Webinar 3: (Nov 6 2020). PMPRB: Friend or Foe of Rare Disease Drug Strategy. Webinar 3 in CORD’s Rare Drug Strategy Consultation, a multi-stakeholder panel will consider the potential impact of the PMPRB revised guidelines on entry and access of rare disease therapies, using “real” case examples. Stakeholders will be invited to deliberate on alternatives to the PMPRB guidelines that could better meet the Triple Aim of “timely appropriate patient access”, “optimal, sustainable healthcare expenditure”, and “non-excessive industry compensation that incentivizes launching new therapies and future R&D.” Presentation: Kimberly Robinson, Director, Pricing & Market Access, PDCI Kim Steele, Director, Government and Community Relations, Cystic Fibrosis Canada Dr. Leanne Ward, Professor, Medical Director of the CHEO Bone Health Clinic, Scientific Director of the Ottawa Pediatric Bone Health Research Group Fred Horne, Former Alberta Minister of Health and Senior Advisor to 3Sixty Public Affairs Marissa Poole, Country Lead, Sanofi Canada and General Manager, Sanofi Genzyme Canada

1. Countdown to:
Canada’s Rare Drug Strategy 2022
Fall 2020
- Webinar 3
PMPRB: Friend or Foe of Rare Disease Drug
Strategy?
November 6, 2020

2. Canada’s Rare Opportunity of a Lifetime!
v (Exp) Oct 2020: Patented Medicines Pricing Review Board new guidelines “designed
to assure non-excessive pricing of rare disease drugs”
v Sep 2020: Speech from the Throne, government committed to an overall Rare
Disease Strategy, recognizing that:
v optimal drug access is premised on accurate diagnosis, expert clinical care,
supportive programs
v Feb 2019: Canadian government committed $1 billion to a national Rare Disease
Drug Strategy to be put in place in 2022
v Jun 2019: Pharmacare for All (Hoskins Report) “distinct pathway for consideration of
expensive drugs for rare diseases and …
v “a national expert panel to work with patients and their clinicians to determine
which rare disease drugs should be funded for which patients”
v Nov 2018: Provincial/Territorial Expensive Drugs for Rare Diseases Working Group
announced the development of a Supplemental Process for managed access to
complex/specialty drugs [including rare disease drugs]
v Nov 2018: Modernization of drug regulatory process, Health Canada produced a
designated “regulatory approach to drugs for rare diseases: orphan drugs.”

3. Countdown to Canada’s Rare Drug Strategy 2022:
Webinar Series
WEBINAR 1
OCT 9
@ 12PM (ET)
Time for a
Canadian Orphan
Drug Policy
WEBINAR 2
OCT 23
@ 12PM (ET)
Preventive & Risk
Reduction
Therapies
WEBINAR 3
NOV 6
@ 12PM (ET)
PMPRB: Friend or
Foe – Rare Disease
Drug Strategy
WEBINAR 4
NOV 20
@ 12PM (ET)
Streamlined
Regulatory, HTA,
Pricing
WEBINAR 5
DEC 4
@ 12PM (ET)
Innovative
Funding for Rare
Disease Drugs

4. Cross Canada Consultation Dates (TBC)
• National consultation forum: December 2020
• Hot Topics and Pivotal Challenges January to June 2021
• Provincial consultation forums: January to April 2021
• “What We Heard” Consolidated Feedback: May 2021
• Public Consultations (Survey and focus groups): June to August 2021
• Collaborative Document: October 2021
• Ready to go on January 1, 2022

5. Webinar 3: PMPRB: Friend or Foe of
Rare Disease Drug Strategy?
What are Key Issues?
• How do PMPRB guidelines impact entry/access for rare disease drugs?
• How does “Triple Aim” help us focus on “right” drug price?
• What are Canadian (ethical) principles that can guide drug pricing?
• What are alternatives to how PMPRB is implementing economic factors?

6. Webinar 3: PMPRB: Friend or Foe
of Rare Disease Drug Strategy?
Panelists
• Kimberly Robinson, PDCI
• Kim Steele, Cystic Fibrosis Canada
• Dr. Leanne Ward, CHEO Bone Health Clinic
• Marissa Poole, Sanofi (Genzyme) Canada
• Fred Horne, Former Alberta Minister of Health
• Moderator: Durhane Wong-Rieger, CORD

7. Recap and Update on Changes in PMPRB Federal Regulations
• Changes on How PMPRB Sets Prices:
- NEW: List of comparator countries to set Maximum
List Price: Drop 2 highest and add 5 lower priced
countries
- NEW: Regulated Maximum Rebated Price (MRP)
unilaterally set by PMPRB using new economic
factors
- NEW: Arbitrary, uniquely Canadian MRP cap set
using cost/QALY and therapeutic class levels
determined by staff
New list (PMPRB11)
FRANCE UK
GERMANY ITALY
SWEDEN AUSTRALIA
BELGIUM
JAPAN
NORWAY
NETHERLANDS
SPAIN
USA
SWITZERLAND

8. • Economic Factors
• Economic Value – 4 categories with increasing requirement for rebate
• DRDs most likely to fall in highest rebate category due to “quality of
evidence” and routinely high costs per quality adjusted life year (QALY)
• Again, market entry to Canada is likely to be delayed or not tenable
8
Value Threshold Rebate Required
Level I $200,000 per QALY 20%
Level II $150,000 per QALY 30%
Level III $150,000 per QALY 40%
Level IV $100,000 per QALY 50%
Economic Factors in Price Setting that are Disadvantageous to
Rare Diseases

9. Moving Canada to the lower end of OECD
3.21
1.06 1.00 0.97 0.94 0.94 0.92 0.89 0.88 0.86 0.85 0.84 0.83 0.83 0.81 0.81 0.80 0.80 0.79 0.79 0.78 0.76 0.74 0.72 0.71 0.70 0.69 0.69 0.67 0.67
0.54
0.34
USA
Sw
itzerlandCanadaGerm
any
New
ZealandM
exico
Japan
ChileAustriaSw
eden
ItalyFinland
UKIreland
OECD
M
EDIAN*Hungary
Spain
NetherlandsBelgium
Luxem
bourgNorw
ayFranceAustraliaPortugalSlovakia
Czech
RepublicPolandGreeceEstoniaSlovenia
South
KoreaTurkey
Average Foreign-to-Canadian Price Ratios, Patented Medicines, OECD, 2017
Calculated at medicine level for medicines with prices available in at least three foreign markers
Source: From Figure 21 of the PMPRB Annual Report 2017; MIDASTM database, 2017, IQVIA. 40-70%
Current comparator
New comparator
Canadian regulated public prices
drop by ~20% and potentially further
based on therapeutic class comparison
(TCC) test
Further reductions of net (confidential)
prices bring total regulated reductions to as
much as 50% off median international price
(MIP)
PMPRB 11 median = 0.80

10. Drug Development
Health Canada
Review ($)
Patented Medicine
Prices Review Board
Health Technology
Assessment ($)
Hospitals
Patient Access
Public Drug Plans
PMPRB new process
Private Drug Plans
NoC + 12-24+ months to
access
Challenging predictability

11. Timely appropriate
patient access
Optimal sustainable
healthcare expenditure
Incentivizing developer
compensation
Triple Aim of “Right Drug Pricing”

12. PMPRB =
“non-excessive
price
Payers =
“value-based”
price
Industry =
negotiated
rebated price
Patient-centred
access
Pricing Balance: PMPRB, pCPA, Developers

13. PMPRB
Patient-centred
access
Innovative
Industry
Payer
Supply System
Collapse
What happens when PMPRB Usurps ALL Pricing Control:
Maximum List Price, Value-Adjusted Price, Rebated Price
PMPRB: Tipping Balance to Price Control

14. Case Studies for Discussion

15. Case of Lung Disease
• AF: progressive, genetic lung disease; inability to breathe over time; premature death
• AF gene mutation: dysfunctional regulator protein; mucus in organs becomes thick and sticky
• AF affects about 1 in 4,000 persons with about 4,500 in Canada.
• NEW drug therapies: “modulators” improve performance of AF protein (ONE Company)
o “Single” modulator, AB, effective for 5% of AF patients.
o 2-drug combo, ABC, more efficient, fewer side effects, and more patients.
o 3-drug combo ABC+D, effective for up to 90% (nonresponsive to previous)
• Pills taken orally twice a day. Common nonserious side effects with uncommon serious risk of
increased liver enzymes.
• List prices: $300,000 annum AB; $310,000 annum AB+C; $325,000 annum ABC+D.
• HTA (ICER) of $100,000 - $150,000/QALY: AB @ $68,000 – $87,000; AB+C @ $71,000 - $90,000;
ABC+D: $75,000 - $94,000

16. Neuromuscular Case: LHD
• LHD: genetic, progressive disorder; muscle weakness; heart, lung and liver damage
• LHD gene produces protein essential to muscle functioning; protein level varies by
mutation and determines symptom onset, disease progression, severity of symptoms
• LHD affects about 1 in 50,000 individuals with about one-third severe
• 1st drug, EXM22, bioengineered copy dysfunctional protein; injected into spinal cord
every four months; does not reverse symptoms but delays progression
• 2nd drug, RE12, “boosts” LHD protein functioning; results similar to EXM22; daily oral
therapy with less risk and side effects.
• 3rd drug, GZ02, one-time injected gene therapy; whiceplaces the defective gene with a
functioning version of the gene. So, the patient will produce the protein ostensibly
forever.
• List prices: EXM22m $300,000 annum; RE12 $350,00 annum; GZ02 one-time $2.5
million.
• HTA (ICER) of $100,00 - $150,000/QAY: EXM22 @ $36,000 - $65,000 anumn; RE12 @
$40,000 - $75,000 annum; GZ02 @ $310,000 - $900,000 one time.