a new era in hiv treatment: generics and quasi-generics
TRANSCRIPT
ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals
ANewErainHIVTreatment:GenericsandQuasi-Generics
TimHornDeputyExecutiveDirector– HIV&HCVPrograms,TreatmentActionGroup
Chair,FairPricingCoalition
ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals
LearningObjectivesUponcompletionofthispresentation,learnersshouldbebetterableto:
• DescribetheburdenofHIVprescriptiondrugpricingandthepotentialvalueofcostcontainment,includinglower-costbrand(“quasi-generic”)andgenericantiretroviralsinHIVtreatment
• Assesscomplexitiesofdrugpricingacrosspayor systemsandvariabilityofpotentialcostsavings
• DiscusscostasanincreasinglyimportantHIVtreatmentconsiderationandthepotentialforheightenedpayor regulation
ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals
FacultyandPlanningCommitteeDisclosuresPleaseconsultyourprogrambook.• TreatmentActionGroupreceivessupportfromViiV Healthcare,GileadSciences,Janssen
Pharmaceuticals,andMerck• TimHorndoesnotreceiveanydirectsupportorhonorariafromanypharma
Off-LabelDisclosureThefollowingoff-label/investigationaluseswillbediscussedinthispresentation:• Therewillbenooff-label/investigationalusesdiscussedinthispresentation
ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals
Organisation for Economic Cooperation and Development. https://data.oecd.org/healthres/pharmaceutical-spending.htm
PharmaSpending:%ofHealthSpending(2015)
OECDCountries
ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals
HealthSpending:US$Capita(2015)
OECDCountries
Organisation for Economic Cooperation and Development. https://data.oecd.org/healthres/pharmaceutical-spending.htm
ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals
PharmaSpending:US$Capita(2015)
OECDCountries
Organisation for Economic Cooperation and Development. https://data.oecd.org/healthres/pharmaceutical-spending.htm
Per-PersonSpending(2017)MedicaidACAMarketplacePlans
Express Scripts. 2017 drug trend report. http://lab.express-scripts.com/lab/drug-trend-report/~/media/2b56ec26c9a04ec2bcca0e9bf1ea8ff1.ashx
ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals
TheHIV(Treatment)Payor Patchwork
• Employer-basedplans• ACAMarketplacePlans• Medicaid/Medicare• VeteransAdministration• RyanWhite/ADAPs• Patientassistanceprograms&copay/coinsuranceassistance
WhyDrugPricingMatters
74.50% 57.00% 55.00%
90% 80%
DIAGNOSED L INKEDWITHIN1 MONTH
RETAINED IN CARE
VIRALLY SUPPRESSED
HIVCARECONTINUUM(2014)Achieved NationalGoals
• Needtodobetterwithfiniteresources• Evidenceofpayor resistance
– PreferenceforolderSTRs;MTRs• 20%ofplansonlycoveringEFV/TDF/FTC;15%ofplansnotcoveringanynew(>2013)ARVs2
– Highestcoveragetiers/coinsuranceamounts
• GrowingrecognitionofcostasstructuralbarriertoHIVpreventioncareandPrEP
1. CDC. Monitoring selected national HIV prevention and care objectives by using HIV surveillance data United States and 6 dependent areas, 2015. 22(2). 2. NASTAD. Discriminatory Design: HIV Treatment in the Marketplace. 2016 July. https://www.nastad.org/blog/discriminatory-design-hiv-treatment-marketplace
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ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals
ForecastingtheNeedforCostContainment
• OngoingeffortstorepealtheACA• NoMedicaidexpansionwhereitisneededmost• Medicaidblockgrants,workrequirements• IncreasingdependenceonADAPprescriptiondrugcoverage?• Politicalparadox
– bipartisanaversiontohighdrugpricesand doingsomethingboldaboutthem
ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals
ENTERGENERICS(ANDQUASI-GENERICS)
• Doravirine/TDF/3TC • EFV 400mg/TDF/3TC• EFV600mg/TDF/3TC• TDF/3TC
• Nevirapine (2012)• ABC/3TC (2016)• Atazanavir (2018)• Ritonavir (2018)• Darunavir (expected:2020?)• TDF/FTC (expected:2021?)
Single-SourceBrand(Innovator)Products
“Quasi-Generic”Brand(Innovator)Products
Multi-SourceGeneric(Non-Innovator)Products
• Cheapest• 6monthsexclusivitypossible• Competitionbasedondemand• Interchangeablewithbrand• Copayassist:Rarely
• Cheaperstill• Potentialcompetition• Notinterchangeablewithany
single-sourceproducts• Copayassist:yes(fornow)
• Cheaper(?)• Patent(20+years)and
exclusivity(5years)• Monopolyproducts• Copayassist:likely
Innovator:Newdrug(chemicalentitiesnotpreviouslyapprovedbyFDA)ornewformulationmanufacturerPatent:PTOdesignation;20-plusyearsofprotection,butfrequentlychallengedbygenericmanufacturersExclusivity:FDAdesignation,oftenconcurrentwithpatent;nogenericpatentchallengesduringthisperiod
ThreePathwaysforOff-PatentDrugs
RecommendedInitialRegimensforMostPeoplewithHIV
Recommendedregimensarethosewithdemonstrateddurablevirologicefficacy,favorabletolerabilityandtoxicityprofiles,andeaseofuse.
•INSTI+2NRTIs:DTG/ABC/3TCa (AI)—ifHLA-B*5701negative•DTG+tenofovirb/FTCa (AI forbothTAF/FTCandTDF/FTC)•EVG/c/tenofovirb/FTC(AI forbothTAF/FTCandTDF/FTC)•RALc +tenofovirb/FTCa (AIforTDF/FTC,AII forTAF/FTC)
RecommendedInitialRegimensinCertainClinicalSituations
Theseregimensareeffectiveandtolerable,buthavesomedisadvantageswhencomparedwiththeregimenslistedabove,orhave lesssupportingdatafromrandomizedclinicaltrials.However,incertainclinicalsituations,oneoftheseregimensmaybepreferred.
•BoostedPI+2NRTIs:(Ingeneral,boostedDRVispreferredoverboostedATV)(DRV/corDRV/r)+tenofovirb/FTCa (AI forDRV/randAII forDRV/c)•(ATV/corATV/r)+tenofovirb/FTCa (BI)•(DRV/corDRV/r)+ABC/3TCa —ifHLA-B*5701–negative (BII)•(ATV/corATV/r)+ABC/3TCa —ifHLA-B*5701–negativeandHIVRNA<100,000copies/mL (CI forATV/randCIII forATV/c)
NNRTI+2NRTIs:EFV + tenofovirb/FTCa (BI forEFV/TDF/FTC andBIIforEFV +TAF/FTC)•RPV/tenofovirb/FTCa (BI)—ifHIVRNA<100,000copies/mLandCD4>200cells/mm3
INSTI+2NRTIs:RALc +ABC/3TCa (CII)—ifHLA-B*5701–negativeandHIVRNA<100,000copies/mL
RegimenstoConsiderwhenABC,TAF,andTDFCannotbeUsed:d DRV/r+RAL(BID)(CI)—ifHIVRNA<100,000copies/mLandCD4>200cells/mm3
•LPV/r+3TCa (BID)e (CI)
WhereasTDFandTAFarecomparableand3TCandFTCareinterchangeable
HHS. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. 2017 October 17. https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/0
ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals
HHS-RecommendedCoformulated NRTIs
• TDF/3TC(2018)• Quasi-generic/branded• Nodirectcompetition(yet)• Bioequivalenttostand-aloneTDFand
stand-alone3TC• Comparators:TDF/FTC,TAF/FTC(?)
– ~$1,000vs.$1,650/month
• Copayassistanceexpected• NOTAPPROVEDFORPrEP!!!
• ABC/3TC (2016)• Generic/unbranded• Severalcompetitors• Bioequivalenttobrand-name
coformulated ABC/3TC• Comparator:brandedABC/3TC
– ~$115vs.$1,250/month
• Nocopayassistance
Low(er)-doseEFV,TDF,and3TC
• Contains400mgEFVand3TC(vs.600mgEFVandFTCinstandardSTR)
• Int’lENCORE1trial(n=630)– Non-inferiortostandardSTR– NodifferenceinfrequencyofA/Es,d/crates,QoL,etc.
– A/Es relatedtostudydrugmorefrequentinstand.arm(p=0.008)
• U.S.WAC40%<EFV/TDF/FTC– ~$19,000vs.~$32,000;copayassist.
ENCORE1 Study Group. Efficacy of 400 mg efavirenz versus standard 600 mg dose in HIV-infected, antiretroviral-naive adults (ENCORE1): a randomised, double-blind, placebo-controlled, non-inferiority trial. Lancet. 2014 Apr 26;383(9927):1474-1482.
ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals
Approval≠Availability
• Genericapprovaloftenprecedescommercialavailability– ritonavir(2015)lopinavir/r(2017),darunavir(2017),TDF/FTC(2017)
• Availabilitylargelydeterminedbypatentchallengerulingsandconfidentialagreements
• BestguessforlaunchofgenericTDF/FTC:2021
ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals
YES,BUTWILLTHEYREDUCECOSTS?
SavingsfromGenerics:$253Billionin2016
Association for Accessible Medicines. 2017 Generic Drug Access and Savings in the U.S. Report. https://accessiblemeds.org/resources/blog/2017-generic-drug-access-and-savings-us-report
GenericsCostSavings:HIV
Walensky RP, et al. Economic savings versus health losses: the cost-effectiveness of generic antiretroviral therapy in the United States. Ann Intern Med. 2013 Jan 15;158(2):84-92. Martin EG, Schackman BR. Treating and Preventing HIV with Generic Drugs - Barriers in the United States. N Engl J Med. 2018 Jan 25;378(4):316-319.
ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals
Generics
AverageWholesalePrice(AWP)
WholesaleAcquisitionCost(WAC)
AverageManufacturerPrice(AMP) NonfederalAverageManufacturerPrice(Non-FAMP)
FederalSupplySchedule(FSS)Price
FederalCeilingPrice
FederalCeiling;“Big4”Price
BestPrice
MedicaidPrice340BPrice
Privatesectorprices
RebatestoPBMsCopayassistance
Otherpriceconcessions
Unitrebate:23.1%/13%ofAMPorAMP– BestPriceplus
CPIpenalties
76%ofnon-FAMPminusadditionaldiscounts
Supplementalrebatesanddiscountsnegotiated(includingADAPs)
Supplementaldiscountsnegotiated(VAandDoD)
Negotiationonmost-favoredcommercialcustomerprice
DrugPricing:TheSimpleVersion
FederalUpperLimit
StateMaximumAllowableCost
ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals
Generics
AverageWholesalePrice(AWP)
WholesaleAcquisitionCost(WAC)
AverageManufacturerPrice(AMP) NonfederalAverageManufacturerPrice(Non-FAMP)
FederalSupplySchedule(FSS)Price
FederalCeilingPrice
FederalCeiling;“Big4”Price
BestPrice
MedicaidPrice340BPrice
Privatesectorprices
RebatestoPBMsCopayassistance
Otherpriceconcessions
Unitrebate:23.1%/13%ofAMPorAMP– BestPriceplus
CPIpenalties
76%ofnon-FAMPminusadditionaldiscounts
Supplementalrebatesanddiscountsnegotiated(includingADAPs)
Supplementaldiscountsnegotiated(VAandDoD)
Negotiationonmost-favoredcommercialcustomerprice
¯\_(ツ)_/¯
FederalUpperLimit
StateMaximumAllowableCost
ARVRegimen RetailPharmacy AcquisitionCost
BrandName
DTG +TDF/FTCorTAF/FTC $3,226/month
ELV/CABO/TAF/FTC $2,944/month
DTG/ABC/3TC $2,718/month
Mixed (BrandandQuasi-genericorGeneric)
DTG +TDF/3TC $2,603/month*
DTG+ABC/3TC $1,730/month
AllGeneric
NVP+ ABC/3TC $131– $388/month
National Average Drug Acquisition Cost (NADAC) database. https://data.medicaid.gov/Drug-Pricing-and-Payment/NADAC-National-Average-Drug-Acquisition-Cost-/a4y5-998d
*NADAC data for TDF/3TC not available; based on WAC price.
ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals
MarketForcesRule
• UniquetoHIVcare:limiteddemandamongpatientsandproviders• Payors andthepowerof“NO”• Utilizationmanagement:steptherapy
– Example:DTGplusTDF/3TCorABC/3TC,switchtoBIC/TAF/FTCorDTG/ABC/3TCwithrenal/bone/adherenceneeds
– Difficultyofimplementingpopulation-levelcost-containmentmeasuresinthefaceofindividualizedtreatmentneeds
– Thebigrisk:poorvirologicsuppression,resistance,riskoftransmissionshouldMTRfactorintoadherencechallenges
ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals
WhoBenefitsfromCostSavings?
• NoclearpathwayforreinvestingcostsavingsinHIVpreventionandcare• Recognizeindirectsavingstopurchasesandpayors,alongwithsocietalbenefits
• DoPLWHIVbenefit?– Lowcopaysongenericsvs.copayassistanceformonopolyproducts?– Mightsafetyandadherencerisksoutweighcostsavingspotential?
ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals
PATIENTANDPROVIDERPREFERENCE
ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals
Patient&ProviderChoice:TheBigQuestions
• IsTAFpreferabletoTDFforall PLWHIV?– TAFmorefavorableeffectsonrenalmarkersandBMD,butTDFstillaGuidelines-recommendedcomponentofinitialregimensformostpeoplewithHIVbasedonwell-establishedsafetyandefficacy
• AreQDSTRspreferabletoQDMTRsforall PLWHIV?– STRsareeasiertousewithfewermonthlycopays,butdatasupportingorrefutingsuperiorityarelimited;STRsandMTRsamongGuidelines-recommendedinitialregimensformostpeoplewithHIV
STRtoMTRSwitches:Patient&ProviderAttitudes
• SouthernAlberta,Canada• 13providers,607DTG/ABC/3TCSTRusers
• Survey:SwitchfromSTRtoDTGplusgenericABC/3TC?
• Allproviders:de-simplifyingcouldbedonesafely
• Patients:Mixedagreeability
Yes,foraltruisticreasons48%
Maybe25%
No
27%
SURVEYRESPONSES
Krentz HB, et al. Patient perspectives on de-simplifying their single-tablet co-formulated antiretroviral therapy for societal cost savings. HIV Med. 2018 Apr;19(4):290-298.
ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals
CaseQuestion
• A26-year-oldmalewhorecentlytestedpositiveforHIVpresentsforcare.HiseGFR is120mL/min/1.73andheisHLA-B*5701negative.YouprescribeBIC/TAF/FTCbuthisinsurancerejectstheclaimonthegroundsofaformularypreferencefor:– EFV/TDF/FTCorEFV/TDF/3TC,or– DTGplusquasi-genericTDF/3TC(coformulated),or– DTGplusgenericABC/3TC(coformulated)
ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals
Yournextstepisto:
1. CounselpatientandresubmitprescriptionforDTGplusTDF/3TC2. CounselpatientandresubmitprescriptionforDTGplusABC/3TC3. CounselpatientandresubmitprescriptionforEFV-basedSTR4. Appealimmediately,atriskofdelayingtherapystart
ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals
ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals
Conclusion• It’shere:eraofARVdrugcostconsiderations• Genericsandquasi-genericscanpotentiallyincreasecompetitionandleadtolowerpricesforpurchasersandpayors– Somepayors willlikelybenefitmorethanothers
• Providersandpatientsshoulddiscusspricingandaccess,alongwithefficacy,safety,andeaseofadministration
• Increasedpayor regulationofformulariespossible– Needstrongguidelinesaddressingwhenthisisacceptableorunacceptable– Reportoverlyrestrictive/dangerousmeasures:speakup.hiv