State-of-the-Science: Treatment of Neovascular Age-Related Macular Degeneration (AMD) Ivan J....

State-of-the-Science:State-of-the-Science:Treatment of NeovascularTreatment of Neovascular

Age-Related Macular Age-Related Macular Degeneration (AMD) Degeneration (AMD)

Ivan J. SuIvan J. Suñer, ñer, MDMDAssociate Professor of OphthalmologyAssociate Professor of Ophthalmology

Duke University Medical Center (Duke Eye Center)Duke University Medical Center (Duke Eye Center)Chief of Ophthalmology ServiceChief of Ophthalmology Service

Durham Veteran Affairs Medical CenterDurham Veteran Affairs Medical CenterDurham, NCDurham, NC

Presentation OutlinePresentation Outline Overview of age-related macular degeneration (AMD)Overview of age-related macular degeneration (AMD) Current therapies in the treatment of neovascular AMDCurrent therapies in the treatment of neovascular AMD

– Thermal laser photocoagulationThermal laser photocoagulation– Ocular photodynamic therapyOcular photodynamic therapy

VerteporfinVerteporfin– Vascular endothelial growth factor (VEGF) inhibitorsVascular endothelial growth factor (VEGF) inhibitors

FDA approvedFDA approved– PegaptanibPegaptanib– RanibizumabRanibizumab

Off labelOff label– BevacizumabBevacizumab

SummarySummary

Overview of Age-Related Macular Overview of Age-Related Macular Degeneration (AMD)Degeneration (AMD)

DefinitionDefinition

Late onset (age > 50 years)Late onset (age > 50 years)

Some degree of vision lossSome degree of vision loss

Lipid deposits (drusen) under retinaLipid deposits (drusen) under retina

EpidemiologyEpidemiology

15 million affected in the United States15 million affected in the United States Leading cause of vision loss age > 50 yearsLeading cause of vision loss age > 50 years Distribution (age)Distribution (age)

– 55–64: 17%55–64: 17%– 65–74: 26%65–74: 26%– >75: 42%>75: 42%

Congdon N, et al. Arch Ophthalmol. 2004;122:477.

Projected Prevalence of Advanced AMD* in Projected Prevalence of Advanced AMD* in the United Statesthe United States

0

1

2

3

2000 2020

Nu

mb

er o

f C

ases

Nu

mb

er o

f C

ases

(mil

lio

ns)

(mil

lio

ns)

YearYear

*Defined as neovascular AMD and/or geographic atrophy in at least 1 eye. Prevalence figures were calculated using 2000 US census data.

Friedman DS, et al. Arch Ophthalmol. 2004;122:564.

1.75

2.95

Photoreceptors

Choroid

RPE

Genentech, Inc. Data on file.

Normal RetinaNormal Retina

Fovea

Macula

Normal retina Bruch’s membrane thickens and drusen develop

Photoreceptors

Choroid

RPE

Fovea

Macula


Progression of AMDProgression of AMDDevelopment of DrusenDevelopment of Drusen

New abnormal blood vessels proliferate and penetrate Bruch’s

membrane

New blood vessels leak blood and fluid

Progression of AMDProgression of AMDFormation and Leakage from Choroidal Formation and Leakage from Choroidal

Neovascularization (CNV)Neovascularization (CNV)


Advanced Wet AMDAdvanced Wet AMDFibrovascular ScarFibrovascular Scar


Current Therapies in the Treatment of Current Therapies in the Treatment of Neovascular AMDNeovascular AMD

Thermal effects of laser Thermal effects of laser destroys CNV, low destroys CNV, low recurrence raterecurrence rate

Causes damage to Causes damage to surrounding healthy tissuesurrounding healthy tissue

Not for use on CNV located Not for use on CNV located beneath fovea (subfoveal)beneath fovea (subfoveal)

– Immediate, permanent Immediate, permanent decrease in central decrease in central visionvision

Laser beam Laser beam aimed at CNVaimed at CNV

Immediate damage to Immediate damage to RPE and photoreceptors RPE and photoreceptors

overlying CNVoverlying CNV

Thermal Laser PhotocoagulationThermal Laser Photocoagulation

CNV = choroidal neovascularization RPE = retinal pigment epithelium


VerteporfinVerteporfin

Intravenously administered photosensitizing drugIntravenously administered photosensitizing drug Attaches to the inner surface of abnormal proliferating Attaches to the inner surface of abnormal proliferating

blood vesselsblood vessels Activated by nonthermal laser light at 689 nmActivated by nonthermal laser light at 689 nm Generates highly reactive, short-lived oxygen radicals, Generates highly reactive, short-lived oxygen radicals,

which damage vessel wallswhich damage vessel walls Minimal effects on the surrounding tissue structuresMinimal effects on the surrounding tissue structures

Forms of SubfovealForms of SubfovealNeovascular AMDNeovascular AMD

Minimally classic Occult with no classicPredominantly classic

18%–24% 6%–19% 60%–75%

Olsen T, et al. Ophthalmology. 2004;111:250. Zawinka C, et al. Retina. 2005;25:324. Margherio RR, et al. Retina. 2000;20:325. Ng E, Adamis AP. Can J Ophthalmol. 2005;40:352.

67%

56%

49%39%

55%

45%

0102030405060708090

100

Predominantly Classic

12-Month Results of PDT Trials12-Month Results of PDT Trials TAP-VIP Study PopulationsTAP-VIP Study Populations

% P

atie

nts

Lo

sin

g <

15 L

ette

rs

PDT = photodynamic therapy.TAP Study Group. Arch Ophthalmol. 1999;117:1329. VIP Study Group. Am J Ophthalmol. 2001;131:541.*Azab M, et al. Arch Ophthalmol. 2005.

Minimally Classic Occult No Classic

PDTPlacebo

PDT benefit has been demonstrated for small lesions (<4 disc areas) of all compositions*

Endothelial cell activation, proliferation, migration4

VEGF-A Is a Key Mediator of Angiogenesis VEGF-A Is a Key Mediator of Angiogenesis

ANGIOGENESIS3 VASCULARLEAKAGE3

Environmental factors1

(hypoxia,2 pH)Growth factors,

hormones1 (EGF, bFGF, PDGF, IGF-1, IL-1, IL-6,

estrogen)

VEGF-A binding and activation

of VEGF receptor3

Endothelial cell

activation3

VEGF-A = vascular endothelial growth factor A; EGF = epidermal growth factor; bFGF = basic fibroblast

growth factor; PDGF = platelet-derived growth factor; lGF = insulin-like growth factor; IL= interleukin.

1. Dvorak HF. J Clin Oncol. 2002;20:4368. 2. Aiello LP, et al. Arch Ophthalmol. 1995;113:1538.

3. Ferrara N, et al. Nat Med. 2003;9:669. 4. Griffioen AW and Molema G. Pharmacol Rev. 2000;52:237.

Multiple Isoforms of VEGF-A Are Generated Multiple Isoforms of VEGF-A Are Generated from Exon Splicingfrom Exon Splicing

Adapted from Ferrara N, et al. Nat Med. 2003;9:669.

Highly diffusible isoform

1 121VEGF-A121

1 206

Highest molecular weight isoform bound to extracellular matrix

VEGFR-bindingdomain

Heparin-bindingdomain

VEGF-A206

Sequestered in the extracellular matrix

1 189VEGF-A189

1651

Most abundant isoform expressed in humans

VEGF-A165

VEGF Inhibition in AMDVEGF Inhibition in AMD

FDA approvedFDA approved PegaptanibPegaptanib

– AptamerAptamer– Specific for VEGF-A isoform 165Specific for VEGF-A isoform 16511

RanibizumabRanibizumab– Recombinant, humanized antibody fragmentRecombinant, humanized antibody fragment– Blocks all VEGF-A isoformsBlocks all VEGF-A isoforms

Off labelOff label BevacizumabBevacizumab

– Recombinant humanized monoclonal antibodyRecombinant humanized monoclonal antibody– Blocks all VEGF-A isoformsBlocks all VEGF-A isoforms

1Gragoudas ES, et al. N Engl J Med. 2004;351:2805.

Pegaptanib for Neovascular AMDPegaptanib for Neovascular AMDThe VISION StudyThe VISION Study

Concurrent, randomized, double-blind, controlled, dose-ranging studiesConcurrent, randomized, double-blind, controlled, dose-ranging studies– Prespecified combined data analysis Prespecified combined data analysis

1190 patients at 117 centers worldwide1190 patients at 117 centers worldwide– 295 received 295 received PegaptanibPegaptanib 0.3 mg0.3 mg– 298 received usual care with sham injections every 6 weeks298 received usual care with sham injections every 6 weeks

Photodynamic therapy with verteporfin was allowed per FDA-approved label at Photodynamic therapy with verteporfin was allowed per FDA-approved label at physician discretion for predominantly classic lesions in all treatment armsphysician discretion for predominantly classic lesions in all treatment arms

VISION = VEGF Inhibition Study in Ocular NeovascularizationGragoudas ES, et al. N Eng J Med. 2004;351:2805.

Pegaptanib 1.0 mg

IVT injection every IVT injection every 6 weeks6 weeks

Pegaptanib 0.3 mg

Pegaptanib 3.0 mg

UsualCare

Every 6 weeksEvery 6 weeks

68%75%

66%57%

53% 56%

010

20304050

607080

90100

Predominantly Classic Minimally Classic Occult No Classic

Pegaptanib 0.3 mgUsual Care

12-Month Results of Pegaptanib Trials12-Month Results of Pegaptanib Trials%

Pat

ien

ts L

osi

ng

<15

Let

ters

VISION Study: post-hoc analysis

Adapted from Gragoudas ES, et al. N Eng J Med. 2004;351:2805.

Two Pivotal Phase III Ranibizumab Two Pivotal Phase III Ranibizumab Trials in Neovascular AMDTrials in Neovascular AMD

MARINA = Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovasular AMD; ANCHOR = ANti-VEFG Antibody for the Treatment of Predominantly Classic CHORidal Neovascularization in AMD; VA visual acuity.

Presented at ARVO; April 30–May 4, 2006.

MARINA ANCHOR N 716 423

Lesion types Minimally classic Predominantlyor occult classic

Doses Placebo Placeboranibizumab 0.3 mg / ranibizumab 0.5 mg ranibizumab 0.3 mg / ranibizumab 0.5 mg

Primary endpoint % patients losing <15 letters at month 12

Key secondary Mean change from baseline in VAEndpoints over time up to month 12 ≥15-letter gainers in VA at month 12

compared to baseline

Mean change in leakage at month 12 compared to baseline

MARINA Trial: Primary EndpointMARINA Trial: Primary EndpointPatients Losing <15 Letters from Baseline at Month 12Patients Losing <15 Letters from Baseline at Month 12

*P < .0001 vs ShamPresented at ARVO; April 30–May 4, 2006.

0

10

20

30

40

50

60

70

80

90

100

Sham(n = 238)

Ranibizumab 0.3 mg(n = 238)


94.6%*94.5%*

% o

f S

ub

ject

s

62.2%

Maintains Vision

Secondary Endpoint:Secondary Endpoint:Mean Change in Visual Acuity Over TimeMean Change in Visual Acuity Over Time

Improves Vision

ET

DR

S L

ette

rs

17.7-letter difference*

17.0-letter difference*

*P < .0001 vs Sham

Sham (n = 238) Ranibizumab 0.3 mg (n = 238) Ranibizumab 0.5 mg (n = 240)

1 2 3 4 5 6 7 8 9 10 11 12

-15

-10

-5

0

5

10

15

0-10.5

+6.5

+7.2


Months

ANCHOR Trial: Primary EndpointANCHOR Trial: Primary EndpointSubjects Losing <15 Letters from Baseline at Month 12Subjects Losing <15 Letters from Baseline at Month 12

*P < .0001 vs PDT

0

10

20

30

40

50

60

70

80

90

100

PDT(n = 143)



96.4%*94.3%*

% o

f S

ub

ject

s

64.3%

Maintains VisionPresented at ARVO; April 30–May 4, 2006.

ET

DR

S L

ette

rs

Improves Vision

Secondary Endpoint:Secondary Endpoint:Mean Change in Visual Acuity Over TimeMean Change in Visual Acuity Over Time

Note: Vertical bars are ± one standard error of the mean.

*P < .0001 vs Sham

+11.3

+8.5

–9.5

20.8-letterdifference*

18.0-letterdifference*

PDT (n = 143) Ranibizumab 0.3 mg (n = 140) Ranibizumab 0.5 mg (n = 139)

Month-15

-10

-5

0

5

10

15

1 2 3 4 5 6 7 8 9 10 11 12


Investigational Bevacizumab TrialsInvestigational Bevacizumab Trials

California Retina Consultants Study. Avery RL et al. Ophthalmology. 2006 Mar. Vitreous Retina Macula Consultants of New York. Spaide RF et al. Retina. 2006 Apr.

Preliminary data from 2 trials show promising Preliminary data from 2 trials show promising decrease in central macular thicknessdecrease in central macular thickness

Both trials reported a mean improvement in visual Both trials reported a mean improvement in visual acuity with bevacizumabacuity with bevacizumab

Follow-up too short to make treatment Follow-up too short to make treatment recommendationsrecommendations

Further study neededFurther study needed

SummarySummary

Neovascular AMD is leading cause of legal blindness Neovascular AMD is leading cause of legal blindness in patients > 50 years old in the United Statesin patients > 50 years old in the United States

Thermal laser photocoagulation effective in Thermal laser photocoagulation effective in juxta- and extra-foveal lesions (<10%)juxta- and extra-foveal lesions (<10%)

Ocular photodynamic therapy (OPT) approved for Ocular photodynamic therapy (OPT) approved for predominantly classic choroidal neovascularization predominantly classic choroidal neovascularization (~20% of subfoveal)(~20% of subfoveal)

SummarySummary

Vascular endothelial growth factor (VEGF) inhibition is Vascular endothelial growth factor (VEGF) inhibition is effective in all forms of subfoveal choroidal neovascularization effective in all forms of subfoveal choroidal neovascularization – FDA approvedFDA approved

PegaptanibPegaptanib RanibizumabRanibizumab

– Off labelOff label BevacizumabBevacizumab

VEGF inhibition therapy with ranibizumab VEGF inhibition therapy with ranibizumab – 95% response rate95% response rate– On average, visual acuity improvesOn average, visual acuity improves

Implications of Anti-VEGFImplications of Anti-VEGFTherapies in Managed Care:Therapies in Managed Care:

Avoiding Billing PitfallsAvoiding Billing Pitfalls

Alexander M. Stockdale, MBAAlexander M. Stockdale, MBA

Chief Executive Officer Chief Executive Officer Southeastern Retina AssociatesSoutheastern Retina Associates

Knoxville, TNKnoxville, TN

Avoiding Billing PitfallsAvoiding Billing Pitfalls Understand Medicare competitive acquisition program Understand Medicare competitive acquisition program

(CAP) versus “buy and bill”(CAP) versus “buy and bill”1,21,2

Analyze past performance/problemsAnalyze past performance/problems Know your specific carrier rules, advance beneficiary Know your specific carrier rules, advance beneficiary

notices (ABNs)notices (ABNs)33

Educate and update MDs, staff, patientsEducate and update MDs, staff, patients Use programs and resources of manufacturers when Use programs and resources of manufacturers when

appropriateappropriate Work cooperatively with carriers for coverage and Work cooperatively with carriers for coverage and

flexibilityflexibility

1. Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/Competitive AcquisforBios/Downloads/303d.pdf1. Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/Competitive AcquisforBios/Downloads/303d.pdf2. Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/CompetitiveAcquisforBios/02_infophys.asp.2. Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/CompetitiveAcquisforBios/02_infophys.asp.

Accessed June 27, 2006.Accessed June 27, 2006.3. Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/BNI. Accessed June 27, 2006.3. Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/BNI. Accessed June 27, 2006.

CAPCAP

For Part B Drugs and BiologicalsFor Part B Drugs and Biologicals11

Does not apply to drugs under Medicare Does not apply to drugs under Medicare Prescription Drug BenefitPrescription Drug Benefit1,21,2

American Academy of Ophthalmology (AAO) American Academy of Ophthalmology (AAO) pushed to include pegaptanib and verteporfin; pushed to include pegaptanib and verteporfin; ranibizumab will follow in 2007ranibizumab will follow in 2007

Only 1 CAP pharmacy provider signed upOnly 1 CAP pharmacy provider signed up Off to bad startOff to bad start

1. Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/MedicareGenInfo. Accessed June 27, 2006.1. Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/MedicareGenInfo. Accessed June 27, 2006.2. Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/MMAUpdate/downloads/PL108–1732. Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/MMAUpdate/downloads/PL108–173

summary.pdf. Accessed June 27, 2006.summary.pdf. Accessed June 27, 2006.

Under CAPUnder CAP

Physicians can choose to obtain drugs from Physicians can choose to obtain drugs from Medicare-approved pharmaciesMedicare-approved pharmacies

Drugs are shipped directly from pharmacies to Drugs are shipped directly from pharmacies to physiciansphysicians

Billing is handled by pharmacy but practices Billing is handled by pharmacy but practices may still have to collect copays, etc.may still have to collect copays, etc.

Under CAPUnder CAP

Physicians charge professional fee onlyPhysicians charge professional fee only Practices do have to cooperate with CAP Practices do have to cooperate with CAP

pharmacies for informationpharmacies for information11

Still have buy and bill for non-Medicare patientsStill have buy and bill for non-Medicare patients 14-day claim submission deadline – YIKES!14-day claim submission deadline – YIKES!

1. Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/Competitive 1. Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/Competitive AcquisforBios/Downloads/303d.pdf. Accessed June 27, 2006.AcquisforBios/Downloads/303d.pdf. Accessed June 27, 2006.

Why Would Physicians Choose CAP?Why Would Physicians Choose CAP?11

For Medicare patients, eliminates uncertainty of paymentFor Medicare patients, eliminates uncertainty of payment Not as great a need to provide stock levels or keepNot as great a need to provide stock levels or keep

track of orderingtrack of ordering Fear of large debt for drug, and of collection problemsFear of large debt for drug, and of collection problems Easier? Easier? CAP attractive for some regionsCAP attractive for some regions

(eg, South Carolina tax issue)(eg, South Carolina tax issue)

1. Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/Competitive 1. Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/Competitive AcquisforBios/Downloads/303d.pdf. Accessed June 27, 2006.AcquisforBios/Downloads/303d.pdf. Accessed June 27, 2006.

Experience with Commercial CAPExperience with Commercial CAP

Paperwork onerousPaperwork onerous Confusing to patientsConfusing to patients Have to loan drug Have to loan drug More difficult and time consuming thanMore difficult and time consuming than

buy and billbuy and bill No payment for handling and paperworkNo payment for handling and paperwork

Experience with Buy and BillExperience with Buy and Bill11

MDs choose when to treat patient—no delay MDs choose when to treat patient—no delay waiting for drug waiting for drug

Medicare billing and payment is smooth and Medicare billing and payment is smooth and rapid—commercials generally OK in time rapid—commercials generally OK in time

Drug margin helps cover shipping, handling, Drug margin helps cover shipping, handling, and billing costsand billing costs

1. Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/CompetitiveAcquisforBios/02_infophys.asp. 1. Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/CompetitiveAcquisforBios/02_infophys.asp. Accessed June 27, 2006.Accessed June 27, 2006.

Analyze Past ExperienceAnalyze Past Experience FDA-approved therapiesFDA-approved therapies

– Photodynamic therapy (PDT)Photodynamic therapy (PDT)– PegaptanibPegaptanib

Non-FDA-approved therapiesNon-FDA-approved therapies– Intravitreal triamcinoloneIntravitreal triamcinolone– BevacizumabBevacizumab

Combined therapiesCombined therapies Payment and billing problemsPayment and billing problems

– In-office confusionIn-office confusion– Insurance coverageInsurance coverage– Treatment of associated charges for Evaluation and Management Treatment of associated charges for Evaluation and Management

(E/M)(E/M)11 and diagnostic tests and diagnostic tests

1. Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/MLNProducts/downloads/1. Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/MLNProducts/downloads/eval_mgmt_serv_guide.pdf. Accessed June 27, 2006.eval_mgmt_serv_guide.pdf. Accessed June 27, 2006.

Patient Population for AMDPatient Population for AMD

Varies by state, insurance carriers, demographicsVaries by state, insurance carriers, demographicsBut:But:

Vast majority of patients are pure MedicareVast majority of patients are pure MedicareOr:Or:– Medicare HMO patients Medicare HMO patients – Commercial patientsCommercial patients– Medicaid/managed MedicaidMedicaid/managed Medicaid– Uninsured/underinsuredUninsured/underinsured

Importance of ABNsImportance of ABNs

Patients need to be fully informed and awarePatients need to be fully informed and aware Staff training and accountabilityStaff training and accountability MD knowledgeMD knowledge ReimbursementReimbursement ComplianceCompliance

ABNs = advanced beneficiary noticesABNs = advanced beneficiary notices

Sample AMD Coverage MatrixSample AMD Coverage Matrix

PDT = photodynamic therapy; IVT = intravitreal triamcinolone.

InsuranceType PDT PDT/IVT Pegaptanib IVT Ranibizumab Bevacizumab Notes

Medicare Yes Yes/50% Yes Yes Yes Yes Bevacizumabafter failureof therapy

MedicareHMO 1 Yes Yes/50% Yes Yes No No 2 OCT limit

Medicare HMO 2 Yes No Yes No Yes Yes Precert

CommercialInsurance 1 Yes Yes/50% Yes Yes Yes No

CommercialInsurance 2 Yes No Yes No No Yes Precert

Medicaid Yes Yes/50% Yes Yes Yes No

Successful Billing BasicsSuccessful Billing Basics

Staff coordination and educationStaff coordination and education Report problems centrallyReport problems centrally Note trends Note trends Update matrixUpdate matrix Take advantage of manufacturer resourcesTake advantage of manufacturer resources

Financial Good HousekeepingFinancial Good Housekeeping

Good inventory procedures and accountabilityGood inventory procedures and accountability Rotate stock of drugsRotate stock of drugs Good clinical practices with staffGood clinical practices with staff

– Don’t open drug until MD/patient makes Don’t open drug until MD/patient makes final treatment decisionfinal treatment decision

Seek replacement drug when appropriateSeek replacement drug when appropriate

AMD Treatment CollectionsAMD Treatment Collections

Relative collections per treatment typeRelative collections per treatment type Staff timeStaff time Buy and bill practice or CAPBuy and bill practice or CAP SuppliesSupplies PDT laser and infusion maintenance cost PDT laser and infusion maintenance cost

assessed per caseassessed per case Diagnostic and E/M differencesDiagnostic and E/M differences

Collections by Treatment TypeCollections by Treatment Type

0

100

200

300

400

500

600

Bevacizumab PDT Pegaptanib Ranibizumab PDT/IVK PDT/IVK

PDT = photodynamic therapy; IVT = intravitreal triamcinolone.

Patient Cost EducationPatient Cost Education

Avoid discussion of cost in lanesAvoid discussion of cost in lanes Instead refer to billing personInstead refer to billing person ABN responsibility of clinical staffABN responsibility of clinical staff Billing person needs tools to answer intelligentlyBilling person needs tools to answer intelligently

– Fee schedules (including self-pay)Fee schedules (including self-pay)– Coverage matrixCoverage matrix– Decision-making ability within guidelinesDecision-making ability within guidelines– Understanding of manufacturing support programsUnderstanding of manufacturing support programs

Manufacturer ResourcesManufacturer Resources

For FDA-approved drugs and applicationsFor FDA-approved drugs and applications Direct-sales personDirect-sales person Retinal business/reimbursement managerRetinal business/reimbursement manager Assistance programsAssistance programs

– Copay assistance foundationsCopay assistance foundations– Uninsured and noninsured drug programsUninsured and noninsured drug programs

Insurance CarriersInsurance Carriers

Know and communicate with decision makers about Know and communicate with decision makers about AMD therapiesAMD therapies

Make sure they get latest data ASAPMake sure they get latest data ASAP Work cooperatively with manufacturers’ representatives Work cooperatively with manufacturers’ representatives

as appropriate to seek drug approvalas appropriate to seek drug approval Be thorough, insistent, and consistent as patient’s Be thorough, insistent, and consistent as patient’s

advocateadvocate

Implications of Anti-VEGF Therapies Implications of Anti-VEGF Therapies in Managed Care: in Managed Care:

Reimbursement StrategiesReimbursement Strategies

Kirk A. Mack, COE, CPC, COMTKirk A. Mack, COE, CPC, COMT

Senior ConsultantSenior ConsultantCorcoran Consulting GroupCorcoran Consulting Group

San Bernardino, CASan Bernardino, CA

Intravitreal Injection ReimbursementIntravitreal Injection Reimbursement

Medicare utilizationMedicare utilization Medicare reimbursementMedicare reimbursement Antiangiogenic therapyAntiangiogenic therapy Medicare coverage of off-label drugsMedicare coverage of off-label drugs Medicare coverage of ranibizumabMedicare coverage of ranibizumab Medicare coverage of allied servicesMedicare coverage of allied services Chart documentationChart documentation

Top 10 Ophthalmic ProceduresTop 10 Ophthalmic ProceduresMedicare Utilization Patterns (18 - Ophthalmology)Medicare Utilization Patterns (18 - Ophthalmology)

RankRank CPTCPTCodeCode ProcedureProcedure RankRank CPTCPT

CodeCode ProcedureProcedure

11 6698466984 Cataract w/IOLCataract w/IOL 66 6585565855 Laser TrabeculoplastyLaser Trabeculoplasty

22 6682166821 YAG CapsulotomyYAG Capsulotomy 77 6722167221 PDTPDT

33 6876168761 Punctal Occlusion Punctal Occlusion plugsplugs 88 6722867228 PRPPRP

44 6782067820 Epilation LashesEpilation Lashes 99 6676166761 IridotomyIridotomy

55 6721067210 Focal LaserFocal Laser 1010 6702867028 Intravitreal InjectionIntravitreal Injection

CPT = current procedural terminology; IOL = intraocular lens; YAG = yttrium aluminum garnet; PDT = photodynamic therapy; PRP = panretinal photocoagulation.

Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/MedicareMedicaidStatSuppl/ Accessed July 20, 2006

Medicare Utilization Medicare Utilization

67028 Intravitreal Injection

0

50000

100000

150000

200000

250000

300000

1998 1999 2000 2001 2002 2003 2004 2005

Year

From Eyetech IOQ reports. Available at: http://www.eyetech.net

Proc

edur

es

Part B Growth in ServicesPart B Growth in Services

Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/NonIdentifiableDataFiles/03_PartBExactSummarySystem.asp. Accessed July 20, 2006

ServicesServices ServicesServices

Intravitreal injectionIntravitreal injection 92%92% Fundus photographyFundus photography 9%9%

PachymetryPachymetry 42%42% Fluorescein angiographyFluorescein angiography 8%8%

Scanning laserScanning laser 26%26% Extended Extended ophthalmoscopy ophthalmoscopy

7%7%

PDTPDT 19%19% Glaucoma lasersGlaucoma lasers 7%7%

B-scanB-scan 18%18% A-scan biometryA-scan biometry 7%7%

PPVPPV 10%10% Outpatient consultationsOutpatient consultations 6%6%


Medicare utilization Medicare utilization Medicare reimbursementMedicare reimbursement

Medicare Reimbursement Medicare Reimbursement Intravitreal Injection (67028)Intravitreal Injection (67028)

Participating surgeon, non-facility rateParticipating surgeon, non-facility rate $202.75$202.75 Participating surgeon, facility rateParticipating surgeon, facility rate $155.38$155.38 Non-par surgeon, non-facility rateNon-par surgeon, non-facility rate $192.61$192.61 Non-par surgeon, facility rateNon-par surgeon, facility rate $147.61$147.61 Non-par surgeon, limiting chargeNon-par surgeon, limiting charge $221.51$221.51

Separate payment for the injected agentSeparate payment for the injected agent

Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/PhysicianFeeSched/Accessed July 20, 2006


Medicare utilization Medicare utilization Medicare reimbursementMedicare reimbursement Antiangiogenic therapyAntiangiogenic therapy

Intravitreal Injections for Wet AMDIntravitreal Injections for Wet AMDAnti-VEGF AgentsAnti-VEGF Agents

Antiangiogenic therapyAntiangiogenic therapy Pegaptanib Pegaptanib

– Dec 2004, for neovascular (wet) AMDDec 2004, for neovascular (wet) AMD BevacizumabBevacizumab

– For metastatic colorectal cancerFor metastatic colorectal cancer RanibizumabRanibizumab

– June 2006, for neovascular (wet) AMDJune 2006, for neovascular (wet) AMD

AMD = age-related macular degeneration; VEGF = vascular endothelial growth factor.

Intravitreal Injections for Wet AMDIntravitreal Injections for Wet AMDAnti-VEGF AgentsAnti-VEGF Agents

Antiangiogenic therapyAntiangiogenic therapy PegaptanibPegaptanib

– On-labelOn-label BevacizumabBevacizumab

– Off-label Off-label RanibizumabRanibizumab

– On-labelOn-label

Pegaptanib Pegaptanib (Pegaptanib Sodium Injection)(Pegaptanib Sodium Injection)

J2503* – injection, pegaptanib sodium, 0.3 mg J2503* – injection, pegaptanib sodium, 0.3 mg Payment based on ASP + 6%Payment based on ASP + 6%

– ASP updated quarterlyASP updated quarterly Widespread coverage by Medicare and other payersWidespread coverage by Medicare and other payers

*Use C9128 in hospital setting; same payment:

Since 1/1/06, J2503 replaces J3490 on claims

ASP = average sale price.


Medicare utilization Medicare utilization Medicare reimbursementMedicare reimbursement Antiangiogenic therapyAntiangiogenic therapy Medicare coverage of off-label drugsMedicare coverage of off-label drugs

Unlabeled Use of DrugUnlabeled Use of Drug

““If a medication is determined not to be reasonable and If a medication is determined not to be reasonable and necessary for diagnosis or treatment of an illness or injury necessary for diagnosis or treatment of an illness or injury according to these guidelines, the carrier excludes the entire according to these guidelines, the carrier excludes the entire charge (i.e., for both the drug and its administration). Also, charge (i.e., for both the drug and its administration). Also, carriers exclude from payment any charges for other services carriers exclude from payment any charges for other services (such as office visits) which were primarily for the purpose of (such as office visits) which were primarily for the purpose of administering a noncovered injection (i.e., an injection that is administering a noncovered injection (i.e., an injection that is not reasonable and necessary for the diagnosis or treatment of not reasonable and necessary for the diagnosis or treatment of an illness or injury). . . ”an illness or injury). . . ”

Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/manuals/Downloads/bp102c15.pdf Accessed July 20, 2006

Drug Coverage CriteriaDrug Coverage Criteria

Were standard, accepted treatments, including approved drugs, Were standard, accepted treatments, including approved drugs, tried or contraindicated before considering a drug for an off-label tried or contraindicated before considering a drug for an off-label use?use?

Do any of the major drug compendia and related peer-reviewed Do any of the major drug compendia and related peer-reviewed scientific articles support the off-label use (MCM 2049.1)?scientific articles support the off-label use (MCM 2049.1)?

Do any specialty society publications recommend this off-label Do any specialty society publications recommend this off-label use?use?

Is this off-label use an accepted standard of medical practice?Is this off-label use an accepted standard of medical practice? Is authoritative medical literature available to support this use? Is authoritative medical literature available to support this use?

Are the level of evidence, endpoint measured, and number of Are the level of evidence, endpoint measured, and number of patients adequate (MCM 2049.C.3)? patients adequate (MCM 2049.C.3)?

Intravitreal Injection of BevacizumabIntravitreal Injection of Bevacizumab

““Off-label” use when injected in the eyeOff-label” use when injected in the eye– Neovascular age-related macular degenerationNeovascular age-related macular degeneration– Clinically significant macular edemaClinically significant macular edema– Macular edema from Central retinal vein occlusionMacular edema from Central retinal vein occlusion

Vigorous informed consent needed Vigorous informed consent needed – ““Off-label” statusOff-label” status– Absence of controlled trials studies for ophthalmic useAbsence of controlled trials studies for ophthalmic use

Intravitreal Injection of BevacizumabIntravitreal Injection of Bevacizumab

Utilize an Advance Beneficiary Notice (ABN)Utilize an Advance Beneficiary Notice (ABN) CodingCoding

– 67028 GA – intravitreal injection*67028 GA – intravitreal injection*– J3490 GA – unclassified drug (rather than J9035) J3490 GA – unclassified drug (rather than J9035)

Description of drug in comment field (box 19)Description of drug in comment field (box 19)

*Some Medicare carriers require 67299-GA.

Advance Beneficiary NoticeAdvance Beneficiary Notice

Items or services:Items or services: Intravitreal injection of Intravitreal injection of bevacizumabbevacizumab for for the treatment of neovascular (wet) age-related macular the treatment of neovascular (wet) age-related macular degeneration (AMD)degeneration (AMD)

Because:Because: Medicare’s Benefit Policy Manual does not usually Medicare’s Benefit Policy Manual does not usually cover use of a drug that is not included as an indication on cover use of a drug that is not included as an indication on the drug’s label as approved by the FDA. While there are the drug’s label as approved by the FDA. While there are exceptions to this general prohibition, use of bevacizumab exceptions to this general prohibition, use of bevacizumab to treat wet AMD is off-label, investigational, experimental to treat wet AMD is off-label, investigational, experimental and noncoveredand noncovered

Intravitreal Injection of Bevacizumab Intravitreal Injection of Bevacizumab Limited Medicare CoverageLimited Medicare Coverage

BC/BS MontanaBC/BS Montana CIGNA (ID, NC, TN)CIGNA (ID, NC, TN) Empire (NY, NJ)Empire (NY, NJ) First Coast (CT, FL)First Coast (CT, FL) NHIC (New England)NHIC (New England) Noridian (Rocky Mountains)Noridian (Rocky Mountains) Wisconsin Physician Services (MN, WI, MI, IL)Wisconsin Physician Services (MN, WI, MI, IL)

Coverage at the discretion of the local carrierCoverage at the discretion of the local carrier


Medicare utilization Medicare utilization Medicare reimbursementMedicare reimbursement Antiangiogenic therapyAntiangiogenic therapy Medicare coverage of off-label drugsMedicare coverage of off-label drugs Medicare coverage of ranibizumabMedicare coverage of ranibizumab

Medicare policies are in the process Medicare policies are in the process of being published for intravitreal of being published for intravitreal injection of ranibizumabinjection of ranibizumab

RanibizumabRanibizumab


FDA approval June 30, 2006FDA approval June 30, 200611

J3590 J3590 Unclassified biologicsUnclassified biologics Description in comment field (box 19)Description in comment field (box 19) Treatment of wet AMD (362.52)Treatment of wet AMD (362.52)

1http://www.fda.gov/bbs/topics/NEWS/2006/NEW01405.html

Utilize an Advance Beneficiary Notice (ABN)Utilize an Advance Beneficiary Notice (ABN) Coding Coding

– 67028 GA – intravitreal injection*67028 GA – intravitreal injection*– J3590 GA – unclassified biologicsJ3590 GA – unclassified biologics

Description of drug in comment field (box 19)Description of drug in comment field (box 19)


Reimbursement unknown at this timeReimbursement unknown at this time– Usually, Average Selling Price (ASP) + 6%Usually, Average Selling Price (ASP) + 6%

Transmittal 528; Change Request 3783 (effective 7/1/2005)



Medicare utilization Medicare utilization Medicare reimbursementMedicare reimbursement Antiangiogenic therapyAntiangiogenic therapy Medicare coverage of off-label drugsMedicare coverage of off-label drugs Medicare coverage of ranibizumabMedicare coverage of ranibizumab Medicare coverage of allied servicesMedicare coverage of allied services

Minor SurgeryMinor Surgery

Reimbursed care during global periodReimbursed care during global period Diagnostic tests Diagnostic tests Exams or consultationsExams or consultations

– Same day, unrelated diagnosis (-25)Same day, unrelated diagnosis (-25)– Same day, separately identifiable (-25)Same day, separately identifiable (-25)– Postoperative, unrelated Evaluation and Management Postoperative, unrelated Evaluation and Management

services (-24)services (-24) Staged procedure (-58)Staged procedure (-58)

Centers for Medicare & Medicaid Services. Available at: http://www.cms.hhs.gov/manuals/downloads/clm104c12.pdf Accessed July 20, 2006

Diagnostic Tests for AMDDiagnostic Tests for AMD

92135 — optical coherence tomography (OCT)92135 — optical coherence tomography (OCT)– Retina indications vary by carrierRetina indications vary by carrier11

92250 — fundus photography 92250 — fundus photography 92235 — fluorescein angiography92235 — fluorescein angiography 92240 — indocynanine green angiography (ICG)92240 — indocynanine green angiography (ICG)

1 Check specific carrier to determine if policy includes expanded retina indications.

Screening Tests for AMDScreening Tests for AMD

MacuScopeMacuScope Preferential hyperacuity perimetry (PHP)Preferential hyperacuity perimetry (PHP)

Billing Office Visit Billing Office Visit with Minor Procedurewith Minor Procedure

Evaluation and Management Service Resulting in the Evaluation and Management Service Resulting in the Initial Decision to Perform SurgeryInitial Decision to Perform Surgery

““...where the decision to perform the minor procedure is ...where the decision to perform the minor procedure is typically done immediately before the service, it is typically done immediately before the service, it is considered a routine preoperative service and a visit or considered a routine preoperative service and a visit or consultation is not billed in addition to the procedure.”consultation is not billed in addition to the procedure.”


Billing Office Visit Billing Office Visit with Minor Procedurewith Minor Procedure

CPT Modifier 25 — Significant Evaluation and CPT Modifier 25 — Significant Evaluation and Management Service By Same Physician On Date of Management Service By Same Physician On Date of Global ProcedureGlobal Procedure

Pay for an evaluation and management service provided on Pay for an evaluation and management service provided on the day of a procedure with a global fee period if the the day of a procedure with a global fee period if the physician indicates that the service is for a significant, physician indicates that the service is for a significant, separately identifiable evaluation and management service separately identifiable evaluation and management service that is above and beyond the pre- and post-operative work that is above and beyond the pre- and post-operative work of the procedure.of the procedure.


Modifier -25Modifier -25

Significant separateSignificant separate Evaluation and Management Evaluation and Management services services on the dayon the day of a of a minorminor surgery surgery

ie, ie, to cope with disease in both eyesto cope with disease in both eyes

9201292012-25*-25* 362.52 AMD OU362.52 AMD OU6702867028 362.52 AMD OS362.52 AMD OS

*Some carriers do not want modifier on new-patient exams.

Operative ReportOperative Report

Indications for surgeryIndications for surgery Description of the procedureDescription of the procedure Manner in which surgery performed Manner in which surgery performed Preop and postop diagnosesPreop and postop diagnoses Discharge instructionsDischarge instructions

Executive SummaryExecutive Summary

Extraordinary growth of procedure volumeExtraordinary growth of procedure volume Plan for a lot more intravitreal injectionsPlan for a lot more intravitreal injections Several anti-VEGF agents; ranibizumab is the latestSeveral anti-VEGF agents; ranibizumab is the latest Off-label use per se does not exclude coverageOff-label use per se does not exclude coverage Coverage depends on standard of careCoverage depends on standard of care Use an ABN; beneficiary is financially responsibleUse an ABN; beneficiary is financially responsible Document informed consent and operative reportDocument informed consent and operative report

State-of-the-Science: Treatment of Neovascular Age-Related Macular Degeneration (AMD) Ivan J....

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