The document discusses opportunities and challenges for personalized medicines and sickle cell disease treatments. It provides an overview of current limited treatment options for sickle cell disease and highlights several new treatment options currently under development or approval, including Novartis' crizanlizumab, Global Blood Therapeutics' voxelotor, and gene therapies. It notes obstacles to access like high drug costs, long review processes, Canada's drug pricing system, and the small market size. The presentation calls on stakeholders to work together to improve access and education.

1. Personalized Medicines: Access
Opportunities & Challenges
What is coming up for Sickle Cell Disease?
Biba Tinga, President/ED
Sickle Cell Disease Association of Canada/Association d’anémie
falciforme SCDAC

2. Who are we?

3. Limited Treatment Options: for over
40 years!
• Antibiotics
• Pain killers and anti-inflammatory
• Vaccines
• L-glutamine (Endari)
• Hydroxyurea
• Blood Transfusion
(High risks: Iron overload & reactions)
• Bone marrow transplant ( only cure available but not for
everyone – 10%)
It is only supportive care.

4. Hope is materializing!
New drugs are under development:
1 – Novartis: SEG 101 - Crizanlizumab is a
monthly infusion under development to
prevent VOCs, pain crises in patients with
sickle cell disease.
It is considered as a breakthrough therapy
because, it has the potential to prevent SCD
pain crises.
On Nov. 15,2019 -- FDA approves Adakveo!!!

5. A Patient wants a cure!
2. Global Blood Therapeutics, GBT has
developed a drug called voxelotor (GBT440). It
is an oral, once-daily therapy for sickle cell
disease. It increases the affinity of hemoglobin
for oxygen.
USA: as early as Feb. 2020
3. L-glutamine : under review by Health Canada

6. Gene Therapy: a universal cure?
3- Gene Therapy: availability in 2- 4 years?
Most patients are hoping for a cure thanks to
gene therapy.
CRISPR Therapeutics - Clustered Regularly
Interspaced Short palindromic repeats - a
replacement of a specific region of DNA
First patient in the US – 41 years old - Summer
2019

7. Gene Therapy as a solution
On Sept. 2019, Alabama – a 29 y. old man is free
of SCD after receiving gene therapy for 2
years – Bluebird Bio

8. What are the obstacles?
• Gene Therapy: 5 years monitoring before it is
classified as a cure and high cost
• Long review process: it can take up to 2 years for
Heath Canada to review a new drug safety.
• Canada Drug pricing: cutting the cost could impact
research, development, and future access (refuse to
enter the Canadian Market early on)
• Small number of patients do not make an
attractive market!

9. What can we do?
As patient group, SCDAC advocates for the best care
for the Sickle Cell Community. But we can do it
alone!
Mobilize, Organize, Unify and Educate!
• Educate patient population to participate in clinical trials
• Push for priority review process
• Engage key Partners: other rare disease groups ( CORD),
Industry Partners
• Make sure the government does not forget about us!

10. We will be ready!
• SCDAC/AAFC is currently working on a National
Registry for SCD
Collect data on patients diagnosed with SCD in
order to facilitate a wide variety of research
• Determine the disease prevalence
• Assess quality of life
• Improve standards of care
• Evaluate novel and existing therapies in real
world settings.

11. Core Ecosystem Element
Registry
Researchers
Industry
Clinicians
Health Care
System
Investigator
Network
Patient
Organizations
Government
Patients
Families
Caregivers
Courtesy of Dataffinity

12. A sickle Cell patient getting blood exchange

13. Thank you
Merci!

14. Canadian Organization for Rare Disorders
Access to Innovation Conference
Toronto, November 18-19, 2019
Personalized Healthcare:
Interactive Tools in Hemophilia
David Page
National Director of Health Policy
Canadian Hemophilia Society

15. Short bio
• Member, Canadian Bleeding Disorder Registry
Stakeholder Advisory Group (CBDR & MyCBDR)
• User, Web Accessible Population Pharmacokinetics
Service (WAPPS & MyWAPPS)
• Co-investigator, Patient Reported Outcomes, Burdens
and Experiences Study (PROBE & MyPROBE)

16. An Introduction to Hemophilia
• Genetic condition
• Deficiency in clotting
factors VIII and IX
• Frequent bleeding
into joints and
muscles
• Without treatment,
severe joint damage
and short life
expectancy

17. Severity and treatment
Severity / Factor level Symptoms Treatment
Severe
< 1% of normal clotting
activity
Frequent hemorrhages into
joints and muscles with no
trauma
2 to 3 IV infusions per week
of clotting factor to prevent
bleeding
(prophylaxis)
Moderate
1 to 5 % of normal
clotting activity
Less frequent hemorrhages
into joints and muscles
with minor trauma
IV infusions of clotting
factor to stop bleeding
(on-demand treatment)
Mild
5 to 40% of normal
clotting activity
Infrequent hemorrhages
into joints and muscles
after trauma
IV infusions of clotting
factor to stop bleeding
(on-demand treatment)

18. Prophylaxis and home care
• Young children learn to self-
infuse at home
• > 90% of clotting factor
concentrates are infused
outside hospital setting
• Ideally, patients go to the
hemophilia clinic only 1 or 2
times per year
How can care be best managed?

22. Pharmacokinetics (PK)
• Goal: > 1% of clotting
activity to prevent bleeding
• But every person has
different pharmacokinetics
(recovery, half-life)
So how to determine when
you are falling to the critical
1% level?

26. Desired medical outcomes
• Long-term survival
• Few or no bleeds
• Maintenance of joint
function
But if you ask Kevin …

27. Patient relevant outcomes
He wants to …
• be free of pain
• be able to play with his
friends
• be able to take part in
school activities
• avoid hospital and joint
surgery
• get a good education
• get a good job
• have a family

35. 3 connected apps
• The MyCBDR app allows patients to report their bleeds and
their infusions to their treatment centre in real time.
Treatment can be personalized.
• The MyWAPPS app allows patients to see their clotting factor
levels in real time. Activities can be adjusted accordingly.
• The MyPROBE app allows patient organizations to collect
and analyze patient relevant outcomes. These can be used
to advocate for improved care.

36. An introduction to ICER and the evolution
of the US landscape for drug pricing and
access (for high impact therapies)
Celia Segel
Director of Comparative
Effectiveness Research Policy
Development

37. © Institute for Clinical and Economic Review, 2018
Institute for Clinical and Economic Review (ICER)
• Independent health technology assessment group whose reviews are funded by
non-profit foundations
• Develop publicly available value assessment reports on medical tests,
treatments, and delivery system innovations
• Use cost-effectiveness analysis to determine value-based price benchmarks
• Convene regional independent appraisal committees for public hearings on
each report

38. © Institute for Clinical and Economic Review, 2018
Sources of Funding, 2019
2%
77%
8%
13%
Government grants and
contracts
Non-profit foundations
Contributions from health
plans and provider groups
Manufacturer grants and
contributions
ICER Policy Summit
and non-report activities

39. © Institute for Clinical and Economic Review, 2019
Valuing Cures: Key Conceptual Issues
Defining Cures: Broadening from cures to all “single and short-
term transformative therapies” (SSTs)
1. Uncertainty with unrecoverable costs
2. Additional domains of value
3. Time Divergence Between Costs and Benefits
4. Affordability and “Shared savings” in calculations of alternative
value-based price benchmarks

40. © Institute for Clinical and Economic Review, 2018
HTA and High Impact (Potentially Curative) Treatments
üCAR-T for B-cell Lymphoma
üZolgensma for spinal muscular atrophy
üEmicizumab for hemophilia A with inhibitors
ü[PCSK9 for high cholesterol]
Fair Price = Fair Access = Future Innovation

41. © Institute for Clinical and Economic Review, 2018
Patients, Caregivers and Advocates Input
• Understanding the patient population and subpopulations
• How to think about heterogeneity of patients with regards to treatment response/non-
response?
• Is there a sub-population that has particularly high severity?
• Understanding the standard of care: effectiveness and safety
• Understanding Outcomes:
• What are outcomes that matter to patients that are not captured in the trial data?
• How do patients find the outcomes captured in the trials meaningful to their quality of life?
• What are the limitations in the quality of life data used in our analysis and how should we
test it?
• What are important other benefits and contextual considerations for
understanding the treatment in our evaluation?
• Process with patients: Interviews, public comment periods (draft scope and
draft report), preliminary model presentation, external review, patient expertise
and testimony during a public meeting of appraisal committees

42. More Resources:
- ICER Final Methods for Cures
- ICER’s Valuing Cure Technical Brief
- ICER’s Patient Participation Guide

43. ///////////
HTA Case Study:
Larotrectinib for
TRK Fusion Cancer
CORD Conference
Nov 18, 2019
Brandon Levac, Senior
Manager – Patient Access
& Stakeholder Relations,
Oncology, Bayer Inc.
MAC-VIT-CA-0001-1

44. I am an employee of Bayer Inc.
Bayer has provided an unrestricted sponsorship to support this conference.
For complete information on Bayer products, please refer to the respective product monograph:
https://www.bayer.ca/omr/online/vitrakvi-pm-en.pdf
Disclaimers

45. VITRAKVI® (larotrectinib) is the first tumour agnostic treatment
approved by Health Canada
3
• Approved under NOC/c pathway on July 10, 2019
Indication
VITRAKVI is indicated for the treatment of adult and pediatric patients with solid tumours that:
• have a Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusion without a known acquired
resistance mutation,
• are metastatic or where surgical resection is likely to result in severe morbidity, and
• have no satisfactory treatment options.
Treatment with VITRAKVI should be initiated following confirmation of an NTRK gene fusion in a
tumour specimen using a validated test.
For complete prescribing information, please see the VITRAKVI Product Monograph: https://www.bayer.ca/omr/online/vitrakvi-pm-en.pdf

46. On Aug 29, 2019, a positive but limited initial pERC recommendation
for VITRAKVI was issued
Limited to Four Rare Tumour Types
Source: Larotrectinib pERC Initial Recommendation, accessed on Aug 29, 2019 at: https://www.cadth.ca/larotrectinib-neurotrophic-tyrosine-receptor-kinase-ntrk-locally-
advanced-or-metastatic-solid

47. Four rare tumour types recommended for coverage in initial pERC
recommendation, all others excluded
Adapted from Cocco et al. NTRK fusion-positive cancers and TRK
inhibitor therapy. Nat Rev Clin Oncol. 2018 (ePub ahead of print)
5

48. All stakeholder input either agreed with the initial recommendation, or supported broader coverage
Feedback on initial recommendation was provided by multiple
patient groups, clinicians, PAG and Bayer
6
Patient Groups Clinicians PAG Bayer
• Colorectal Cancer Canada
• Canadian Cancer Survivor
Network
• Patient group not stated
• Neuroblastoma Canada
• Cancer Care Ontario
• Cancer Care Ontario Skin DAC
• Clinical Medical Oncologist (9)
• Clinical Group – Lung Cancer
Canada
• Pediatric Oncology Group of
Ontario
• 2x Agree in part
• 2x Disagree
• 1x Agree
• 3x Agree in part
• Agree • Disagree
Source: Larotrectinib for Neurotrophic Tyrosine Receptor Kinase (NTRK) Locally Advanced or Metastatic Solid Tumours, CADTH website, https://www.cadth.ca/larotrectinib-
neurotrophic-tyrosine-receptor-kinase-ntrk-locally-advanced-or-metastatic-solid
Stakeholder Input

49. On Oct 31, 2019, a negative final pERC recommendation for
VITRAKVI was issued
No coverage recommended across all tumour types
Source: Larotrectinib pERC Initial Recommendation, available at:
https://www.cadth.ca/sites/default/files/pcodr/Reviews2019/10159LarotrectinibNTRK%2BSolidTumours_fnRec_REDACT_31Oct201_ChairApproved_final.pdf

50. Reflections and Recommendations for Improvement
8
• Larotrectinib is approved as a tumour agnostic treatment. pERC agreed it should be assessed as
such.
• The current review process does not support the assessment of novel, complex, rare disease
treatments. There is also a mismatch between evidence expectations and realities.
• Recommendations:
1. Increase scientific exchange during reviews between HTA bodies / submitter / expert
committees / clinicians / patient groups
2. When the HTA review identifies additional evidence needs, adopt conditional reimbursement
recommendations tied to reassessments
3. Partner on outcomes-based agreements and/or real world evidence generation to address
uncertainty at the HTA stage
4. Implement outcomes-based agreements at the pCPA/payer stage
5. Start now, decision makers can ask for volunteers to pilot

51. BRENT FRASER, VP PHARMACEUTICAL REVIEWS
NOVEMBER 18, 2019
Access to Innovation
Personalized Medicines: Access
Opportunities and Challenges

52. Conflict of Interest Declaration
• No conflicts of interest to declare.
• CADTH receives funding from Canada’s federal, provincial,
and territorial governments, with the exception of Quebec.
• CADTH is an independent, not-for-profit organization
responsible for providing Canada’s health care decision-
makers with objective evidence to help make informed
decisions about the optimal use of drugs, medical devices,
diagnostics, and procedures in our health care system.

53. Current Status
• Precision medicine (PM): customizing care based
on patients’ genetic factors
• Multiple examples where CADTH has provided
funding recommendations to treat condition with
specific genetic markers (e.g., oncology, rare dx)
• Do not follow a separate health technology
assessment process for PM

54. Challenges
• Uncertainty with respect to the role of the genetic
marker e.g., does its presence change the course
of treatment for patients?
• Trials may be for a smaller number of patients or
may be a subgroup within a larger trial.
• Trial designs may be “new” requiring addition
support, pre-work on methodology, etc prior to an
HTA review.

55. So What Needs to be in Place??
• Movement toward managed access agreements.
• This requires (for the most part) access to data.
• All actors across the system need to be aligned to
support a MAA approach to funding
recommendations.
• Implementation of reassessments – ranging from
simple to complex.
• Allows for expansion/contraction of the approved
patient population based on real value.

56. Life cycle HTA
Pre-market
dialogue
Managed entry
Post-market
surveillance Managed exit
Reassessment