
• Providers and patients are best positioned to determine which medicine
will work best for their condition.

65. Issues Surrounding Biosimilar Substitution
• Under what circumstances may a pharmacist substitute a biosimilar
without the involvement of the physician?
• What communication is required between pharmacist and:
– Physician
– Patient
• What records must be kept
of the substitution?

66. • Changing your treatment may change
the control a patient has over their
condition.
• Patient and doctor should have the final
say about treatment choices- which
biologic to use, and if and when
switching is appropriate.
• If your medicine is working for you, most
doctors don’t think it is a good idea to
switch from one biologic to another for
cost reasons only.
Issues Surrounding Non-Medical Switching

67. More Data Builds Confidence
More data showing that safe use,
including safe switching, does not
result in differences in efficacy,
adverse effects or discontinuation
rates will increase physician (and
patient) confidence
20

68. World Health Assembly- June 2017
As I said at the World Health Assembly last June:
“The absence of data is not data”.
While Europe has led on biosimilar approval, they have failed to build
confidence in biosimilars through post-market data collection.

69. Summary
Patients expect that the life of
the patient should remain the
primary guiding principle of
biosimilar policy discussions-
not potential cost savings.

70. Summary
CLEAR NAMING of all biologics,
including biosimilars, is
important to physicians
worldwide to ensure their safe
use.

71. Summary
It is important to
physicians worldwide they
retain the authority to use
“do not substitute” or
“dispense as written” to
ensure the patient
receives the correct
medicine.

72. Summary
It is important to physicians
that they be informed in a
timely manner which medicine
was actually dispensed to
their patient.

73. Summary
DATA and TRANSPARENCY
during the approval process
and afterward, will build
physician confidence in
biosimilars; increasing uptake.

74. Summary
We expect, with our
physicians, to determine the
course of our treatment.
This includes choosing which
biologic medicine to use
initially -- and choosing if and
when to switch.

75. Thank you!
Andrew Spiegel, Esquire
Founder and Executive Director
Global Colon Cancer Association
andrew.spiegel@globalcca.org

76. Debate Panel
Day 2 Session 4

77. Is the Canadian healthcare system
ready for biosimilars?
• Allan Miranda, Janssen
• Jennifer Chan
• Merck Canada
• Ned Pojskic, Greenshield
• Karen Voin, CLHIA
• Mina Mawani, Crohn’s and Colitis Canada
• Helen Mai, pCODR

78. Is the Canadian healthcare system
ready for biosimilars?
Is the Canadian healthcare system ready for biosimilars?
a. Resolution: With 10+ years of experience in Europe,
switching to a biosimilars is no longer an issue.
b. Resolution: Preferential listing for biosimilars is good
for the healthcare system and good for patients.
c. Resolution: Patient preference should be the
deciding criterion on use of original biologic or
biosimilar.