Canada s Rare Disease Strategy: Pathway to Timely Sustainable Access CADTH Conference Durhane Wong-Rieger, PhD Canadian Organization for Rare Disorders President & CEO
Getting to Sustainable Access What is current status of access to drugs for rare diseases in Canada? What is desirable for patients, prescribers, payers, and producers? What are emerging international best practices? What are the opportunities with Health Canada, CADTH, pcpa, private and public payers? What are the obstacles? What is a sustainable and workable way forward for Canada? 2
Rare Diseases: Unaddressed Public Health Issue But Canada s federation makes national approach a challenge!
# Canadians with Common vs. Rare Diseases 3.5 Milions Affected 3 2.5 2 1.5 1.8 M 2.4 M 1.4 M 2.8 M Cancer Diabetes Heart disease Rare Diseases 1 0.5 0
5 Key Goals of Canada s Rare Disease Strategy 1. Improving early detection and prevention 2. Providing timely, equitable and evidence-informed care 3. Enhancing community support 4. Providing sustainable access to promising therapies 5. Promoting innovative research Canada Rare Disease Strategy Opportunities for Access Feb 2016
Rare Disease Strategy Supports Transforming Therapies into Improved Care Studies designed to promote understanding of effectiveness of interventions in real-world systems of care Range of therapies and health services as co-interventions, such as diet therapy, physiotherapy, family support and counseling, telehealth, and interdisciplinary team care, specialized treatment centers, and care coordination Identify long-term impacts of care, including potential adverse effects Determine how real patients and disease characteristics influences treatment effectiveness; account for clinical heterogeneity 6
7 Traditional HTA Limits Orphan Drug Access HTA OFTEN 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 HTA recommends no to most drugs for rare disorders Private drugs plans usually cover (but some do not) Public drug plans usually adopt HTA recommendations HTA limits access in some European countries Half of all orphan drugs evaluated have been rejected by one or more HTA bodies in the UK. Where Cost-Effectiveness NOT norm, reimbursement varies; best = 80% to 100% funding
Canadian (Limited) Access to Rare Disease Drugs Drug Indication recommend Access Replagal Fabry s DNL 3 Yr Research Zavesca Gaucher s DNL DNR/CBC Fabrazyme Fabry s DNL 3 Yr Research Aldurazyme MPS I DNL DNR/ON SP/CBC Somavert Acromegaly DNL DNR/CBC:ON Exjade Iron Overload LWC DNR/LWC AB BC/CBC ON) Nexavar Kidney Cancer DNL CBC Sutent (Renal) Kidney Cancer DNL CBC Sutent (GSIT) GIST LWC CBC Myozyme Pompe s LWC DNR/CBC Elaprase MPS II DNL DNR/CBC Xyrem Narcolepsy DNL DNR Revlimid Myelodysplastic Syndome JODR - DNL CBC DNL = Do not List; LWC/C = List with Criteria/Conditions; LSM List Similar Manner DNR = Do not Reimburse; CBC = ICase-by-case; SP = Special Program; UR = Under Review
Canadian (Limited) Access to Rare Disease Drugs Drug Indication recommend Access Soliris Paroxysmal Nocturnal Hemoglobinuria DNL DNR/LWC:ON/CBC:AB MB Naglazyme MPS VI Not Submitted CBC:ON Cayston Cystic Fibrosis LWC UR Ilaris Cryopyrin Associated Syndrome DNL DNR/CBC:ON Kuvan Phenyketonuria DNL DNR/SP:ON Volibris Pulmonary arterial hypertension LWC CBC/LWC:QC PEI Vimizim Morquio (MPS IV) DNL DNR Revolade Idiopathic pulmonary fibrosis DNL DNR (LWC:QC) Afinitor Tubersclerosis Complex - Renal DNL DNR/UR/SP:ON Afinitor Tubersclerosis Complex SEGA DNL DNR/UR Firazyr Hereditary Angeiodema LWC/C UR/LWC:QC Somatuline Acromegaly LSM LSM Juxtapid Homozygous Familial Hypercholesterolemia DNL DNR/UR DNL = Do not List; LWC/C = List with Criteria/Conditions; LSM List Similar Manner DNR = Do not Reimburse; CBC = ICase-by-case; SP = Special Program; UR = Under Review
Canadian Limited Access to Rare Disease Drugs Drug Indication recommend Access Opsumit Pulmonary arterial hypertension LWCC UR Mozobil Hematopoietic stem cell mobilizer DNL DNR/SP/LWC Zaxine Hepatic encephalopathy LWC/C LWC:QC/UR Adempas Thromboembolic pulmonary hypertsnsion LWC LWC Soliris Hemolytic uremic syndrome DNL DNR/UR Ofev Signifor Adcirca Elelyso Actemra Remodulin VPRIV Idiopathic pulmonary fibrosis LWC UR Cushing s Disease DNL DNR/UR Pulmonary arterial hypertension LSM DNR/UR Gaucher s Disease DNL UR Polyarticular juvenile idiopathic arthritis LWC LWR/UR Pulmonary arterial hypertension DNL DNR/CBC:ON Gaucher s Disease LWC DNR/SP:ON BC/UR DNL = Do not List; LWC/C = List with Criteria/Conditions; LSM List Similar Manner DNR = Do not Reimburse; CBC = Case-by-case; SP = Special Program; UR = Under Review
Int l HTA Limits Equity of Access Australia (PBAC) Canada (CADTH) England (NICE/AGNSS) France (HAS) Scotland (SMC) Kalydeco: cystic fibrosis with G551D mutation Recommend (March 2014) Restricted (March 2013) Funded NHS; review Clinical Priorities Advisory Group (2012) Recommed (Nov. 2012) Not recommend (Jan 2013); via Orphan Drug Fund Soliris: paroxysmal nocturnal hemoglobinu ria Not recommend (Mar 2009); eligible Life Savings Drug Program (2010) Not recommend (Feb. 2010) Not recommend (Feb. 2010) Recommend (Oct. 2007) Not recommend (July 2011) Elaprase: Hunter syndrome (MPS II) Not recommend (Nov. 2007); eligible Life Savings Drug Program (2012) Not recommend (Dec. 2007) (Not reviewed by NICE) Recommend (March 2007) Not recommend (July 2007) 11
Evidence about drug Balancing Timely Access and Certainty of Benefits/Risks We want certainty about safety and benefits of drugs We need timely access to drugs for unmet & urgent needs Time 12
Increasing Number of Patients Adaptive pathways Aim to provide timely access to new medicines by balancing medical need with evolving information on the benefit risk FULL APPROVAL Intensive monitoring of patients Additional indication(s) Intensive monitoring of patients Initial approval of niche indication Time 13
Key Obstacles MAPPs: perception that earlier access for (some) patients with limited data could lead to safety problems and undermine public trust More drugs for smaller patient subpopulations => not sustainable; unwillingness to pay for early access with limited data Need tools to limit access to approved subset (avoid off- label use) Practicalities and cost of implementing flexible or outcome based reimbursement strategies Extra work for regulators, HTA bodies, and payer due to repeat cycles of assessment and negotiations with sponsors Need capacity building and support for all stakeholders in order to fully integrate contribution of patients and patient organizations across drug life cycle
The real challenges seem to be more associated with efficacy than with safety Major reasons for late-stage failures (n = 73) Comment Efficacy (vs. placebo) 50% 50% Efficacy is the most frequent reason for failures in late-stage development This is not related to limited Safety (vs. placebo) Confirmation of early safety concerns Non classifiable 8% 23% 31% as 22 examples of top-10 pharmacos reveal Efficacy failures are largely influenced/ enhanced by Novelty of mechanism of action (MoA) Lack of differentiation Efficacy Safety 3% 16% 19% Objectivity of clinical trial endpoint Modality Novel MoA bears double failure risk Less objective endpoints (e.g. PROs) on average lead to ~10% increased failure risk 15
Lifecycle Approach with Patient Input & Post-Market/Real World Data Payer: Budget Impact; Access Criteria; R-W Data Collection Researcher/Clini cian: Disease Knowledge; Drug Discovery; Treatment Guidelines Patient Input HTA: Comparison Benefits, Risks, Cost w/alternatives; Place in Therapy Company: Clinical Trials & Outcome Measures; biomedical, clinical, PROs, Real-World Impact Regulator: Approval on Benefits-Risks- Uncertainties; Use & Real- World Monitoring 16
17 Thank You! Durhane Wong-Rieger, PhD President Canadian Organization for Rare Disorders www.raredisorders.ca 416-969-7435 durhane@sympatico.ca