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Market Access for Orphan Drugs: A Payer Perspective in Seven Countries Asher Lisec April 15, 2016 1 Orphan Drugs Treat Rare Diseases United States • “A disorder or condition that affects less than 200,000 persons” • 7.5 per 10,000 people European Union • “Occur so infrequently that the cost of developing a medicinal product to treat the condition would not be recovered by the expected sales of the medicinal product” • 5 per 10,000 people Australia • “A disease, or condition, likely to affect not more than 2,000 individuals in Australia at any time.” • 1.2 per 10,000 people Increases Orphan Drug Regulatory Approvals Approvals 2015: 42 Approvals 1973-1983: 10 Market Access Individuals are financially and physically able to obtain pharmaceutical product No comparator Small patient population Development Standard ICER not met Regulatory Approval Reimbursement Approval Patient Access No standard clinical guidelines Label Expansion Specific Aims Describe the payer policies that affect orphan drug market access Determine the factors that influence payer decisions on orphan drugs Describe the market access decisions payers can make in regards to orphan drugs Qualitative Key Informant Interviews with Payers Country Respondents Interviewed AU Health economics professor and HTA advisor to Medical Services Advisory Committee (MSAC) and Pharmaceutical Benefits Advisory Committee (PBAC) FR Health economics professor and advisor to Haute Autorité de Santé (HAS) and working group on economic evaluation of rare diseases DE Health economics professor and member of arbitration board for drug pricing IT Health economics professor and regional HTA advisor, member of committee for modernization of highcost medicines ES Health economics professor, regional HTA advisor, member of committee for modernization of high-cost medicines UK Health economics professor and HTA advisor to Scottish Medicines Consortium (SMC) and National Institute for Health and Care Excellence (NICE) US Medical director for national health plan – 11 million lives Medical director for integrated health plan – 1.1 million lives Pharmacy director for national Pharmacy Benefit Management (PBM) – 35 million lives Courtesy of RTI-HS Key Informant Interview Themes • Submission and Review Process • Four questions • Factors that Influence Payer Decisions • Four questions • Post-Market Requirements • Two questions • Payer Perceptions • Three questions Conducted by RTI Health Solutions Peer Reviewed Literature Search Results 411 294 117 •Results found in the US and European literature • Excluded after reading the abstract • Reasons: cost-effectiveness model (30%), no orphan drug results (23%), not target country (21%), out of date (8%), not in English (7%), duplicate (5%) •Papers met the criteria and were reviewed Themes from Peer Reviewed Literature • Market access decision methodologies in Europe and Australia • Variables that affect price • Variables that affect favorable market recommendation • Variation in approval rates between EU countries • • • • Payer perspectives Orphan drug market projections Post-market requirements Orphan drug market access policies • Pre-market barriers • Pre-market facilitators Grey Literature Search Results 16,599 2,806 1,445 •Results returned with initial search criteria •Included industry reports, CEO interviews, trade journals, white papers, commentary, and news • Dates restricted to 2015-2016 •Excluded peer reviewed literature •Excluded NASDAQ reports •Restricted location to US, Europe, and Australia Themes from Grey Literature • Orphan drug market forecasts • Pipeline • Approvals • Spending • US payer landscape • Perceptions of orphan drugs • Specialty and orphan drug budget trends • Policy and regulation • Pharmaceutical Market • Company profiles • Country specific healthcare and pharmaceutical reports Synthesis PEER REVIEWED Orphan drug market access policies Market access decision methodologies in Europe and Australia Post-market requirements Interview and Literature Review Themes INTERVIEWS GREY LITERATURE Submission and Review Process Policy and regulation Factors that Influence Payer Decisions US payer landscape Post-Market Requirements Orphan drug market forecasts Payer perspectives Orphan drug market projections Payer Perceptions Pharmaceutical market Process Submission and Review for Reimbursement No Country or Payer Policies/Procedures Specific to Orphan Drugs Submission Requirements • United States Varies by payer • Europe Review Timeline • United States 2/3 payers review on regular cycle • Europe Germany- Reduced dossier for drugs with Statistically significant differences budget impact < 50 Million between countries France- Cost-effectiveness model not required for budget impact < 20 Million • Australia Rule of Rescue • Australia Study found no difference between orphan and non-orphan drug review times Factors Interviews Associated with Payer Decisions United States EU / Australia • Data demonstrating clinical • Data demonstrating clinical benefit Literature benefit • Unmet need • Unmet need • Treatment sequencing • Cost Correlated with Decision in EU Not Correlated with Decision in EU & US • Alternative treatment (-) • Standard cost-effectiveness • Oral formulation (-) • Low overall budget (+) • Number of indications (+) • Study found 80% of US payers not using CEA • Median ICER in EU = 40,242 Understanding clinical benefit is one of the biggest challenges What is your biggest challenge in reviewing orphan drugs? AU FR DE Limited clinical evidence/ including comparative efficacy benefits & unmet need ● ● ● Cost/CE, and trade-off between CE and orphan drug objectives ● IT ● ES UK US ● ● ● ● ● Uncertainty in treatment sequencing ● Pressure from advocacy groups ● Differentiating real orphan/ ultra-orphan indications ● ● CE = cost-effectiveness Courtesy of RTI-HS Evidence To Bridge Gap When No RCT CLINICAL EVIDENCE GUIDELINES • Conduct post-marketing/real-world validation- US • Develop clear guidelines- US • Include start and stop rules for the new drug- US • Demonstrate clear survival improvements – ES, US, UK • Extend RCT with real-world study to extend time points for benefit – UK • Conduct comparative clinical studies vs. current practice, wherever feasible – UK, DE COST • Demonstrate any clear cost offsets and associated budget impact – IT, US, FR • Consider risk-sharing agreements – IT, AUS BURDEN OF DISEASE • Leverage advocacy group support – IT, FR, US • • • • Develop thorough definition of disease burden – FR Underscore the difficulty and rarity of the disease – AUS Include the patient perspective – IT Clearly define the patient population and provide robust evidence regarding patient numbers – UK RCT- Randomized Control Trial Post-Market Requirements United States EU / Australia Co-insurance/co-payment Risk-sharing • Study analyzed 9 drugs on exchange plans and found co-insurance between 10-50% & copayments between $20-$250 • Currently used in Italy and Spain • Expected future in Australia and US Prior authorization • Study found that as of 2012, 42 MEAs were required for 26 unique products • Used by all US payers interviewed Managed entry agreements Step-edits Re-assessment • • Drugs re-reviewed after 2-4 years on the market • Used in France Must fail another treatment before orphan drug is approved for use Split prescriptions Registry • • Study found that between 2007-2011 registries were required for 35% of orphans Dispense only half the prescription- used by US payer B Perceptions Future Landscape Cost cited as biggest future challenge- strategies varied Country Strategies to deal with future cost challenges AU Risk Sharing Agreements FR Defined thresholds DE Comparator requirement IT Risk sharing and monitoring ES Delay for the payment of medicines Central processing for payments of orphan drugs UK General population mobilized to address manufacturer profits US Closed formularies Risk Sharing Preferred Products Conclusions • Processes and requirements are currently fragmented and differ by payer which can lead to disparities in access • Payers are seeking more value based information as the cost and number of orphan drugs increase which could impact manufacturers strategies • Payer and manufacture roles are transitioning to include measurement of long-term outcomes, development of clinical guidelines, and patient drug management Recommendations • Future research needed to determine a cost-effectiveness threshold for orphan drugs • Develop a standard continued review process across Europe where data demonstrating clinical benefit was required longer into the product lifecycle Thank you Special thanks to: - Dr. John Paul- first reader - Dr. Susan Hogue- second reader - Faculty and staff at UNC-SPH - The RTI-HS staff - My fellow students - My Family 20 Appendices 21 Policy 1983 Promoting Rare Disease Drug Development 1991 US Orphan Drug Act • 7 years marketing exclusivity • Tax credits (≤ 50% clinical trial costs) • Waived user fees ($1.8 million)) 1993 1997 2000 Policy 1983 Promoting Rare Disease Drug Development 1991 Singapore • 10 years marketing exclusivity • Top registration priority on imports 1993 1997 2000 Policy 1983 Promoting Rare Disease Drug Development 1991 1993 Japan • 10 years marketing exclusivity • Tax credits and fee waivers • Priority review and fast track approval • Free protocol assistance 1997 2000 Policy 1983 Promoting Rare Disease Drug Development 1991 1993 1997 Australia • No market exclusivity • Fee reductions • Pre-licensing access, regulatory assistance 2000 Policy 1983 Promoting Rare Disease Drug Development 1991 1993 1997 2000 European Union • 10 years market exclusivity • No financial assistance • Free protocol and scientific advice Literature Review Search Criteria (“orphan drug” or “orphan drugs” or "orphan technology" or "orphan technologies") and (“payment” or "payer" or “insurance” or “access” or “reimbursement” or “Plan, Drug Benefit” or “Plans, Drug Benefit”) Questions: Orphan Drug Review Process 8. When are therapies for orphan / ultra-orphan indications typically reviewed? 9. How, if at all, does the review process for a therapy indicated for an orphan / ultra-orphan differ from the normal review process? 12. Is there a distinction between orphan status and ultra-orphan status when you are reviewing new therapies? 13. What happens when you receive the first claim for an orphan drug? Is it automatically denied and channeled through the appeals process? Questions: Factors that influence payer decisions 10. How should manufacturers persuade decision makers expecting to see a large randomized controlled trial that a small uncontrolled phase 2 study is an acceptable basis for judging the merits of the orphan/ultra-orphan therapy? 11. How should manufacturers persuade HTA committees/payer decision makers that they can bridge from the clinical evidence used for regulatory approval to clinical effectiveness and cost-effectiveness when there is added uncertainty? 16. What information will be necessary from the manufacturer for favorable formulary placement/ pricing and reimbursement or access at the time of launch? And in the longer term? 17. When the price of an orphan/ultra-orphan condition is almost always high, how can we mobilize other factors to enable an HTA committee/payer decision maker to say “yes”? Questions: Post Market Requirements 13. What happens when you receive the first claim for an orphan drug? Is it automatically denied and channeled through the appeals process? 14. Are there any orphan or ultra-orphan therapies or disease area that are highly restricted in terms of access? Questions: Payer Perceptions 7. What is your biggest challenge for the review of therapies for orphan/ultra-orphan indications? 15. How, if at all, do you think the pricing and reimbursement landscape / legislation in your country is likely to change for orphan / ultra-orphan drugs in the next 2-4 years? 18. With so many orphan / ultra-orphan drugs launching now, what challenges does this pose to you as a payer/HTA advisor?