COLLEGIUMPRESENTATIONTODFC

StevePassik,PhD

VPScientificAffairs,Education,andPolicyMay17th,2018

CollegiumPharmaceuticalMission

•Collegium’smissionistobetheleaderinresponsiblepainmanagementbydevelopingandcommercializinginnovative,differentiatedproductsforpeoplesufferingfrompainandthecommunitiesweserve

TheOpioidPendulum:WhereAreWeNow?

1Gourlay,D.L.etal. Universalprecautionsinpainmedicine: A rationalapproachto thetreatment ofchronicpain.PainMedicine.2005;6(2):107-112.

OpioidPrescribingandtheHealthcareSystem

•Whathasincreasedopioidprescribingexposedinourhealthcaresystem?

•Wheredoesourhealthcaresystemfail?

•Chronicity

•Conditionswith major motivational/psychiatriccomponent

•CARECOORDINATION:Communicationamongprofessionals

•Ongoingriskassessment

•Conditionsthat intersect badlywithsocioeconomicstatus

•Stigmatization

Seniors (Medicare)andlow income(Medicaid)populationsareathigherriskof opioid misuse andabuse

Medicaid / •Medicaidbeneficiariesareprescribedopioidsattwicetherateofnon-Medicaidpatientsand areat3-6timestheriskofprescriptionpainkillersoverdose. 1
•Theprevalence ofdiagnosed opioidusedisorder amongMedicaidbeneficiariesis8.7per1000,compared to1outofevery1000patientscoveredwithcommercialinsurance2,3,4
Medicare / •Medicarebeneficiariesareprescribed opioidsattwicetheratefoundinthecommerciallyinsuredpopulation5
•Theprevalence ofdiagnosed opioidusedisorderamongMedicarebeneficiariesis6per1000,compared to1outofevery1000patientscoveredwithcommercialinsurance4

Sources:1)

2)

3)

4)

5)

RiskManagementIsaPackageDeal

•UseofPrescriptionDrugMonitoringProgram(PDMP)data

•Screeningandriskstratification

•ComplianceMonitoring

•Urinescreening

•Pill/Patchcounts

•Educationregardingdrugstorageandsharing

•Psychotherapyandhighly“structured”approaches

•Better/saferopioidproducts

PassikSD,KirshKL.Theinterfacebetweenpainanddrugabuseandtheevolutionofstrategiestooptimizepainmanagementwhile minimizingdrugabuse.ExperimentalandClinicalPsychopharmacology.2008;16(5):400-404.

OpioidRiskManagementToolsHaveComeaLongWay

•PDMP:

•Arethereotherprescribersof controlledsubstances?

•LC-MS/MSdrugtestingin24hours:

•Isthepatienttakingtheir prescribedmedication– nootherlicitor illicitopioids/substances?

•GeneticTesting:

•Isthepatienton thebestopioidfor them–mostlikelyto getbestresponseat mostreasonabledose?

•ScreeningTools:

•Ascertainrisklevelandprescribe appropriateopioiddeliverysystem(e.g.,ADFs)

•GivebackPrograms:

•Ensuresafedisposalanddecreaseopioidsavailablefor diversion

ResponsibilityforOptimalandSaferPainTreatmentsRestsWithManyStakeholders

Stakeholder / Role
Healthcareproviders / •Useriskassessmenttools
•Discussbenefitsand risks ofallappropriatemedicationclasseswithpatients
•Setappropriateguidelines and goalsof successfulopioidtherapytoensureexpectationsaroundopioid continuation
Patients / •Developand strictlyfollowa mutuallyagreed-upontreatmentplan withHCP
•Takemedicationonlyasprescribedwithout manipulatingthedeliverysystem(i.e., tampering)
Third-partypayors / •Beaccommodatingofdifferentlevelsofcarefor patientsbasedonrisks and thetoolsneededtopreventand/or treatmisuse,abuse, diversion,and addiction
•Needtomoveawayfrominadequately-monitored,drug-onlypain therapyfor themajorityof patientstreatedwithopioids
Lawenforcementandgovernmentregulators / •Allow stakeholders to combattheopioidepidemic
•Providereasonableaccessofnecessarytreatmentstopatientssufferingfromchronicpain
Pharmaceuticalindustry / •Developpotentiallysafer opioid products
•Conductmoreextensivepost-marketingstudies relatedtomisuse,abuse, diversion,and addiction
•Provideoversightof educationalprogramsfor presentationof fairandbalancedcontent
•Closelyobservesalestechniquestoascertaintheyfocus on providingopioids toonlyappropriatepatients
Media / •Raiseawareness oftheopioidepidemicwithout suggestingaddictionissolelya diseaseofexposure
•Avoidusingterms“addiction”and “physicaldependence”interchangeably
•Providemediacoveragetobothsuccesses and failures ofopioid pain managementinan accurateway

PassikSD.JOpioidManage;2017;13(6):391-396.

8

Third-PartyPayors

•Frequentvisits

•Urinedrugscreens

•Psychologicalcare

•Abusedeterrentopioids

•Lessdrugperprescription

JoransonDE.Arehealth-carereimbursementpoliciesabarriertoacuteandcancerpainmanagement?JournalofPainandSymptomManagement.1994;9(4):244-253.

Exampleof“RealWorld”CoverageDenial

FinalInternalAdverseBenefitDetermination:Afterconsideringallavailableevidence,previousdecisionsandyourmedication history,therecommendationistoupholdthedenial fortheprescriptiondrugXtampzaER(Oxycodone,extendedreleasecapsule).

Based on yourmedicalrecords,youarecurrentlytakingOxyContinandhastriedGabapentinand Percocetinthepast. However,yourprovider’sappealletterindicatesthereasoningforrequestingthenon-formularymedicationXtampzaERisthatXtampzaERhasthe mostabusedeterrenttechnologyon themarket.

According totheinformationreviewed,youarenotdemonstratingany drugabusebehaviorandhavenot failedcurrenttreatment

………and/orhavenottriedand failedallformularyoptionsavailabletotreatpain.Pleasenotethatifdrugabusebehavior isan issue,[PlanName]’sformularyprovidescoverageformany non-opioidpainmedications(asdescribedabove).

Payors’ReluctancetoCoverCostsoftheEntiretyoftheOpioidEpidemicisUnderstandable

•Payorsbearthecostsrelatedto:

•DrugTreatment

•Healthcare

•Disability

•Taxpayersbearthesocietalcostsrelatedto:

•CriminalJustice

•ChildServices

•Environmental

•Areweaskingpayorstomakeinvestmentsinsolvingsocialproblemsthattheycannotrecoup?

TheDisconnectedADFWorld

CourtesyofBobJones,CEOofAcuraPharmaceuticals

Passik’s5SuggestionsforImprovingOpioidSafety

1.Establish the “WellOpioidVisit”

•DevelopnextgenerationPDMPsoftware

2.Developnewtreatmentsforacutepaininyoungpeople

3.Limitshortactingopioidsforchronicpain

4.Eliminate morphinesulfateequivalent(MSE)limits foropioidstowhichtheydonotapply(i.e.,real-worldevidencesuggestsincreasedsafety)

•Acasefor tapentadolandbuprenorphinebeingconsideredexemptfromMSElimits

•Developa morespecificopioid-benzoMSEor have2 cutoffs:onefor patientsonbenzosandoneforthosenot onbenzos

5.Eliminate failfirstpoliciesforADFs

•Costsassociatedwithdiversionor tosociety(e.g., firstresponders,criminaljustice system,lossinproductivity) werenotincluded

•ADFs have the potentialto positivelyimpactopioidmisuse,abuse,andoverdose

•ICER concludedthatcostneutralitywouldbe achievedifADFs were discountedby41%fromtheir“currentmarket-basedprice”withoutallrelevantcostsincludedintheir model

•However,actualdiscountsoften exceed 41%

•Discountstogovernmentpayors(e.g.,stateMedicaid) often exceed 80%

SocietalCostSavingsfromAbuseDeterrent

FormulationsforPrescriptionOpioidsinCanada

140

120

100

80

60

40

20

0

EstimatedSocietalCosts(billionsinUSD)totheUSandCanadafrom 2012and2015

HealthcareCriminalJusticeProductivityCanadaUnitedStates

•Results:

•Medianreductioninnon-medicaluseratesbetween45.1-64%

•Theestimatedtotalsocietaleconomiccostswas

$17.1billionfrom2012to2015

•Themedianestimateofsocietalcostsavingswas$9.3billioninthesameperiod

•Conclusions:

•“Thedatasuggestthattheexpectedreductioninthenon-medicaluserateforprescription

Graphgeneratefrom dataincludedin:SkinnerB.SocietalcostsavingsfromabusedeterrentformulationsforprescriptionopioidsinCanada.CanadianHealthPolicy.2017.

opioidswouldresultfrommandatingadoptionofADFacrossallopioids,wouldverylikelyproducesignificantnetsocietalcostsavings.”

Governor’sWorkingGroup–OpioidRelatedDeathsin MA

•InMA,73%ofopioidrelateddeathsoccurredinpatientsonMedicareand/orMassHealthin2013and2014

•CommercialinsurersinMAremainunwillingtomakechangestotheircoverageuntiltheDFChasdeterminedtheirplan

ValueofADFOpioids

OralIngestion

OralChewing/Crushing

42%of oralabusersreportmanipulatingtablets1

Snorting

SmokingorSnortingHeroin

InjectingRxOpioids

InjectingHeroin

ButlerS,BlackR,FlemingAB.RelativeAbuseofCrush-ResistantPrescriptionOpioidTabletsviaAlternativeOralModesofAdministration.PainMedicine2017;0:1–15doi:10.1093/pm/pnx151. Open Access link:

ADFsAreAssociatedWithDecreasesinNonmedicalOpioidUseandOpioidAbuse

•IntroductionofADFs hasbeenassociatedwithdecreasesinratesof nonmedicaluseanddiversion1

•MedianADFeffectivenessof 45%to 64% reductioninnonmedicaluserates2

•Decreasesrangedfrom3%to99%dependingonmedicationandpatientpopulation2

•Declineof18%to23%inratesofdiagnosedabuse3

•Basedon ahypotheticalcohort model,ADFshave thepotentialtosubstantiallyreducetheincidenceof opioidabuserelative tonon-ADFs4

ADFandNon-ADFOpioids:BurdenofAbuseandAbuse-RelatedOutcomes*4

Outcome
(5-YearTimePeriod/100,000Patients) / ADFOpioids / Non-ADF
Opioids / Increment(ADF–Non-ADF)
Incidentabuse / 8229 / 10,532 / -2303
Person-yearsofabuse / 23,322 / 29,943 / -6621
Overdosedeaths / 1.38 / 1.77 / -0.39

*Cohortmodelof100,000patients withchronicpainwith ERopioidprescriptions.

1.GasiorM,etal.PostgradMed.2016;128(1):85-96.2. SkinnerBJ. CanadianHealthPolicy,May29,2017. 3.RossiterLF,etal.JMed Econ.2014;17(4):279-287.4. InstituteforClinicalandEconomicReview. Abuse Deterrent

FormulationsofOpioids:Effectivenessand Value.2017.

Tablereprintedwith permission fromInstituteforClinicalandEconomic Review.AbuseDeterrentFormulationsofOpioids:EffectivenessandValue.2017.

ADFsMakeupaSmall PercentoftheOpioidMarket

2017OpioidTRx Mix

EROpioidGenericvs.BrandMix

ADFvsNon-ADFBrandedERMix

90%

10%

75%

25%

79%

21%

ADFbrandsNon-ADFbrands

GenericERTRxBrandedERTRx

ImmediateRelease("IR")TRxExtendedRelease("ER")TRx

Source:IQVIAXponent 2017

OpioidMarket– PayorCoverage

OpioidMarket

(TotalLives:279,192,804)

CommercialMedicarePartDMedicaid

•Medicaidbeneficiariesrepresent23% ofthelives thatconsume(all)opioidprescriptionsintheUS

•However,Medicaidrepresentsjust3-6%oftotalADFprescriptions

•Despitehavingaccesstodiscountsof80%+offlistprice,theMedicaidchannelhasbeenslowtoadoptADFs

Source:IMSXponent,current52weeks;MMITasofJan2017

ThreecorebarrierspreventaccessanduptakeforADFs

Costtomanagedcareorganizationspreventsorlimitsaccess

  • Datashowshighlychallenging coverageforADFs,particularlyinMedicare,Medicaid
  • Wherecoverageexists,“failfirst”policiesthroughcheapergenericsaremajorobstacles

ADF

AccessUptakeBarriers

MisconceptionsaroundhowopioidsareabusedmarginalizeimportanceofADFs

  • Understandingroutesofabuse(oralvs.injection,snorting,crushing,chewing)
  • Understandingabuserpreferences forIRvs.ERformulations

Pharmacyaccessremainshighlychallenging

  • Justintimeinventorysystemsfornewdrugscanresultinabandonment
  • DEAandwholesalerallotmentsdissuade pharmaciesfromholdingnewproductsininventory

MisconceptionsofADFOpioids

•AllADFs arethesame / False
•No“real world”evidenceofdecreasingabuse / False
•Abusersjusttaketoo many pills(i.e.don’t manipulate) / Sometimes
•ADFsshouldbesavedfor“highrisk”patients / False
•ADFscan’tstopmostcommon methodof abuse(Oral) / Sometimes
•Limitingaccessto ER opioidswilldecreaseabuse / False

SignificantPayorEducationisRequired

Opioidprescribingisgoingdown whileoverdose deathsaregoingup–whoisnewlegislationhelping? Who isithurting?

CDC statistics:

BULLPENSLIDES

PrescribingRatesareDropping

CDCstatistics:

ButtheDeathRateKeepsClimbing

SourcesofDrugDiversion

•Diversionoflegitimatelyprescribedopioidproductsisarealconcern

•ADFtechnologiescanpreventdivertedmedicationsfrombeingmanipulatedforabuse,likelyresultinginbetteroutcomesforabusers

•Conclusions:“Ourresultssuggestthatself-treatmentofco-morbidpsychiatricdisturbancesisapowerfulmotivatingforcetoinitiateandsustainabuseofopioidsandthat theinitialsourceofdrugs

–aprescriptionofexperimentation–islargelyirrelevantintheprogressiontoasubstanceusedisorder”

Fig.1.TopfiftystemwordsprovidedbyRxandNon-RxRAPIDparticipantsinresponsetothequestion“Pleaselistthreewordsthatbestdescribehowopioidsmadeyoufeel?”Wordfrequenciesarerepresentedastagcloud(i.e.,thelargerthe word,themore frequentlyfoundinthedata).

Frequenciesrangedfrom0.40%to7.1%ofallanalyzedwords(Rx[N=198],Non-Rx[N=250]).

Fig.2.TopfiftystemwordsprovidedbyRxandNon-RxRAPIDparticipantsinresponsetothequestion“Inyourownwords,describeyourmotivationsforusingopioidsrightbeforeyouenteredyourfirsttreatmentprogramforopioidabuse.”Wordfrequenciesare representedastagcloud(i.e.,thelargertheword,themore frequentlyfoundinthedata).Frequenciesrangedfrom0.35%to3.3%ofallanalyzedwords(Rx[N=839],Non-

Rx[N =854]).

ADFsareAssociatedwithCostSavings

•IntroductionofADFshasalsobeenassociatedwithreductionsinmedicalandsocietalcosts1-4

AnnualCostSavings4

$1200

$1000

$800

$600

$400

$200

$0

1.GasiorM,etal.PostgradMed.2016;128(1):85-96.2. SkinnerBJ. CanadianHealthPolicy,May29,2017. 3.RossiterLF,etal.JMed Econ.2014;17(4):279-287.4. KirsonNY, et al.PainMed.2014;15:1450-1454.

Figurereprintedwithpermission fromKirsonNY,et al.PainMed. 2014;15:1450-1454.29

PotentialAvoidableSocietalCosts(CHPReport)

LimitShortActingOpioidsforChronicPain

•Preferencerelatedtoimmediacy/qualityof“high”andeaseofuse,particularlywhenmanipulatedfornon-oralabuse
•PayorprogramstoforceuseofIRopioidsvs.ADFERopioidsmayhaveunintentionalconsequences

Source:Cicero,TheodoreJ.et.Al.Relative preferencesintheabuseofimmediate-release versusextended-releaseopioidsinasampleoftreatment-seekingopioidabusers;PharmacoepidemiologyandDrugSafety,September4,2016