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1、Follow-On Biologics:Economic,Innovation and Policy Reflections The Fuqua School of BusinessDuke University,November 6-7,2008,Charles DiLiberti,V.P.Global Pharmacokinetics and Bioequivalence,Barr Laboratories,Inc.,“Commercial Opportunities and Challenges for Follow-on Biologics”,Presentation Overview
2、,Generic BiologicsCommercial Opportunities&SavingsScience&Technology ChallengesRegulatory&Intellectual Property IssuesSummary,Commercial Opportunities&Savings,Benefits of Generic Competition,Significant Cost Saving OpportunitiesSavings for consumers and taxpayersGeneric Competition Will Fuel Innovat
3、ionBrand companies will have the incentive needed to vigorously pursue new biologics,Increasing Significance of Biologic Products,US Biologic Revenues1997:$17.4 Billion2007:$65.2 Billion*400 Biologics&Vaccines Currently in Clinical Trials Targeting 200 Diseases*Between 2003 and 2006,biologics repres
4、ented 24%of all new chemical entities approved by the US*Sales of biotech products in the US showed an annual growth rate of 20%between 2001 and 2006 compared with 6%to 8%in the pharmaceutical market*,*Ernst&Young*Biotechnology Industry Organization*Journal of American Medical Association,October 22
5、,2008,High Cost of Brand Biologics,Annual Cost per Patient Enbrel(Arthritis)$20,000*Cerezyme(Gaucher Disease)$200,000*Remicade(Arthritis)$35,000-$66,000*Generic Competition Will Reduce These Costs,*Baltimore Sun January 28,2007*Bloomberg January 11,2007*Philadelphia Inquirer September 19,2006,Signif
6、icant Cost Savings Opportunity,Generic Biologics Represent Significant Cost Savings Opportunities and Stimulate Innovation,EpogenMarket Before Generic Launch:$2.5 Billion*Brand/Year Today:$9,000*Generic Savings/Year assuming 50%savings:$4,500,EnbrelMarket Before Generic Launch:$2.7 Billion*Brand/Yea
7、r Today:$20,000*Generic Savings/Year assuming 50%savings:$10,000,*ABN AMRO February 2008*National Journal February 10,2007*Baltimore Sun January 28,2007,Generic Competition,Price Drops as Number of Manufacturers Increases,Market Size for Select Biologic Products,Source:ABN AMRO February 2008,Market
8、Size for Select Biologic Products,Source:ABN AMRO February 2008,Perspective:Historical Growth in Substitution,Source:IMS Health,Banc of America Securities LLC estimates,Generic BiologicsOpportunity,Generic Pharmaceuticals-A Vital Part in Health Care SystemApproximately 67%of the Prescriptions Dispen
9、sed in the US Are Generics*BiologicsWorldwide Market Estimated around$75 Billion*Per Patient Cost for Biologic Products Can Exceed$100,000 Per Year Generic BiologicsUS Consumers Could Save$43 Billion Between 2011 and 2020*Estimated Value of Biologics that have already lost Patent Protection:$10 Bill
10、ion*Estimated Value of Biologics to lose Patent Protection in the Next Ten Years:$20 Billion*,*IMS Health*Citizens Against Government Waste(CAGW)Release,May 2,2007*ABN AMRO February 2008,Science&Technology Challenges,Scientific Challenges for Generic Biologics,CharacterizationSafety AssessmentTherap
11、eutic EquivalenceManufacturing Controls,Generic Biologics,Generic biologics,sometimes called follow-on biologics(FOBs),are protein products that are pharmaceutically and therapeutically equivalentGeneric biologics do not utilize the reference products proprietary process,specifications or clinical d
12、ata For established products,therapeutic equivalence can be demonstrated usingIn vitro studies and/orPharmacokinetics and/orSurrogate markers and/orClinical outcomesdepending on the characteristics of the protein,Biologics Size Does Matter.,Misinformation Campaign About Generic Biologics,Myth:Raw ma
13、terials of biologic origin are hard to source and only brand biotechs know where to find them.Reality:Raw materials are available today for many generic biologics including insulin,G-CSF,erythropoietin,interferons,etc.,Misinformation Campaign About Generic Biologics,Myth:Biologics are too complicate
14、d to be characterized.Reality:Numerous highly sophisticated analytical methods have been developed,permitting complete characterization.More advances will be achieved each year.,Misinformation Campaign About Generic Biologics,Myth:Generic companies lack the medical,scientific,and technical ability t
15、o produce safe and effective biotech products.Reality:Generic companies can and do make safe and effective biologics.Many safe and effective biologics currently are made in controlled environments and marketed by generic companies outside the U.S.,Generic Biologics(Biosimilars)in the EU,The ability
16、to make generic biologics is far from a theoretical possibility.In 2004 EU issued EMEA Draft Guidelines for four classes of generic biologics,referred to as biosimiliars in the EU.Since 2004,the EU has approved several biosimilar products.,EU Biosimilar Approvals,DRUG EU MARKET AUTHORIZATION DATESan
17、dozs Omnitrope(somatropin)April 12,2006BioPartners Valtropin(somatropin)April 24,2006Sandozs BinocritMedices AbseamedHexal Biotechs Epoetin alfa Hexal(recombinant human erythropoietin alfa)August 28,2007Stada Arzneimittels Silapo Hospiras Retacrit(epoetin zeta)December 18,2007Tevas TevagrastimRatiop
18、harms RatiograstimRatiopharms Filgrastim ratiopharmCT Arzneimittels Biograstim(human G-CSF)September 15,2008 current through September 25,2008,FDA Approves Sandozs Omnitrope,There has been some movement in the US to approve generic biologics.FDA approved Omnitrope in May 2006.FDA stated,however,that
19、 this approval does not create a pathway for all generic biologics.Omnitrope referenced a brand product(Genotropin)approved under the FDCA.,Misinformation Campaign About Generic Biologics,Myth:“The Product is the Process.”Reality:“Old models and mantras are inhibiting progress the product is no long
20、er the process.”(Statement of Mathias Hukkelhoven,Ph.D.,Senior V.P.,Global Head,Drug Regulatory Affairs,Novartis,Sept.14-15,2004).,Misinformation Campaign About Generic Biologics,Reality(continued):Biotech products can be fully characterized and compared analytically.Biotech Firms routinely justify
21、their own process changes via FDA approved comparability protocols.,Development of Generic Biologics,Strictly Controlled Process(Validated)Extensive Analytical Comparability(Characterization)Comparable Biological Activity(In Vitro/In Vivo)Non-Clinical Comparability(Safety,Immunogenicity.)Comparable
22、pharmacokinetics(blood concentration profile)Comparable Clinical Efficacy and Safety,Development Considerations,Product ComplexityFrom Development To ClinicalCharacterizationBiosynthesis,In-Process and Finished ProductNomenclatureLack of Strict Definition,INN IssueHigh Cost of Development Marketing
23、Requirements and CostPost-Marketing Safety SurveillanceIP Strength,Regulatory&Intellectual Property Issues,Challenges for Generic Biologics,RegulatoryCongress needs to create an abbreviated approval pathwayIntellectual PropertyBrand exclusivityGeneric exclusivityResolution of patent litigation prior
24、 to generic launch,Regulatory Issues,Regulatory Framework Complicated By Existence of Two Laws For BiologicsFDCA for NDA ProductsPHSA for BLA Products NDA Products Generic Pathway Exits,But FDA Implementation Is UnclearBLA ProductsThree Issues Need To Be ResolvedMechanics of Approval Pathway Need To
25、 Be DefinedBrand/Generic ExclusivityAn Efficient Patent Dispute Resolution Mechanism,Abbreviated Generic Pathway Under PHSA,A Generic Pathway Should:Give FDA Authority To Decide Approval Requirements For Generic ProductsAdopt Exclusivity Provisions No Greater Than Those Found In Hatch-WaxmanPermit P
26、re-Launch Adjudication of Certain Patent Disputes,Abbreviated Generic Pathway Under PHSA,FDA should be permitted to decide what tests/data are necessary for approval as a comparable or interchangeable generic.Congress should not impose unnecessary barriers to generic approvals,e.g.,mandatory guidanc
27、e or rule-making requirements;mandatory clinical trials;requirement that generics seek approval for all approved brand uses.,Abbreviated Generic Pathway Under PHSA,Congress should carefully consider any new,additional exclusivities awarded to brand biologics.Considerable incentives already exist for
28、 brand biotech companies.,Existing Incentives for Brand Biotech Companies,Abbreviated Generic Pathway Under PHSA,If Congress decides to give additional exclusivities to brand companies,Hatch-Waxman establishes the maximum length and number of exclusivities that can be justified:-5 years for truly ne
29、w,innovative products-3 years for certain improvements to already-approved brand products,Abbreviated Generic Pathway Under PHSA,Unlike the incentives that already exist to develop new brand biologics,no incentives exist to develop generic biologics.Generic biologics legislation should include an in
30、centive,just as Hatch-Waxman does for small molecule drugs,for the development of generic biologics.,Abbreviated Generic Pathway Under PHSA,Effective generic biologics legislation will include a mechanism for expeditious resolution of patent disputes.Hatch-Waxman has shown that patent mechanisms can
31、 be abused to delay generic market entry.,Abbreviated Generic Pathway Under PHSA,Only those patent disputes that would cause the generic company to delay launch should be litigated simultaneously with the FDA approval process.Disputes over any other patent that the brand owns should wait until the g
32、eneric company actually launches.,Abbreviated Generic Pathway Under PHSA,Such a process ensures that brand companies cannot use weak or suspect patents to delay generic market entry.At the same time,the process protects all legitimate patent rights it allows litigation over all patents,but controls
33、when that litigation can start so that generic marketing isnt unduly delayed.,Negotiations Are OngoingMuch Momentum Gained in DebateOptimistic for Ultimate Resolution,Regulatory IssuesU.S.Proposed Legislation,Summary,Generic Biologics in US,Significant Momentum in US CongressFailed to Pass in 2007-08 Session;Likely to Be On Legislative Agenda in 2009Strong Consensus for Generic Biologics Among Payers,Consumer GroupsDebate Centers On Three IssuesMechanics of PathwayHow to Resolve IP IssuesExclusivity Issue,State Governors,Broad,Bipartisan Support for a Workable Pathway for Generic Biologics,
