This document summarizes a presentation about creating Canada's rare disease network. It discusses barriers to accessing treatments, the role of physician advocacy, and an approach taken in Manitoba and Saskatchewan to build capacity for diagnosing hereditary metabolic disorders. A key part of this approach is the "OMICS First" strategy of starting with comprehensive DNA testing rather than traditional testing. This aims to improve timelines, reduce hospital stays and tests, and lower costs while maintaining quality of care. The presentation also discusses challenges of pricing for rare disease treatments and the need for real-world evidence to be incorporated into decision making.

1. Day 2: Barriers and Opportunities Along
Pathways to Access
•Session 5: Creating Canada’s Rare Disease Network
•“Canadian De-Centralized Centres of Excellence”
Dr. Cheryl Rockman- Greenberg
Winnipeg, MB

2. No shortage of dialogue at the federal level…

3. Disclosures
• Financial Payments/Honoraria: Honoraria from Alexion,
AstraZeneca Rare Diseases
• Advisory Board or Speakers Bureau: Member of the Scientific
Advisory Committee of the Hypophosphatasia Global Patient
Registry
• Research grants or Consulting Fees: Consultant to
Saskatchewan Health and Metabolic program, Saskatoon
• Patents: 0
• Other: 0

4. Outline
• From Clinical Trials to Access: One physician’s perspective
• Role of Physician Advocacy
• Overview of the approach to building capacity and providing precision
health to Canadians in the Prairies (MB and SK) with suspected
hereditary metabolic disorders (Inborn Errors of Metabolism)
• The Canadian Prairie Metabolic Network
•
CPMN OMICS First
Canadian Prairie Metabolic Network

5. Pillars of Research
BASIC
SCIENCE
CLINICAL
TRIALS
PRECISION
MEDICINE
REAL
WORLD
EVIDENCE

6. C
l
i
n
i
c
a
l
:
O
u
t
c
o
m
e
C
l
i
n
i
c
a
l
:
T
r
i
a
l
C
l
i
n
i
c
a
l
:
B
i
o
l
o
g
i
c
B
a
s
i
c
:
A
n
i
m
a
l
M
o
d
e
l
B
a
s
i
c
:
C
e
l
l
u
l
a
r
B
a
s
i
c
:
M
o
l
e
c
u
l
a
r
H
e
a
l
t
h
S
y
s
t
e
m
D
e
s
i
g
n
H
e
a
l
t
h
E
c
o
n
o
m
i
c
s
Discovery to Practice
H
e
a
l
t
h
P
o
l
i
c
y
K
n
o
w
l
e
d
g
e
S
y
n
t
h
e
s
i
s
Valley 1 Valley 2
Basic Biomedical
Research
Clinical Science
& Knowledge
Health Decision
Making &
Clinical Practice
K
n
o
w
l
e
d
g
e
T
r
a
n
s
l
a
t
i
o
n
Figure adapted from Steven Reis and Harold Pincus
Vision of Joe Doupe
The Clinician-Scientist
Pursing Life-long Discovery & Translation

7. From Clinical Trials to Access:
One physician’s perspective
• Canada became the site of 1st clinical trial for hypophosphatasia
(HPP)
• From HPP clinical trials to ongoing challenges to access
• Responsibilities of physicians, all health care providers and advocacy
groups to improve the patient experience
• Discussing next steps:
• Real-world data

8. Public Reimbursement Timelines
Health Canada
Submission
Health Canada
Approval
(NOC/NOCc)
1-2 years
Manufacturer Submission to CDR
Pre-NOC/NOCc (up to 90 days) or post
NOC/NOCc
CDR/CDEC Listing
Recommendation to
Provinces/Territories
5-6 months
Pan Canadian
Pharmaceutical
Alliance (pCPA)
Negotiations
(price
negotiations)
Manufacturer may offer notification of a pending submission to CDR
up to 20 business days in advance of making submission. If so, CDR
will offer 35 business days timeframe for patient group input. If
manufacturer does not notify CDR, then CDR will offer 15 business
days timeframe for patient group input.
CADTH posts it on the Open Calls for Patient Input page along with
the deadline for providing input.
Provincial/Territorial
Product Listing
Decision/Agreement
Can take up to or > 2 years

9. The Asfotase Alfa Notice of Compliance with Conditions (NOCc)
Issued by Health Canada in September 2015
• The submitted indication to Health Canada for asfotase alfa is:
“for long-term enzyme replacement therapy in patients with
paediatric-onset hypophosphatasia”
• Asfotase alfa is Canadian discovered and developed to meet the
needs of HPP patients in Canada and around the world
• The NOCc issued in September 2015
• Alexion Canada made a submission to the CDR within 90 days
prior to NOCc
• CDR of CADTH recommended listing drug on provincial
formularies for pediatric – onset HPP for children under 18
years of age at reduced price March 23, 2016
• pCPA began negotiations price in May 2016
• Product monograph revision May 26 2020

10. HPP Challenges: In 2016 ERT approved only for pediatric –
onset HPP provided ERT begins before adulthood
• <2 dozen infants & children in Canada with HPP on ERT
• Adults with pediatric or adult onset HPP not approved for ERT on provincial
formularies
• Private insurers occ approve
• Compassionate access approved for ~8 adults BUT this is no longer an option
• Alexion Global Access to Medicine (GATM) program is now called a
“bridging program” but in Canada “bridge to nowhere” thus all
compassionate requests now denied
• Evidence poor for adults and cost very high
• diagnostic criteria and indications for ERT in adults under review by
expert consortium
• Recent new Phase 1 open label clinical trial of newer ERT enrolling
• Newer therapeutic options including gene therapy also on the horizon
• Need to address Real World Evidence (RWE) and how to incorporate into
decision-making
• New pricing models needed

11. GATM - Patient CANxxx
“I am sorry for both the decision and the
time it took us to reach it. To describe the
GATM program in a nutshell, GATM is a
bridging program designed to address the
pressing unmet medical needs that
patients with rare diseases face while we
work toward the development of long-
term, sustainable access solutions. At this
time, there is no likelihood that adult
patients with HPP (regardless of age on
disease onset) will ever gain reimbursed
access to asfotase alfa in Canada, unless
they started on treatment as a child.
Because of the lack of this “bridge,” the
patient had to be denied due to our Global
principles to the program.
Please note, should the reimbursement
situation change in Canada, we will
reconsider this case. We will also let you
know should a trial or other access
mechanism become available”.
• “Thank you so much for all that you
have done on my behalf. It's been a
rollercoaster of emotions. Not
knowing what was wrong with
me. Learning what was wrong with
me. Finding there was something
that would help me. Anticipating a
life of healing and the possibility of
less pain and less fractures. And
then not having access.
• I can't envision what the future will
look like for me and I almost wish I
didn't know it was HPP again, where I
still had some hope for getting
better. It's a mental game I guess.
• Thank again for your advocacy. I do
really appreciate your time and
care. I just need to get the tears out
and then maybe I can get my head
around things. ” Patient
GATM

12. The vast majority of data around patient exposure to interventions
occurs outside of traditional clinical trials
4
Copyright @2018 IQVIA, All Rights Reserved – Real World Evidence – An Industry Perspective 1
2

13. Outline
• From Clinical Trials to Access: One physician’s perspective
• Role of Physician Advocacy
• Overview of the approach to building capacity and providing precision
health to Canadians in the Prairies (MB and SK) with suspected
hereditary metabolic disorders (Inborn Errors of Metabolism)
• The Canadian Prairie Metabolic Network
•
CPMN OMICS First
Canadian Prairie Metabolic Network

14. Overall Challenges to Access to Therapies
•Need to make the diagnosis first!
• Pricing of Rare Disease Therapeutics*
• Inadequate understanding on part of “non-expert”
physicians, patients and public as well as “expert”
physicians about processes involved
• “expert” physicians need to be very involved in
patient education, discussion with provinces and
with pharma to ensure our patients get the most
effective treatment in the most cost effective way,
understanding most provinces deal with a cap.

16. Current Approach to Diagnosing IEMs
Challenges:
• Many IEMs
• Clinical features are often variable and non-specific
• Symptom onset occurs at wide range of ages
• Most IEMs are not screened for at birth
• NBS picks up most classical cases, but may miss patients
with milder mutations and subtle biochemical differences
Approach:
1. Biochemical testing
2. DNA testing
(Guerrero et al., 2018)

17. Our Local Situation as related to Metabolics
0
200
400
600
800
1000
1200
1400
1600
1990
1992
1994
1996
1998
2000
2002
2004
2006
2008
2010
2012
2014
2016
2018
2020
2022
Number
of
Appointments
Year
Metabolic Appointments by Year
• Increasing numbers
• Increasing wait times
• Dramatic advances in
genomic-based
technologies
• Increasing treatment
options
• Limited change in
staffing

18. “OMICS First” in Parallel with Traditional Approach

19. Hypothesis
Compared to the traditional approach for diagnosing IEMs, the “OMICS First”
approach (i.e., starting with comprehensive DNA testing) will lead to:
Improved timelines
Fewer/shorter
hospital stays
Improved diagnostic
yield
Fewer tests &
investigations
Same or lower cost
Same or better
quality of care

20. Cystic Fibrosis
(1982)
Single gene
testing
CAH
(1977)
Hemoglob.
(1973)
Hypothyroidism
(1973)
Full Genome
Sequencing
Exome
Sequencing
Diagnostic Testing: Where are we headed?
Metabolomics to Genomics
PKU
(1960)
Expanded
NB screening
(2000)
Gene panel
testing

21. For me being a researcher always came with
responsibility..
• Driven by what is in the best interests of patients and their
communities
• Advocate for patients with rare diseases and for communities facing
challenges because of their unique genetic identities
• Fair access, remove barriers to participation, know when to pull back
• Provide full information & full access to results with warmth & a
personal touch for families in crisis
• Empower communities - patients as full partners built on trust and
mutual respect

22. Thank you