Download - A New Era in HIV Treatment: Generics and Quasi-Generics

ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals

ANewErainHIVTreatment:GenericsandQuasi-Generics

TimHornDeputyExecutiveDirector– HIV&HCVPrograms,TreatmentActionGroup

Chair,FairPricingCoalition


LearningObjectivesUponcompletionofthispresentation,learnersshouldbebetterableto:

• DescribetheburdenofHIVprescriptiondrugpricingandthepotentialvalueofcostcontainment,includinglower-costbrand(“quasi-generic”)andgenericantiretroviralsinHIVtreatment

• Assesscomplexitiesofdrugpricingacrosspayor systemsandvariabilityofpotentialcostsavings

• DiscusscostasanincreasinglyimportantHIVtreatmentconsiderationandthepotentialforheightenedpayor regulation


FacultyandPlanningCommitteeDisclosuresPleaseconsultyourprogrambook.• TreatmentActionGroupreceivessupportfromViiV Healthcare,GileadSciences,Janssen

Pharmaceuticals,andMerck• TimHorndoesnotreceiveanydirectsupportorhonorariafromanypharma

Off-LabelDisclosureThefollowingoff-label/investigationaluseswillbediscussedinthispresentation:• Therewillbenooff-label/investigationalusesdiscussedinthispresentation


Organisation for Economic Cooperation and Development. https://data.oecd.org/healthres/pharmaceutical-spending.htm

PharmaSpending:%ofHealthSpending(2015)

OECDCountries


HealthSpending:US$Capita(2015)

OECDCountries



PharmaSpending:US$Capita(2015)

OECDCountries


Per-PersonSpending(2017)MedicaidACAMarketplacePlans

Express Scripts. 2017 drug trend report. http://lab.express-scripts.com/lab/drug-trend-report/~/media/2b56ec26c9a04ec2bcca0e9bf1ea8ff1.ashx


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

1


ForecastingtheNeedforCostContainment

• OngoingeffortstorepealtheACA• NoMedicaidexpansionwhereitisneededmost• Medicaidblockgrants,workrequirements• IncreasingdependenceonADAPprescriptiondrugcoverage?• Politicalparadox

– bipartisanaversiontohighdrugpricesand doingsomethingboldaboutthem


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


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.


Approval≠Availability

• Genericapprovaloftenprecedescommercialavailability– ritonavir(2015)lopinavir/r(2017),darunavir(2017),TDF/FTC(2017)

• Availabilitylargelydeterminedbypatentchallengerulingsandconfidentialagreements

• BestguessforlaunchofgenericTDF/FTC:2021


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.


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


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.


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


WhoBenefitsfromCostSavings?

• NoclearpathwayforreinvestingcostsavingsinHIVpreventionandcare• Recognizeindirectsavingstopurchasesandpayors,alongwithsocietalbenefits

• DoPLWHIVbenefit?– Lowcopaysongenericsvs.copayassistanceformonopolyproducts?– Mightsafetyandadherencerisksoutweighcostsavingspotential?


PATIENTANDPROVIDERPREFERENCE


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.


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)


Yournextstepisto:

1. CounselpatientandresubmitprescriptionforDTGplusTDF/3TC2. CounselpatientandresubmitprescriptionforDTGplusABC/3TC3. CounselpatientandresubmitprescriptionforEFV-basedSTR4. Appealimmediately,atriskofdelayingtherapystart


Conclusion• It’shere:eraofARVdrugcostconsiderations• Genericsandquasi-genericscanpotentiallyincreasecompetitionandleadtolowerpricesforpurchasersandpayors– Somepayors willlikelybenefitmorethanothers

• Providersandpatientsshoulddiscusspricingandaccess,alongwithefficacy,safety,andeaseofadministration

• Increasedpayor regulationofformulariespossible– Needstrongguidelinesaddressingwhenthisisacceptableorunacceptable– Reportoverlyrestrictive/dangerousmeasures:speakup.hiv

Download - A New Era in HIV Treatment: Generics and Quasi-Generics

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