Rosalie Wyonch, CD Howe Slides & David Page, Canadian Hemophilia Society Slides

1. Create Innovative Financing Pathways for
Efficient, Effective, and Cost-Effective Drug Access
Rosalie Wyonch
Senior Policy Analyst, C.D. Howe Institute
CORD Fall Conference
December 2, 2021

2. The C.D. Howe Institute is a registered charity, and an independent not-
for-profit research institute whose mission is to raise living standards by
fostering economically sound public policies. Widely considered to be
Canada's most influential think tank, the Institute is a source of trusted
policy intelligence, distinguished by research that is nonpartisan,
evidence-based and subject to definitive expert review.
The C.D. Howe Institute
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3. Discussion Points
1. Establish national agency to develop multiple financing pathways specific
to needs of patient population and drug characteristics for universal
access across multiple payers
2. Leverage Managed Access Programs to provide timely access of
approved therapies with potential benefits to specified patients under
conditions of continued monitoring and collection of real-world data.
3. Facilitate concurrent Health Canada and health technology assessment
reviews to promote shared interpretation of safety and efficacy data and
expedite access.
4. Implement processes for real-world data collection and utilization of real-
world evidence throughout drug cycle from clinical trials to real-world
usage to promote timely, evolving, evidence-informed access.
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4. Reflections on the Current
Health Policy Landscape
• The Canadian Drug Agency has the potential to address some of the issues with the panCanadian
Pharmaceutical Alliance, CADTH, INESS, all having a role to play. How does the PMPRB fit into the future
of Canadian pharma policy? As a quasi-judicial body with no comparator internationally, it is reasonable to
question what it’s role will and should be in the future.
• COVID-19 and the experience with vaccine access has brought the issues of timely access to medical
innovation to a level of priority and public awareness
• Balancing spending sustainability with access will require deep understanding of the complexity underlying the
market, not simply aggregate spending and prices. Unintended consequences must be considered – the unique
challenges related to orphan and rare disease treatments will likely require further cooperation between
government departments (ISED, Health Canada), research institutions and industry investment.
• The current impasse between government, pharma companies, and payors benefits no one, especially
patients. The Rare Disease Strategy and recent COVID-19 experience might lead to a more beneficial
path…. But government and industry must cooperate, both benefit when innovative treatments get to
patients.
• Certainty and Transparency in pricing evaluation and policy will be critical for the future of the
lifesciences industry in Canada.
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5. COVID-19: Changing Narratives on Value
• Health system weaknesses illuminated, limited resources
but high expectations for improvement
• Opportunity:
Changing narratives on prices and access – value
incorporates stability/resiliency, in addition to price and
patient outcomes.
• Challenge:
Tyranny of the urgent – staff shortages, expansions in
LTC, improving hospital and digital infrastructure.
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6. Healthcare investments: Past and Future
• If healthcare spending were to continue to grow relative to GDP at a
similar rate to the past 20 years, it would increase from about 11.5
percent of GDP in 2019 to 14.6 percent in 2040 – about 3.1 percent.
– An estimate factoring in the increased costs of upgrading and
expanding infrastructure, increasing staffing levels and the
aging population projects that spending on institutional care
alone would increase to 4.2 percent of GDP by 2041, from 1.26
percent in 2018.
• According to the Canadian Medical Association, about $2.3 billion
(~1%) of annual health spending could be better spent (Simpson,
2014). The OECD estimates that internationally, about 20 percent of
health spending is directed to activities that do not add value
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7. VBHC in Canada
Social Impact
Bonds
A non-profit service provider seeks private investment to finance a social
program. The government repays investors with interest if the program
meets targeted outcomes.
Outcome-linked
funding
The amount that a health service provider receives depends on the extent to
which predefined outcomes measures are achieved.
Accountable
Care
incentive payments reward healthcare providers that deliver higher quality
care using a variety of process, patient experience, and/or outcome metrics
over time.
Bundled
Funding
payments for specific procedures or integrated funding for groups of
patients are designed to cross traditional organizational and/or budget silos.
Outcome-linked
procurement
the amount of money that a supplier receives depends on the extent to
which predefined outcomes are achieved
Open
Innovation
Challenges
Open innovation challenges specify a desired outcome and reward
innovators who best meet it, rather than a traditional funding or
procurement approach that selects those who will be supported and
specifies how a goal is to be achieved.
Source: CFHI Value-based Healthcare Toolkit (https://www.cfhi-fcass.ca/docs/default-
source/itr/tools-and-resources/vbhc/vbhc-toolkit-e.pdf )
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8. VBHC Examples
8
Payment Reform
(jurisdiction)
Sectors Included Population, Time interval, Target Outcome
Accountable Care
(Saskatchewan)
Hospitals (in-patient) In-patients: improved clinical outcomes, patient flow, patient satisfaction
Hospital staff and care provider satisfaction, retention and recruitment.
Open Innovation
Challenges (Canada)
All health care sectors,
companies of all sizes,
research groups, students,
and others.
Between 2011 and 2016, there were 10 ImagineNation Challenges with a
combined total of $2.3 million in awards. They involved 435 team or
individual submissions from across Canada, as well as 211 volunteer
judges
Social Impact Bond
(Toronto, Vancouver)
Community/Pharmacy Enroll 7,000 Canadians aged 60 or older with pre-hypertension in a six-
month program to help them adopt healthy behaviours and control their
blood pressure
Outcome Linked
Funding (Ontario,
British Columbia,
Quebec, Prince Edward
Island, and
Newfoundland and
Labrador)
Jurisdictions; health regions,
disease-specific
associations, health
association with the support
of the jurisdiction; or others
with prior agreement of
Canada Health Infoway
Projects in 5 jurisdictions (Ontario, British Columbia, Quebec, Prince
Edward Island, and Newfoundland and Labrador), mostly focused on
patients with congestive heart failure or chronic obstructive pulmonary
disease.
Outcomes measures include recruitment, retention and at least two health
outcome measures, such as reductions in emergency department visits
and hospital readmissions.
Bundled Funding
(Ontario)
Hospitals, physicians,
homecare and rehabilitation
services.
Under bundled or integrated payment models, a group of healthcare
providers receives a pre-determined payment to cover all the services
required for an episode of care. The intention is to align incentives to
improve quality and the patient experience while controlling costs.
Outcome Linked
Procurement (New
Brunswick)
Ambulance services, Home
care (extra-mural program)
and 811 teletriage health
advice line.
Payment under the 10-year $74 million incentive-based contract depends
on results for 15 pre-defined indicators. Examples include reducing
emergency department visits and hospitalizations, increasing the number
of home care visits, having less variation in home care programs, and

9. Pharmaceutical Coverage and Spending:
Collaborative Cost Containment
• Budget Impact and Managed Entry Agreements:
• Manages real-world effectiveness and market size uncertainty
• Initial prices can be adjusted as more evidence becomes available, following
market launch.
• A case study of managed-entry agreements in four countries (Belgium, the UK,
the Netherlands and Sweden) found well over 100 such contracts. Their exact
form varied:
– some of the price adjustments were conditional on total expenditure,
– others provided for systematic collection of patient outcome data post-launch, or
monitoring the restrictions on the patient categories for which the drug was prescribed
(Ferrario and Kanavos 2015).
– Some agreements were described as having “payment by results,” where the drug price
paid depends on observed patient outcomes.
• See Blomqvist and Wyonch 2019 for further international comparisons and
discussion of pharmaceutical cost containment strategies and regulations.
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10. Thank you!

11. CORD Fall 2021 Conference
Meaningful Patient Engagement
Advocating for Access to a Novel Therapy
for Hemophilia A:
Success or Failure?
David Page
National Director of Health Policy
Canadian Hemophilia Society

12. Research Support None
Director, Officer, Employee Canadian Hemophilia Society
Shareholder None
Honoraria None
Advisory Committees (last 3
years)
Roche, Novo Nordisk, CBS, Héma-Québec
Consultant None
Personal health benefit No
Bias
Yes, I have many friends and colleagues with
hemophilia A who would benefit. I am biased.
Disclosures

13. This will be the story of efforts by the Canadian
Hemophilia Society between 2018 and today to obtain
access to an innovative therapy (emicizumab or
HemlibraÒ) for Canadians with hemophilia A

14. What is hemophilia A?
• Genetic disorder
• 1 in 8,000 births
• A deficiency in the factor VIII
protein
• Internal bleeding, especially
into joints
• Severe forms are usually fatal
by the age of 20 if not treated
• 75% of people in the world are
not treated

15. Time Product Active ingredient
1950-1965 Fresh frozen plasma Human factor VIII
1965-1975 Cryoprecipitate Human factor VIII
1975-
Plasma-derived factor
VIII concentrate
Human factor VIII
1992-
Recombinant factor VIII
concentrate
Recombinant human factor VIII
2018- Emicizumab
Bispecific monoclonal antibody
that mimics factor VIII
2023- Many
Other MABs, RNAi, anti-TFPIs,
serine protease inhibitors, gene
therapy …

16. Emicizumab Factor VIII
Half-life 28 days 12 hours
Administration
Sub-cutaneous, once a week Intravenous 2 to 7 times per week
Neutralizing anti-drug
antibodies
in 0.1 to 1% of cases 30% of babies
Efficacy
Steady-state equivalent to 15% FVIII
level
High peaks and low troughs: 1%
before the subsequent infusion
Equally efficacious for those with a FVIII
inhibitor
Not efficacious for those with a FVIII
inhibitor
Less bleeding into joints
Long-term joint damage despite
FVIII prophylaxis

17. Plasma protein products and
their alternatives
Other drugs
Quebec Rest of Canada Quebec Rest of Canada
Health
technology
assessment
INESSS/CCNMT CADTH/CBS INESSS CADTH
Decision on
reimbursement
Quebec MSSS
P/T Council of
Deputy
Ministers (9+3)
Quebec MSSS Individual P/Ts
Procurement,
distribution to
hospitals
Héma-Québec
Canadian Blood
Services
Each P/T
Plasma Protein Product (and alternatives) Review Process

18. Advocacy effort # 1 (before NoC):
Convince Quebec and the other P/Ts that emicizumab should
be reviewed as a plasma protein product (or alternative) for
CBS/H-Q formularies
• Substitute for factor VIII
• Biological drug like factor VIII
• Same function in coagulation as factor VIII
• Prescribed by hematologists like factor VIII
• As an expensive treatment for a rare disease, same need for national
procurement and pharmacovigilance

19. Emicizumab regulatory approval
August 2018* Hemophilia A and inhibitors** to factor VIII
June 2019* Hemophilia A without inhibitors to factor VIII
*Timing consistent with approvals by FDA, EMA
** Inhibitors affect 30% of babies with severe hemophilia A patients. The
immune system eliminates the infused factor VIII in minutes. Much more
expensive, less efficacious treatments are required.

20. Advocacy effort # 2:
Access for those with an inhibitor

21. CHS submissions to the HTA agencies: inhibitors
• Research data on reduced bleeding
compared to alternatives
• Written and video testimonials from
parents of children in clinical trials
• Detailed comparison by CHS of cost of
emicizumab vs. current treatments
(savings of $3,000,000 per month)
• References to international HTA reports
(e.g. ICER)

22. CHS advocacy efforts: June 2018 – May 2019
• Letters to, meetings with health officials in all provinces
• Frequent communications with manufacturer and blood
services (CBS and Héma-Québec) … but …
• No decision for 9 months … (at a cost of $27,000,000 to the
health system)
And then …

24. Coincidence?
May 5, 2019 Media coverage
May 9, 2019
Decision in Quebec to fund
emicizumab for all patients with
inhibitors
May 31, 2019 Decision in the rest of Canada to
fund emicizumab for all patients
with inhibitors

25. Advocacy effort # 3: Access for those without an
inhibitor…
• Health benefits not as dramatic
• 1000 people vs. only 100 with inhibitors
• Perception (!?!?) of a large budget impact

26. HTA processes
INESSS:
July – December 2019
July – December 2020
CADTH
July – December 2020
Meanwhile, emicizumab became a standard of care in
the U.S., Europe, Japan, Australia …

28. CHS survey of people’s lived experience
• On-line survey, based on CADTH/INESSS patient submission
template
• Results (quantitative and qualitative) showed:
• High physical, psychosocial and socioeconomic burden of disease
• High burden of treatment
• Impact on the entire family

29. Canadian data from PROBE (Patient Reported Outcomes, Burdens and Experiences) study
Severe hemophilia A
No bleeding
disorder (controls)
Use of mobility devices in last 12 months 51/181 (28%) 7/107 (7%)
Difficulties with activities of daily living 51/181 (28%) 13/107 (13%)
Use of pain medication 128/181 (71%) 53/107 (49%)
Working full-time or part-time (ages 22-64) 98/151 (68%) 70/87 (80%)
Retired, unemployed or long-term disability (ages
22-64)
40/151 (26%) 11/87 (13%)

30. INESSS recommendation # 1:
Emicizumab should not be added to the Héma-Quebec
formulary
• “Factor VIII is already safe and effective”
• “Emicizumab: lack of evidence of non-inferiority”
• ‘Study size too small”
• “Uncertainty concerning anti-drug antibodies”
• “More data needed”
N.B. The patient perspective appeared to be entirely
discounted in the decision document.

31. INESSS recommendation # 2:
Emicizumab should not be added to the Héma-Québec
formulary
• “Weak methodology in studies”
• “Numerous biases”
• “No relevant comparator”
• “Concerns over post-marketing pharmacovigilance”
• “Short follow-up”
• “Promise of improvement not supported by high-quality
data”

32. CADTH HTA recommendation: December 2020
Yes, grant access … but
ü “Only for people with severe disease”
ü “Only under the care of a hemophilia specialist”
v “Only if less costly than the least costly FVIII”

33. Budget impact
CHS did a full economic analysis of the hemophilia A market
in Canada using publicly available data on pricing and
utilization.
Conclusion: At a cost of X, emicizumab could be introduced
with no budget impact compared to current costs.
This analysis was shared with CBS and the payers to
counteract perceptions stemming from the CADTH report.

34. Member letter-writing campaign to Ministers of
Health and local members of the legislatures
10,000 letters sent in first month!

35. CHS advocacy efforts
• Collaboration with hemophilia doctors to critique flawed
methodology in INESSS report
• Hemophilia doctors’ letter to Quebec Minister of Health in
support of access
• Newspaper and television stories in multiple provinces
• Sending latest research (including non-drug costs and
savings)
• Behind-the-scenes advocacy with …
• Quebec hematologists
• Quebec Ministry of Health
• Political staff of Minister of Health

36. Quebec results (August 2021): 95% failure
• The MSSS overruled INESSS and added Hemlibra to the
H-Q formulary … and decided that it is …
üNot “interchangeable” with factor VIII for children 4
years and less (only 5% of severe patients)
but …
v“Interchangeable” with FVIII for those 5 years and up,
meaning it must be sent to a future tender (appel
d’offres) in direct price competition with FVIII

37. Rest-of-Canada results (September 2021): 95% success
• The P/Ts added emicizumab to the CBS formulary…
ü For those with less than 1% FVIII (95% of severe cases), no
other conditions
• Transitions started on October 18
• 20-30 new patients per month

38. Why does Canada take so long?
• Issues specific to this case
• Perception that “hemophilia has been solved”
• Perception of high budget impact
• General issues
• Built-in delays in adopting innovative technologies
• HTA bodies’ methodological bias in reviewing drugs for rare
diseases
• Secrecy in pricing makes cost/benefit analyses opaque or just
wrong (“garbage in, garbage out”)
• Discounting of patient perspective

39. Best practices in patient advocacy
• Patients and physicians: have a clear position and a unified
voice
• Inform and involve your members
• Gather your own data on “lived experience”
• Present the most relevant research
• Discover, analyze and compare the costs (follow the money!)
• Combine data and anecdote
• Don’t give up!

40. Documentation in English and French
• HTA reports and CHS patient submissions
• CHS letters to Ministers of Health
• Physician letters to Ministers of Health
• Webinar on Hemlibra for members
• Q&A about Hemlibra
• Sample letters to politicians
• Communiqués
• https://www.hemophilia.ca/hemlibra-access/
• https://www.hemophilia.ca/fr/hemlibra/