1. CANADIAN ORGANIZATION FOR
RARE DISORDERS
Access to Drugs for Rare
Diseases in Canada

2. Canadians Suffer Without Orphan Drug Policy
 No definition, no orphan drug policy; few orphan
drugs.
 In 1970’s, only 10 new drugs approved worldwide for rare
diseases
 Orphan Drug Policies in USA (1983) and EU
(2000)
 In USA: about 425 approved drugs in 30 years since
Orphan Drug Act
 In EU: about 100 new approved orphan drugs in 13 years
 Benefit: estimates of up to 15 million people
 Canadian patients have NO access to half of these
drugs
 Canada has approved 47% of orphan drugs licensed in3/13/09Data Uncertainty/Rare Disorders
2

3. NEW Canadian Orphan Drug
Regulatory Framework
 OD designation criteria and processes aligned with US and EU
(promotes collaboration and simultaneous filing)
 Formal advice for clinical trials (Canada and/or international),
including design, sample, outcome measures, follow-up plan
 Transparency and information sharing throughout drug lifecycle,
available to HCPs, HTAs, and patients to inform decisions
 Life-cycle approach to accommodate evidence from multiple
sources before and after a drug is marketed
 Patient input: designation, CTs, approval, access, monitoring
 Approvals with required post-market monitoring and data
evaluation with mandatory reporting (≈5 years)
May 2010Access to Drugs Canada
3

4. Lifecycle Approach to Access for Orphan Drugs
• Similar scientific requirements (benefits, harms,
uncertainties); built-in flexibility for small clinical trials,
adaptive designs, surrogate markers, subgroup analyses
• Pre-Market: Pre-clinical/clinical data, quality, labelling;
designation; regulatory status elsewhere, evidence
limitations; post-market data collection plan
• Authorization: Require gathering and dissemination of
information to reduce uncertainties re: benefits/harms
• Post-Market: Reassess MA; require compiled information,
tests or studies; safety monitoring, label changes
May 2010
4

5. Evaluation Throughout Lifecycle
Drug Information Associationwww.diahome.org
5

6. Final decision made by Executive Officer
Drug Funding Process
Health Canada
Issues NOC & DIN
Interim decision made by Executive Officer
Non-CDR products /
non-pCODR products
Manufacturer submits
NOC= Notice of Compliance –
indicating drug is safe and effective
DIN= Drug Identification Number
CDR =Common Drug Review
CDEC = Canadian Drug Expert
Committee
pCODR = pan-Canadian Oncology
Drug Review
PERC = pCODR Expert Review
Committee
PCPA = panCanadian Pricing Alliance
Ontario’s CED reviews Health Canada status, CDR recommendation, pCODR
recommendation and PCPA; conducts Ontario-specific review
CED provides recommendation to Executive Officer to reimburse (or not) through
publicly funded program
Common Drug Review products
(NCE / new combination product /
new indication)
CDEC recommendation to drug plans
Manufacturer submits
pCODR Products
(NCE / new combination product /
new indication)
pERC recommendation to
drug plans
specific to oncology drugs
Up to 2 years
Non-transparent
Up to 1 year
Transparent
panCanadian Pricing Alliance Negotiations
Up to 2 mths
Transparent
~ varied; not
ntransparent
Open ended

7. Rare Disease Drugs: Challenges for Reimbursement
 Incremental Value Added (effectiveness, side effects, tolerability,
improved quality of life) may not equal incremental costs
 Pricing criteria may not be established, and willingness to pay may
have little impact on pricing
 Medicines for rare and unmet needs tend to have high R&D, high
uncertainty, high cost
 Reimbursement strategies may be directed toward reducing uncertainty
in safety, effectiveness, appropriate use, and budget impact.
 Managed access schemes include registries, CED, prior authorization,
limited use, $ capitation.
7

8. CDR Limits Access for Orphan Drugs
 CDR same as for common drugs
 RCTs = small samples, short timeframes, surrogate markers
 High $ development, small population = High $/patient
 Cost-utility: $/QALY below theoretical $50k threshold
 Small # = Low budget impact
 CDR recommends “no” to most drugs for rare disorders
 50% of common drugs = “Do not list”
 70% of DRD = “Do not list”
 20% of DRD = “list with conditions”
 5% of DRD = “yes”
 Provincial drug plans usually adopt CDR recommendations
 Private drugs plans usually cover (but some do not)
 EU varies but best = 80% to 100% funding
8

9. Access Mostly by Individual Approval
Drug Indication recommend Access
Replagal Fabry’s No 3 Yr Research
zavesca Gaucher’s No Individual
Fabrazyme Fabry’s No 3 Yr Research
Aldurazyme MPS I No Yes
somavert Acromegaly No Individual
Exjade Iron Overload Conditional Individual
Nexavar Kidney Cancer No Individual
Sutent (Renal) Kidney Cancer No Individual
Sutent (GSIT) GIST Conditional Individual
Myozyme Pompe’s Conditional Individual
Elaprase MPS II No Individual
Xyrem Narcolepsy No
Revlimid MDS JODR - No Individual
Catena Friedreich’s Ataxia Quebec Only
Soliris PNH No Individual
Naglazyme MPS VI Not Submitted Individual
Cayston Cystic Fibrosis Yes In Submission
Ilaris CAPS No Individual
Kuvan PKU NO Individual

10. Canadian Budget Impact Orphan Drugs
 Private Insurers
 Private insurers reimbursed $10.1 billion in drug costs in 2011
 Over 50% of all drugs are purchased privately in Canada
 High-cost, specialty drugs a growing challenge in the future
 Currently specialty drugs represent about 20% of plan costs for
employers, but less than 1% of total claims
 Specialty drug costs forecast to be 25% of cost by 2015 – 61% of
drugs in Phase III trials are specialty drugs
 Public Drug Plans
 Only 50%-60% OD have market approval in Canada
 OD accessed through Special Access Program mostly NOT
reimbursed by public drug plans
 Rare disease drugs less than 1% total public drug spend
Drug Information Associationwww.diahome.org
10

11. Provincial Drug Access for Rare Diseases
 2010: Ontario Drugs for Rare Diseases Program; uses
Markov Model to set “start-stop” criteria for gaining access,
staying on therapy, or stopping
 2010-11: BC Rare Disease Committee reviews on case-by-
case basis
 2011: Alberta establishes Special Authorization Process
including rare disease drugs; Start-Stop criteria; separate
fund for off-label drugs
 2011-2012: Ontario leads implementation of panCanadian
Pricing Alliance to negotiate single price for all; 1st drug for
rare disease
 Quebec: 2012 announces Rare Disease Plan (but no
action)
 NEW! April 2014: CADTH says no separate pathway for

12. Lifecycle Approach Sets Up
Managed Entry Programs
 Propose “coverage with evidence development” for
orphan drugs
 Early approval based on life-threatening or severely
debilitating condition with no other effective treatments
 Regulatory approval for ODs require on-going data
collection and resubmission of outcomes data (5 years)
 Patient registries to collect post-market safety and
effectiveness
 On-going studies with expanded patient population
 Challenge of “no funding” to expanded data collection
 Limits access to patients beyond clinical trials
 Limits “real world” data collection
Nov 2010USA CA EU Access to OD
12

13. Examples in Oncology
Evidence Building Program
 Principles for funding CTs within funded indication
 Equitable and timely access to treatments that are safe, offer
maximum clinical benefits, and align with best practices;
 Ensure coverage decisions are evidence-based, fiscally responsible,
and consistent with the OPDP policies
 Fair, transparent, and accountable process
 Examples of EBP Clinical Trials
 Change in dosing/schedule or combination with another agent
 Population not funded
 For re-treatment
 Approved indication but not “cost-effective”
 Indication under trial
 Same or different pharmacological class as funded drug
13NIHTA November 2013

14. Sustainable Access to Orphan Drugs
 Prices remain high because of lack of competition for small markets
(biosimilars not that easy); international pressure for:
 Value-based pricing assessed not at market entry but after period of
“real-world” use; consensus benchmarks and outcome indicators
(Need sufficient database and appropriate patient subgroups)
 Pricing transparency (actual negotiated prices, including rebates)
 Automatic price reduction at expiration of patent and market
exclusivity period
 Patented Medicines Pricing Review Board “ceiling price” not reality
 PMPRB: Starting point for price negotiation but CONFIDENTIAL
 panCanadian “Product Listing” Alliance: starting point for universal
pricing, listing, and re-evaluation/re-negotiation
 Compatible with Health Canada lifecycle model with evaluation plan
submitted at time of market authorization
Drug Information Associationwww.diahome.org
14

15. CORD ARCTIC QUEST—August 2011
What can people with rare disorders do?
Anything!

16. Thank You!
Nov 2010USA CA EU Access to OD
16
Durhane Wong-Rieger, PhD
President
Canadian Organization for Rare Disorders
www.raredisorders.ca
416-969-7435
durhane@sympatico.ca