1. Managed Access Programs:
Timely, Appropriate, Sustainable Access
for Rare Disease Drugs
Durhane Wong-Rieger
March 5, 2015
Enlightened New Direction or
Déja-Vu All Over Again?

2. Panel: Waiting for Access
 Personal story
 Name, diagnosis
 Brief history: symptoms, impact on life and quality of life,
treatments received, result, unmet need
 Hope/expectations of new therapy
 Managed Access Approach
 Who should get access?
 What would indicate it works?
 What if it doesn’t work?

3. (Sep 2004): Task Force on National
Pharmaceutical Strategy
 First Ministers direct Health Ministers to establish Task Force to develop
and implement National Pharmaceuticals Strategy
 Task Force (led by BC) agreed on nine elements
 Catastrophic coverage
 National Drug Formulary
 Breakthrough drugs approval
 Real-world drug safety and effectiveness
 Purchasing strategies for best prices
 Prescribing behaviours to appropriate use
 Electronic Health Records,
 Access and parity pricing of non-patented drugs
 Drug plan policies (best practices)

4. When Does HTA (CDR) Disadvantage
Patients?
 When new (breakthrough) treatments are much more
expensive than older treatments
 When new therapy has no comparator (first treatment)
 When therapies (for serious, life-threatening) conditions
are approved with less definitive outcomes (surrogate,
short-term measures)
 When patient population is small (rare disorders,
children, subtypes) so outcomes are less robust
 When outcomes difficult to quantify or measure
objectively or relationship between short-term surrogate
measures and long-term outcomes unclear.

5. (2006) NPS Priority: Expensive Drugs for
Rare Diseases
 Objective: Consistent national processes and standards to
ensure access to appropriate and affordable treatments
 Special consideration of EDRDs determining when, or under
what conditions … to publicly reimburse therapies that do
not meet common standards of evidence
 Aspects of EDRD policy: international risk/benefit
assessment, appropriate access, evaluation appropriate to
rare diseases, sustainability of funding, monitoring and
evaluation, ethical considerations and public input into
decision-making

6. (2006): NPS Recommendations for
TASK FORCE ON EDRDs
 Assess international approaches
 Engage stakeholders
 Small group of experts to identify short, medium, and long-term
strategies for rare diseases and other breakthrough treatments
 Achieve meaningful exchange on the societal choices in
determining access to and payment for EDRDs
 Accelerate framework drawing on expertise from government,
research community, patients, and providers:
 Develop approaches to evidence and ethics
 Identify means to align regulatory and reimbursement decision-
making

7. (2010): CMAJ Alternative Policies for
Rare Diseases
 Canada lacks a policy framework for drugs for treating rare
diseases, but it can learn from other countries.
 A population proportion threshold is needed to define rare
diseases in Canada, and patient registries can be used to track
the progression of disease and related effects.
 Legislation is needed to incent drug development and reimburse
patients for costs of drugs for rare diseases.
 An alternative approach to economic evaluation should be
grounded in the rule of rescue.
 The framework must be a federal imperative and funded
appropriately

8. (30 Sep 2014): Health Ministers’ Press
Release: Orphan drugs for rare diseases
 Orphan drugs are used to treat life-threatening, chronic
and seriously debilitating rare diseases
 … And are very costly
 Growth rates for orphan drug market expected to double
overall prescription drug market by 2018
 Establish a working group led by Alberta, British Columbia
and Ontario on how to manage the cost of rare disease
drug therapies with evidence-based approaches.

9. CORD Response to Health Ministers’
Orphan Drugs Announcement
 Need for bold decisive action
 Federal government has introduced “state-of-the art” Orphan
Drug Regulatory Framework based on international best practices
 PT Health Ministers position: revisioning 2006 NPS
 Working Group should build on current practices: managed
entry/exit criteria, coverage with evidence building, and risk-sharing
 Ontario Drugs for Rare Diseases
 Cancer Care Ontario Evidence Building Programs
 Personalized (targeted) therapies
 Re-focus: Saving lives and reducing disabilities rather than just short-
term costs
 Goal: provide access as soon as possible to reduce deaths and
disabillities

10. Facts re Affordability of Orphan Drugs
and Rare Diseases
 Drugs for rare diseases affordable within the public drug plans
 Account for less than 1% of all drug plan budget
 In European countries with the best access, orphan drugs still
cost only 2.5% to 3.5% of the drug budget.
 Public health system save money by providing patients with right
drug as soon as possible
 Costs in long-term disability and care to NOT treat patients
appropriately
 Almost all healthcare, including diagnosis, doctor care,
emergency care, hospitalization, rehabilitation, and supportive
care are expensive for rare diseases, mostly because these are
mostly severe and life-threatening diseases.

11. Managed Access: Proven Strategy for Orphan
Drugs
 Accommodate high uncertainty in safety and
effectiveness with on-going monitoring and data
collection through patient registries
 Address budget impact of uncertainty of patient numbers
(diagnosis, eligibility) through risk-sharing plans
 Collect cost-effectiveness data to address uncertainty of
long-term benefit vs. harms and health outcomes (QoL,
survival)
 Assure high cost of individual use and total budget impact
are justifiable in terms of appropriate patient use,
adherence, documented patient outcomes, and new
knowledge about disease

12. Learning from Cancer Care Ontario
Oncology Evidence Building Program
 Principles for funding Clinical Trials 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 Evidence-Building Program 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

13. CORD’s ASK for Orphan Drug Access
Strategy
 Rare disease patient community has taken the lead to provide
effective, affordable solutions. We have brought the best
international solutions to the table, Including
managed access programmes.
 We cannot afford NOT to treat patients with available therapies
while we are searching for the best solutions. We cannot afford to
keep patients waiting while the public system negotiates a price
with the company.
 Treat the patients first; adjust the price later. Adopt best practices
of countries like Germany, the UK, France, Italy, and Belgium.
 Health Ministers MUST act decisively and implement a
panCanadian access programme for rare diseases NOW.
2004 TO 2014 TO 2024?
10 YEARS FROM NOW … SAME RESPONSE AS 10 YEARS AGO?

14. Learning from (Italy) MAS for Orphan Drugs
Drug Name Therapeutic Indication Criteria on which MEA
is based
Vidaza®
(azacitidine)
Myelodysplastic syndromes 11% discount for the first 3
cycles of treatment
Sprycel®
(dasatinib)
Acute lymphoblastic & chronic
lymphocytic leukaemia
50% discount for the first 3
cycles of treatment
Tasigna®
(milotinib)
New Philadelphia
Chromosome + chronic
myelogenous leukemia
50% discount for the first 3
cycles of treatment
Nexavar®
(sorafenib)
Renal cell carcinoma 50% discount for the first 3
cycles of treatment
Revlimid®
(lenalidomide)
Multiple myeloma 50% discount for the first 2
cycles of treatment
Arzerra®
(ofatumumab)
Chronic lymphocytic leukaemia 50% discount for whole
treatment (12 cycles)

15. Learning from Ontario DRDs
Drug Name Therapeutic Indication Criteria for Access (Start-Stop)
Aldurazyme®
(laronidase)
Mucopolysaccharidosis
type I
Hurler-Scheie: Start if mutation + 1 clinical
(sleep, respiratory, cardiac, joint). Continue if
stabilized; Hurler pre HSCT only; Exclude Scheie
Elaprase
(idursulfase)
Mucopolysaccharidosis
type II
Start if 6 yrs+; no neurocognitive impairment; no
ventilation; Continue if no neurocognitive or
ventilation
Ilaris®
(canakinumab)
Cryopyrin-associated
periodic syndrome
Muckle-Wells: Start if NLRP3 mutation + SAA ≥
10; NOMID: Start if NLRP3 mutation + symptoms
@< 6 mos Continue if SAA < 10 + no disease
activity; Exclude Familial Cold Auto-
Inflammatory
Myozyme®
(alglucosidase)
Infantile/Early Onset
Pompe Disease
Start if diagnosis < 1 yr + symptoms +
cardiomyopathy. Continue no decline or cardiac
Myozyme®
(alglucosidase)
Adult/Late onset
Pompé disease
Start if serious muscular/respiratory symptoms +
no ventilation. Continue stabilize + no ventilation
Zavesca®
(miglustat)
Niemann Pick type C Start if mutation + Functional Disability ≥ 5 and ≤
10. Continue Functional Disability ≤ 10

16. Recommendations for
panCanadian Drug Access
 Performance-based Managed Access Schemes
 Key success factors
 Programs are national and international in scope
 Criteria (for start-stop) are evidence-based
 Drug prescribed only under supervision of qualified expert
 Guidelines flexible for individualized patient-centred access
 Patients, families and patient groups participate in
development and implementation of MAPs
 Support patients who do not respond to therapy to transition
to something else
 Companies participate in risk-sharing of costs
 Analyze drug performance over time to update guidelines

17. Thank You!
For more information:
Durhane Wong-Rieger
Canadian Organization for Rare Disorders
durhane@sympatico.ca
www.raredisorders.ca
Thank you!