Creating collaborative systems to address orphan drugs in a sustainable way – update from Europe
Creating collaborative systems to address orphandrugs in a sustainable way – update from EuropeWills Hughes-Wilson, VP Global Public Policy & Government Relations, SobiMember of the EU Committee of Experts on Rare Diseases (EUCERD)Chair, Joint European Industry Task Force on Orphan Drugs (EuropaBIO + EBE)Orphan Café, Leiden, 30 May 2012
Orphan Medicinal Products – “a balancing act”2• Sense of urgency• High, unmet medical need• Serious, life-threatening conditions• But few patients, few data• Risk:benefit = positive• Acceptance that it is ethical to move forward• (Regulatory) acceptance, despite overall weight ofevidence not so available• Compared with more common conditions
Results of the approach =drugs are being developed & approved30102030405060708090ODs with EU Positive Opinion ODs removed from EU Community Register* 3rd Quarter 2011
“Balancing act” creates uncertainty –and has an impact on all stakeholders4• Victims of success of the Regulation?• ~55 therapeutic areas = “4,945 to 6,945 still to go?!”• Governments seeking to understand the value ofwhat they are being offered• How can we tell?• Small datasets, surrogate endpoints, non-routine clinicaltrial design, early approval…• Some of the systems tried to date – NL – havereportedly not been so successful for governments?• “IS IT SUSTAINABLE?” Financially? Socially?
Creates a gap between Marketing Authorisation(EU) & Access to Patients (Country / EU Member State)5Timeline graphic courtesy of Ernst & Young, CAVOD study, December 2011Data Assessment Appraisal
This is important because…6• Customers – those who pay* – are thinking aboutvalue• What is it?• How do they measure it?• What is it worth?* Gatekeepers to patient access…
Situating the approach toorphan drugs in the wider external context71. Evolving cooperative environment between HTAbodies – cross-border cooperation2. Legislation to address uncertainty – newPharmacovigilance legislation
“Orphan” & “non-orphan”tools exist to make it possible• “Cross-Border HealthcareDirective” creates legalframework for furthercooperation• Rare Diseases as a focusHealthcare provisionremains a Member State responsibility…but no longer in isolation
1. “Cross-Border Healthcare Directive” – 9 March 20119• European reference networks (Article 12)• Explicit focus in regular reporting (Article 20)• Permanent Network of HTA bodies (Article 15)• Rare Diseases as a particular focus (Article 13)
2. New Pharmacovigilance Legislation10• …“post-authorisation efficacy studies whereconcerns relating to some aspects of the efficacy ofthe medicinal product are identified and can beresolved only after the medicinal product has beenmarketed”• PRAC requirements captured in CHMP Opinion• Post-Marketing-Authorisation data-gathering• Coordination vital – building on early dialogue
What is true for drugs generallyis PARTICULARLY true for orphan drugs11October 2008: Grouping of 27 Member States agreeprinciples on orphan drugs as area of focus because“these [orphan] medicines amplify strongly thecommon tensions we have found in the field ofpricing and reimbursement: assessing andrewarding innovation is difficult, budgetoptimisation is challenged and access for patients islimited in several countries”.
Countries facing the same questions –Collaboration & cooperation as a way forward12• Particular need in the case of orphan drugs: rarity –data & expertise• Assessments need Methodologies & Agencies• Takes time & resources• Sharing / building something together rather thancreating de novo 27 times• Best practice, experience• Particular political focus on rare diseases & OrphanDrugs with actions
European initiatives will interact to createthe framework for understanding orphan drugs131. CAVOD – Clinical Added Value of Orphan Drugs2. MOCA – Mechanism of Coordinated Access toOrphan Drugs3. EUCERD Work Programme4. National Plans for Rare Diseases5. …the future?
Gap between Marketing Authorisation (EU)& Access to Patients (Country / EU Member State)15Timeline graphic courtesy of Ernst & Young, CAVOD study, December 2011Data Assessment Appraisal
Four key time-points in the processof an orphan drug where collaboration could help161. Early dialogue2. Compilation report & evidence-definition /Evidence-Generation plan3. Follow up of the Evidence Generation Plan4. Assessment of Relative EffectivenessRespecting the roles and responsibilities within theexisting systemBreaking down “silos” – bridging the gap
TimeOrphanDesignationSignificantBenefit COMPProtocolAssistanceCHMP OpinionT0EC MarketingAuthorisationT0 + 90 daysT0+∆T(after 3-5 years, flexible,depending on the diseasePeriod 1:For EMA / EUnetHTAcoordinationPeriod 2:For simpleCompilation report &evidence generation planPeriod 3:For follow-up of theevidence generation planPeriod 4:Relative effectivenessassessmentEarly DialogueCompilation Report& Evidence Needs Identification• EMA• EUnetHTA• Sponsor1st assessmentof SignificantBenefitConfirmation ofSignificantBenefit• EMA (Report)• EUnetHTA• EMA• EUnetHTA• MAHEvidence generation Assessment• EUnetHTA• EMA• Could beimplementedalready• Actions required?• Report could be implementedimmediately• Involvement with PRACrequirements needs more work• Evidence generation plans& follow-up would need tobe defined• Other?• Appropriatemethodologies / toolsfor OMPs to bedeveloped
Characteristics to aid success18• Case-by-case• Heterogenous conditions, therapies, situations• Voluntary• Respecting the systems, roles & responsibilities• Multi-stakeholder involvement• Developing the right tools for the job• Measured• Does it work? Periodic reporting
Formulating Policy into Reality:where in the process & what next?19• 26-27 January 2012 – EUCERD endorses direction• 9 May 2012 – updated by EUCERD drafting group• 19 June 2012 – enlarged drafting group• 20-21 June 2012 – EUCERD Plenary (adoption?)[or November 2012 EUCERD meeting]• Next steps from relevant authorities to implement• Start with what we can: pilots by year-end?“Oil in the machine”, not a new machine
Gap between Marketing Authorisation (EU)& Access to Patients (Country / EU Member State)21Timeline graphic courtesy of Ernst & Young, CAVOD study, December 2011Data Assessment Appraisal
Mechanism of CoordinatedAccess to Orphan Drugs (MOCA)22• Create a tool for governments at time of pricing &reimbursement• Create (more uniform) access• Control costs?• “Whoever wants to give access” – have a “tool athand that he/she could follow”:• From identification of potential solution (orphan drug)• Through identifying what it’s worth• To delivering to actual treatment of patient• 15 countries – to create shared mechanism
23Mechanism of Coordinated Accessto OrphansFRUKESPTITDECZBENL PLROBGELIEHUSEFIATCYLTLVEEDKSKLUSLHRSRMKBHALCHNOUKRUKRUSSIATRBYISWill joinBut it is not a closed club!Member States can signup at any time to participatein developing the mechanismShared mechanism betweenthe 15 countries involved
24Identifying and assessingRelevant OMPs – procedural steps flowchartStart: Rare DiseaseClassificationOrphan DrugDesignation by COMPCoordinated HorizonScanningEarly DialogueAdvice Incorporatedinto ClinicalDevelopment PlansMarketingAuthorisationApplicationMarketingAuthorisation Processat EMACHMP Positive OpinionTherapeutic / ScientificCompilation Reports**End: EuropeanCommission MarketingAuthorisationEarly AccessProgrammes(regulatory or countrylevel driven)Discussion with MemberStates***/***Potential links with other Work Packages** Potential link with other initiatives in development, e.g. the different stages in the proposed CAVODprocess
OperationalstepImplementingactivityOutputEU level:EURORDISPatientsassociations atnational levelORPHANETEPIRARENumber of patients ineach country affectedby the (rare) diseaseand elegible fortreatment withorphanPatient numberidentification(PNI)(Selection of the targetpopulation)PNI as orphanmedicinalproductdesignationPNI asPatients`AssociationsPNI as Platformsad hoc andEuropean/national RegistriesValuableorphanmedicine(WP1)IRDIRCNationalcentres ofreferenceAnalysis of pricingsystems for orphans inMSActual costs of medicine/s(transparentmechamism ofcalculation)(TransparentPricing Matrix)Rule-basedCeillingprice/thresholdperdrug/diseaseExpenditure forecast(affordability)FrameworkAgreement with anaward decision/statement of ceilingprice and/or MEA)Nationalprocedures forP&R (local MSprice)Nationalreimbursementand price decisionJointProcurementPricing/Procurement(Funding mechanism)Outcomes onaffordability,costs andprofitabilityNegotiationsbased on healthimpact*Joint Reimbursement byHealth Impact Fund (forinnovation) and by memberstates (for production costs)Alternativemechanism*The Health Impact Fund is a proposed new way of paying for pharmaceutical innovation. a firm agrees to provide its drug at cost where it is needed, and in exchange for foregoing the normal profits fromdrug sales, the firm is rewarded based on the HIF’s assessment of the actual health impact of the drug. Payors would finance the HIF. See http://www.yale.edu/macmillan/igh/.This scheme was developed for financing drugs in developing countries. However, it may be adapted for financing orphan drugs.
Parameter Lower Degree Medium Degree High Degree1:2 000-1 to 1:20 000 1:20 000 to 1:200 000 less than 1:200 000Number of Patients in EU (Pop. 500000 000)25 000 to 250 000 2 500 to 25 000 less than 2 500Available Alternatives/Unmet Need(Innovation)yes, new drug does not address unmetneedyes, but major unmet need stillremainsno alternatives except best supportivecare - new drug addresses majorunmet needRelative Effectiveness, Degree of NetBenefit (Clinical Improvement,QoL, etc. vs. side effects) relativeto alternativesincremental major curativeResponse Rate (based on best avialableselection criteria)<30% 30-60% >60%Degree of Certainty (Documentation) promising but not well-documented plausible unequivocalReplaced by a proposedmulti-criteria approach to understand value?…under discussion
Timelines & next steps27• 27 April 2012 – MOCA Topic Leaders finalise draft• 11 May 2012 – workshop 15 countries +stakeholders• Summer 2012 – write-up of project proposals• November 2012 – presentation of final report• END-2012 – delivery of final product• Final report• TOOL• Manual of definitions, objectives & instructions
3. Specific approaches & programmes to buildsystems for orphan drugs28
Elements from Commission Communication willcombine to build true “Eco-System” for Orphan Drugs29CHAPTER 5 includes actions on:• Centres of Expertise & EU Reference Networks• Access to Orphan Drugs• Compassionate Use programmes• Incentives for Orphan Drug development• Screening practices• Diagnostic laboratories• Research & development• Registries & databases
Individual “how to” elementsbeing developed by the EUCERD30
EUCERD: EU Committee of Experts on Rare Diseases31• 27 EU Member States (1 + 1 alternate)• Patients• Industry• Academia / representatives of European-funded projects• European Commission, ECDC• EMA, COMP – request to be present• 3rd Countries [non-EU]The EUCERD’s role is to aid the European Commissionwith the preparation and implementation ofCommunity activities in the field of rare diseases.
Individual “how to” elementsbeing developed by the EUCERD32• Quality Criteria on Centres of Expertise: Oct 2011• Recommendations on CAVOD (under consideration)• Draft Recommendations for European ReferenceNetworks (in process)• New-Born Screening in Europe – proposals for nextsteps (under discussion)• …
Political commitment by 27 EU governments forNational Plan for RD in each EU Member State by 201334If plans are similar,they can linktogether to createa European areafor rare diseasediagnosis,treatment,research…
Collaborative work to build National Plans continues35• EUROPLAN recommendations adopted• New EUCERD Joint Action (funding) includes furtherwork with countries• 20 new conferences 2012-2013• Indicators, measurables and success criteria• EUCERD will report formally• Potential benchmarking report by EuropeanParliament
The proposed Rare Disease treatment paradigm – themodel for the future of sustainable healthcare systems?37CommissionCommunicationCouncilRecommendationTreatmentc- Effective- Cost-effective- Sustainable- Meeting payers’ needsCentresofExpertiseRegistriescCould this be the way forward for all innovative drugs?ConfirmedDiagnosisDoseadjustmentOutcomesCAVODHTA(Rel. effectiveness)Reimbursement/ Reimb. revisionCUP / Reimb. (in dev.)