REFERENCES1. Hu Y, et al. Immunology 2009;128:260-70. 2. Weber MS, Hemmer B. Results Probl Cell Differ 2010;51:115-26. 3. Havari E, et al. Immunology 2014;141:123-31. 4. Cox AL, et al. Eur J Immunol 2005;35:3332-42. 5. Coles AJ, et al. N Engl J Med 2008;359:1786-801. 6. Cohen JA, et al. Lancet 2012;380:1819-28. 7. Coles AJ, et al. Lancet 2012;380:1829-39. 8. Graves J, et al. Neurology 2013;30 (abstract P3.158). 9. Fox EJ, et al. Neurology 2013;30 (abstract S41.001).

CONCLUSIONS• Interim data from the CARE-MS II extension study demonstrate that alemtuzumabhasdurableefficacyondisabilitythrough3yearsinpatientswhohadrelapsedonpriortherapy,despitethemajorityofpatientsreceivingnoadditionalalemtuzumabtreatmentcoursesorotherDMTs – AlmosthalfofalemtuzumabpatientsdemonstratedimproveddisabilityscoresatYear3comparedwiththatatstudybaseline

– Morethanonethirdofformeralemtuzumabpatientsattainedsustaineddisabilityimprovement(6-monthsustainedreductionindisability) by Year 3

– Similardisabilityoutcomeswereobservedinpatientswhoreceivedonly 2 treatment courses over 3 years

• Thesefindings,togetherwithpreviouslyreporteddata,supportthepositivebenefit-riskprofileforalemtuzumabasapotentialtreatmentforRRMSinpatientswhorelapsedonpriortherapy

INTRODUCTION• AlemtuzumabisahumanizedmonoclonalantibodyapprovedinAustralia,Brazil,Canada,theEuropeanUnion,andMexicoforthetreatmentofactiverelapsing-remittingmultiplesclerosis(RRMS)thatselectivelytargetsCD52,resultingindepletionandsubsequentrepopulationofcirculatingTandBlymphocytes1-4

• Alemtuzumab,administeredin2annualcourses,hasdemonstratedsuperiorefficacyvs.high-dosesubcutaneousinterferonbeta-1a(SCIFNB-1a)intreatment-naiveRRMSpatients(CAMMS223[NCT00050778];ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis[CARE-MS]I[NCT00530348])5,6;andinpatientswhorelapsedonapriortherapy(CARE-MSII[NCT00548405])7 – Intheseclinicaltrials,alemtuzumabhadaconsistentandmanageablesafetyprofile,withthemostcommonadverseevents(AEs)beinginfusion-associatedreactions,non-serious infections, and autoimmune AEs

• InCARE-MSII,alemtuzumabsignificantlyreduced6-monthsustainedaccumulationofdisabilityat2yearsby49%beyondthatwithSCIFNB-1a(p<0.0001),andalemtuzumabpatientsweremorethantwiceaslikelytodemonstrate6-monthsustainedimprovementinpreexistingdisability(hazardratio2.57;p=0.0002)7 – PatientstreatedwithalemtuzumabalsohadsignificantlyimprovedvisualoutcomesusingSloanlow-contrastacuitymetrics,andfunctionaloutcomesusingMultipleSclerosisFunctionalComposite,comparedwithSCIFNB-1aatYear2(p<0.05)7,8

OBJECTIVE• ThepresentstudyexaminedthedurabilityofdisabilityimprovementinYear3follow-upduringanongoingextensionstudy(NCT00930553)ofalemtuzumabpatientswhorelapsedonapriortherapy

METHODSStudy DesignCore Study7

• CARE-MSIIwasarandomized,rater-blinded,active-controlled,head-to-head,phase3trial of 24 months’ duration

• Entrycriteriaincludedage18–55years,baselineExpandedDisabilityStatusScale(EDSS)score ≤5,MSsymptomonsetwithin10years,activeRRMS(≥2relapsesinprior2yearsand ≥1intheprioryear),andrelapseonpriortherapy(≥1relapseduringtreatmentwithIFNBorglatirameracetate,afterreceivingthattherapyfor≥6months[priortreatmentwithothertherapieswasalsopermitted])

• Patientswererandomized2:1toreceivealemtuzumab12mg/dayviaintravenous(IV)infusions on 5 consecutive days at baseline and on 3 consecutive days 12 months later, or SCIFNB-1a44µg3timesweekly

Extension Study9

• Patients who had received alemtuzumab in the core study received re-treatment as neededintheextension(12mg/dayIVon3consecutivedays) – Re-treatmentcriteriawereoneofthefollowing,basedontheinvestigator’sclinical

decision: ■ ≥1protocol-definedrelapse ■ ≥2neworenlargingT2and/orgadolinium-enhancingbrainorspinallesionsonmagneticresonanceimaging

– Useofotherdisease-modifyingtherapies(DMTs)wasallowedbasedoninvestigators’clinical decisions

– AlldatapresentedherearefrompatientswhoreceivedalemtuzumabinthecoreCARE-MS II study

Disability Assessment• EDSSwasassessedbyblindedratersatcorestudybaselineandevery3months• Disabilityoutcomes

– ChangefromcorestudybaselineonEDSS – Proportionofpatientsimproved,remainedstable,orworsenedonEDSS

■ Improvementandworseningweredefinedas≥0.5-pointdecreaseorincrease,respectively,fromcorestudybaselineEDSSscore

– Sustained reduction in disability: decrease from core study baseline by ≥1EDSSpointconfirmedover3,6,or12monthsforpatientswithbaselineEDSSscores≥2.0

Statistical Analysis• AnalyseswerebasedonYear3follow-updataonpatientswhohadreceivedalemtuzumab12mginthecoreCARE-MSIIstudy

• DatafromCARE-MSIIpatientswhotransitionedintotheextensionstudywereanalyzedfromthetimeoffirsttreatment

• Kaplan-Meieranalysisoftimeto3-,6-,and12-monthsustainedreductionindisability• Analyseswereundertakenforallpatientsintheextensionandforpatientswhoreceived

only 2 courses over 3 years

RESULTSPatients• Morethan90%(393of423)ofpatientswhohadreceivedalemtuzumab12mginCARE-MSIIandcompletedthecorestudyenteredtheextension

• Approximately80%didnotreceivere-treatmentduringYear3• Fewerthan3%offormeralemtuzumab-treatedpatientsreceivedanotherDMTinYear3Disability Improvement • MeanEDSSscoreswere2.7atcorestudybaseline,2.5atYear2,and2.6atYear3(Figure 1)

• MeanEDSSscoresremainedbelowpre-treatmentvaluesduringthethirdyear – Year2meanEDSSscorechangefromcorestudybaseline:−0.21 – Year3meanEDSSscorechangefromcorestudybaseline:−0.06

• AtYear3,70%ofalemtuzumab-treatedpatientshadeitherstableorimprovedEDSSscores from core study baseline (Figure 2),similartotheresultsseenoverYears0–2

Acknowledgments and DisclosuresCARE-MSIIsteeringcommittee:DouglasLArnold,JeffreyACohen,AlasdairJColes,DAlastairSCompston,ChristianConfavreux*,EdwardFox,Hans-PeterHartung,EvaHavrdova,TamaraMiller,KrzysztofWSelmaj,CaryLTwyman,andHowardWeiner.Genzyme:AjiNair;LindaKasten.CARE-MSIIwassponsoredbyGenzyme,aSanoficompany,andBayerHealthcarePharmaceuticals.EditorialsupportforthisposterwasprovidedbyRichardHogan,EvidenceScientificSolutions,andwasfundedbyGenzyme.G.G.reportsreceivingcompensationforconsulting,servingonascientificadvisoryboard,speaking,orotheractivitiesfromBiogen-Idec,FivePrimeTherapeutics,Genzyme,GWPharma,Merck-Serono,Novartis,Roche,Synthon,Teva,andVertexPharmaceuticals.G.G.receivedcompensationforservingasajournaleditorforMultiple Sclerosis and Related DisordersandresearchsupportfromSerono.D.H.MandJ.P.reportreceivingpersonalcompensationasemployeesofGenzyme.J.H.reportsreceivingpersonalcompensationforconsulting,servingonascientificadvisoryboard,speaking,orotheractivitiesfromBiogenIdec.AlemtuzumabisapprovedinAustralia,theEuropeanUnion,andMexicofortreatmentofactiveRRMSdefinedbyclinicalorimagingfeatures,inBrazilfortreatmentofrelapsingformsofMS,andinCanadaforpatientswithinadequateresponsetointerferonbetaorotherDMTs.Rebif®isaregisteredtrademarkofEMDSerono,Inc.*Deceased.

Sustained Improvement in Disability Outcomes with Alemtuzumab in Active Relapsing-Remitting Multiple Sclerosis Patients Who Participated in CARE-MS II: Three-Year Follow-up

G Giovannoni,1DHMargolin,2 J Palmer,2 J Herbert3

1QueenMaryUniversityofLondon,BartsandTheLondonSchoolofMedicine,London,UK;2Genzyme,aSanoficompany,Cambridge,MA,USA;3NewYorkUniversityMedicalCenter,NewYork,NY,USA

Presented at the 66th Annual Meeting of the American Academy of Neurology (AAN), April 26–May 03, 2014, Philadelphia, PA

P3.165

Figure 2. Mean EDSS Change: Proportion Improved, Remained Stable, or Worsened in Patients Who Had Received Alemtuzumab 12 mg in the Core Study

• AtYear3,66%ofalemtuzumab-treatedpatientshadeitherstableorimprovedEDSSscores from extension study baseline (data not shown)

• AmongpatientswhoseEDSSscoreremainedstablefrombaselinetoYear2,75%eithercontinuedtoremainstableorexperiencedimprovementfromYears2–3(Figure 3)

• AmongpatientswhoseEDSSscoreimprovedfrombaselinetoYear2,58%remainedstableorimprovedfurtherfromYears2–3(Figure 3)

Sustained Reduction in Preexisting Disability• AtYear3,morethanonethirdofpatientswhohadreceivedalemtuzumab12mginthecorestudyattainedimprovementinpreexistingdisabilitysustainedfor6months,asmeasured by 6-month sustained reduction in disability (Figure 4) – Aboutonequarterofthepatientsachieved12-monthsustainedreductionindisability

at Year 3

Durability of Effect • MeanEDSSscoreatYear3was2.5forpatientswhoreceived2coursesofalemtuzumab

over 3 years – Year3meanEDSSscorechangefromcorestudybaselinewas−0.16inthispatientsubgroup

• AtYear3,EDSSscorewasimprovedfromcorestudybaselinein48%ofpatientswhoreceived2coursesofalemtuzumabover3yearsandstableinafurther28%ofpatients(data not shown)

• AmongpatientswhoseEDSSscoreremainedstablefrombaselinetoYear2,79%eithercontinuedtoremainstableorexperiencedimprovementfromYears2–3(Figure 5)

• AmongpatientswhoseEDSSscoreimprovedfrombaselinetoYear2,61%remainedstableorimprovedfurtherfromYears2–3(Figure 5)

Sustained Reduction in Preexisting Disability• Forpatientswhoreceivedonly2coursesofalemtuzumabover3years,theproportionsachieving3-,6-,and12-monthsustainedreductionindisabilitywere45%,37%,and28% at Year 3 (data not shown)

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;EDSS=ExpandedDisabilityStatusScale.

EDSS=ExpandedDisabilityStatusScale

Figure 1. EDSS Score over Time in the Core Study and Extension

0 6 12 18 24 30 363 9 15 21 27 33

426 419 422 410 416 373 370419 419 415 413 367 364

0

2.00

2.40

2.60

2.20

2.80Baseline EDSS

3.00

Follow-up MonthNo. of Patients

EDSS

Sco

re

Alemtuzumab 12 mg

CARE-MS II Core Study Extension

(N=423)Years 0–2

(N=369)Years 0–3

Prop

ortio

n of

Pat

ient

s (%

)

60 Improved

Remained stable

Worsened50

40

30

20

10

0

46

302524

30

45

(N=178)

ImprovedYears 0–2

EDSS Shift Category (Baseline through Year 2)(N=112)

Remained stableYears 0–2

Prop

ortio

n of

Pat

ient

sat

Yea

r 3 (%

) 60

70

80 Improved from Year 2 to Year 3

Remained Stable from Year 2 to Year 3

50

40

30

20

10

011.8

46.651.8

23.2

Figure 3. EDSS Improvement from Year 2 to Year 3 in Alemtuzumab-treated Patients Who Improved or Remained Stable from Baseline to Year 2

EDSS=ExpandedDisabilityStatusScale

35%

43%

0 6 12 18 24 30 360

10

20

30

40

50

Follow-up Month

CARE-MS II Core Study Extension

321 280 241 222 200 172 1623-Month SRD

Prop

ortio

n of

Pat

ient

s w

ith S

usta

ined

R

educ

tion

in D

isab

ility

(%)

29%35%

321 290 262 245 221 190 1826-Month SRD

22%27%

321 294 275 263 245 215 20712-Month SRD

No. at Risk

Figure 4. Percentage of Patients with 3-, 6-, and 12-Month Sustained Reduction in Disability

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;SRD=sustainedreductionindisability

Figure 5. EDSS Improvement from Year 2 to Year 3 in Patients Treated with 2 Courses of Alemtuzumab over 3 Years Who Improved or Remained Stable from Baseline to Year 2

EDSS=ExpandedDisabilityStatusScale

(N=148)

ImprovedYears 0–2

EDSS Shift Category (Baseline through Year 2)(N=96)

Remained stableYears 0–2

Prop

ortio

n of

Pat

ient

sat

Yea

r 3 (%

) 60

70

80 Improved from Year 2 to Year 3

Remained Stable from Year 2 to Year 3

50

40

30

20

10

012.2

48.654.2

25.0

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;EDSS=ExpandedDisabilityStatusScale

REFERENCES1. Hu Y, et al. Immunology 2009;128:260-70. 2. Weber MS, Hemmer B. Results Probl Cell Differ 2010;51:115-26. 3. Havari E, et al. Immunology 2014;141:123-31. 4. Cox AL, et al. Eur J Immunol 2005;35:3332-42. 5. Coles AJ, et al. N Engl J Med 2008;359:1786-801. 6. Cohen JA, et al. Lancet 2012;380:1819-28. 7. Coles AJ, et al. Lancet 2012;380:1829-39. 8. Graves J, et al. Neurology 2013;30 (abstract P3.158). 9. Fox EJ, et al. Neurology 2013;30 (abstract S41.001).

CONCLUSIONS• Interim data from the CARE-MS II extension study demonstrate that alemtuzumabhasdurableefficacyondisabilitythrough3yearsinpatientswhohadrelapsedonpriortherapy,despitethemajorityofpatientsreceivingnoadditionalalemtuzumabtreatmentcoursesorotherDMTs – AlmosthalfofalemtuzumabpatientsdemonstratedimproveddisabilityscoresatYear3comparedwiththatatstudybaseline

– Morethanonethirdofformeralemtuzumabpatientsattainedsustaineddisabilityimprovement(6-monthsustainedreductionindisability) by Year 3

– Similardisabilityoutcomeswereobservedinpatientswhoreceivedonly 2 treatment courses over 3 years

• Thesefindings,togetherwithpreviouslyreporteddata,supportthepositivebenefit-riskprofileforalemtuzumabasapotentialtreatmentforRRMSinpatientswhorelapsedonpriortherapy

INTRODUCTION• AlemtuzumabisahumanizedmonoclonalantibodyapprovedinAustralia,Brazil,Canada,theEuropeanUnion,andMexicoforthetreatmentofactiverelapsing-remittingmultiplesclerosis(RRMS)thatselectivelytargetsCD52,resultingindepletionandsubsequentrepopulationofcirculatingTandBlymphocytes1-4

• Alemtuzumab,administeredin2annualcourses,hasdemonstratedsuperiorefficacyvs.high-dosesubcutaneousinterferonbeta-1a(SCIFNB-1a)intreatment-naiveRRMSpatients(CAMMS223[NCT00050778];ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis[CARE-MS]I[NCT00530348])5,6;andinpatientswhorelapsedonapriortherapy(CARE-MSII[NCT00548405])7 – Intheseclinicaltrials,alemtuzumabhadaconsistentandmanageablesafetyprofile,withthemostcommonadverseevents(AEs)beinginfusion-associatedreactions,non-serious infections, and autoimmune AEs

• InCARE-MSII,alemtuzumabsignificantlyreduced6-monthsustainedaccumulationofdisabilityat2yearsby49%beyondthatwithSCIFNB-1a(p<0.0001),andalemtuzumabpatientsweremorethantwiceaslikelytodemonstrate6-monthsustainedimprovementinpreexistingdisability(hazardratio2.57;p=0.0002)7 – PatientstreatedwithalemtuzumabalsohadsignificantlyimprovedvisualoutcomesusingSloanlow-contrastacuitymetrics,andfunctionaloutcomesusingMultipleSclerosisFunctionalComposite,comparedwithSCIFNB-1aatYear2(p<0.05)7,8

OBJECTIVE• ThepresentstudyexaminedthedurabilityofdisabilityimprovementinYear3follow-upduringanongoingextensionstudy(NCT00930553)ofalemtuzumabpatientswhorelapsedonapriortherapy

METHODSStudy DesignCore Study7

• CARE-MSIIwasarandomized,rater-blinded,active-controlled,head-to-head,phase3trial of 24 months’ duration

• Entrycriteriaincludedage18–55years,baselineExpandedDisabilityStatusScale(EDSS)score ≤5,MSsymptomonsetwithin10years,activeRRMS(≥2relapsesinprior2yearsand ≥1intheprioryear),andrelapseonpriortherapy(≥1relapseduringtreatmentwithIFNBorglatirameracetate,afterreceivingthattherapyfor≥6months[priortreatmentwithothertherapieswasalsopermitted])

• Patientswererandomized2:1toreceivealemtuzumab12mg/dayviaintravenous(IV)infusions on 5 consecutive days at baseline and on 3 consecutive days 12 months later, or SCIFNB-1a44µg3timesweekly

Extension Study9

• Patients who had received alemtuzumab in the core study received re-treatment as neededintheextension(12mg/dayIVon3consecutivedays) – Re-treatmentcriteriawereoneofthefollowing,basedontheinvestigator’sclinical

decision: ■ ≥1protocol-definedrelapse ■ ≥2neworenlargingT2and/orgadolinium-enhancingbrainorspinallesionsonmagneticresonanceimaging

– Useofotherdisease-modifyingtherapies(DMTs)wasallowedbasedoninvestigators’clinical decisions

– AlldatapresentedherearefrompatientswhoreceivedalemtuzumabinthecoreCARE-MS II study

Disability Assessment• EDSSwasassessedbyblindedratersatcorestudybaselineandevery3months• Disabilityoutcomes

– ChangefromcorestudybaselineonEDSS – Proportionofpatientsimproved,remainedstable,orworsenedonEDSS

■ Improvementandworseningweredefinedas≥0.5-pointdecreaseorincrease,respectively,fromcorestudybaselineEDSSscore

– Sustained reduction in disability: decrease from core study baseline by ≥1EDSSpointconfirmedover3,6,or12monthsforpatientswithbaselineEDSSscores≥2.0

Statistical Analysis• AnalyseswerebasedonYear3follow-updataonpatientswhohadreceivedalemtuzumab12mginthecoreCARE-MSIIstudy

• DatafromCARE-MSIIpatientswhotransitionedintotheextensionstudywereanalyzedfromthetimeoffirsttreatment

• Kaplan-Meieranalysisoftimeto3-,6-,and12-monthsustainedreductionindisability• Analyseswereundertakenforallpatientsintheextensionandforpatientswhoreceived

only 2 courses over 3 years

RESULTSPatients• Morethan90%(393of423)ofpatientswhohadreceivedalemtuzumab12mginCARE-MSIIandcompletedthecorestudyenteredtheextension

• Approximately80%didnotreceivere-treatmentduringYear3• Fewerthan3%offormeralemtuzumab-treatedpatientsreceivedanotherDMTinYear3Disability Improvement • MeanEDSSscoreswere2.7atcorestudybaseline,2.5atYear2,and2.6atYear3(Figure 1)

• MeanEDSSscoresremainedbelowpre-treatmentvaluesduringthethirdyear – Year2meanEDSSscorechangefromcorestudybaseline:−0.21 – Year3meanEDSSscorechangefromcorestudybaseline:−0.06

• AtYear3,70%ofalemtuzumab-treatedpatientshadeitherstableorimprovedEDSSscores from core study baseline (Figure 2),similartotheresultsseenoverYears0–2

Acknowledgments and DisclosuresCARE-MSIIsteeringcommittee:DouglasLArnold,JeffreyACohen,AlasdairJColes,DAlastairSCompston,ChristianConfavreux*,EdwardFox,Hans-PeterHartung,EvaHavrdova,TamaraMiller,KrzysztofWSelmaj,CaryLTwyman,andHowardWeiner.Genzyme:AjiNair;LindaKasten.CARE-MSIIwassponsoredbyGenzyme,aSanoficompany,andBayerHealthcarePharmaceuticals.EditorialsupportforthisposterwasprovidedbyRichardHogan,EvidenceScientificSolutions,andwasfundedbyGenzyme.G.G.reportsreceivingcompensationforconsulting,servingonascientificadvisoryboard,speaking,orotheractivitiesfromBiogen-Idec,FivePrimeTherapeutics,Genzyme,GWPharma,Merck-Serono,Novartis,Roche,Synthon,Teva,andVertexPharmaceuticals.G.G.receivedcompensationforservingasajournaleditorforMultiple Sclerosis and Related DisordersandresearchsupportfromSerono.D.H.MandJ.P.reportreceivingpersonalcompensationasemployeesofGenzyme.J.H.reportsreceivingpersonalcompensationforconsulting,servingonascientificadvisoryboard,speaking,orotheractivitiesfromBiogenIdec.AlemtuzumabisapprovedinAustralia,theEuropeanUnion,andMexicofortreatmentofactiveRRMSdefinedbyclinicalorimagingfeatures,inBrazilfortreatmentofrelapsingformsofMS,andinCanadaforpatientswithinadequateresponsetointerferonbetaorotherDMTs.Rebif®isaregisteredtrademarkofEMDSerono,Inc.*Deceased.

Sustained Improvement in Disability Outcomes with Alemtuzumab in Active Relapsing-Remitting Multiple Sclerosis Patients Who Participated in CARE-MS II: Three-Year Follow-up

G Giovannoni,1DHMargolin,2 J Palmer,2 J Herbert3

1QueenMaryUniversityofLondon,BartsandTheLondonSchoolofMedicine,London,UK;2Genzyme,aSanoficompany,Cambridge,MA,USA;3NewYorkUniversityMedicalCenter,NewYork,NY,USA

Presented at the 66th Annual Meeting of the American Academy of Neurology (AAN), April 26–May 03, 2014, Philadelphia, PA

P3.165

Figure 2. Mean EDSS Change: Proportion Improved, Remained Stable, or Worsened in Patients Who Had Received Alemtuzumab 12 mg in the Core Study

• AtYear3,66%ofalemtuzumab-treatedpatientshadeitherstableorimprovedEDSSscores from extension study baseline (data not shown)

• AmongpatientswhoseEDSSscoreremainedstablefrombaselinetoYear2,75%eithercontinuedtoremainstableorexperiencedimprovementfromYears2–3(Figure 3)

• AmongpatientswhoseEDSSscoreimprovedfrombaselinetoYear2,58%remainedstableorimprovedfurtherfromYears2–3(Figure 3)

Sustained Reduction in Preexisting Disability• AtYear3,morethanonethirdofpatientswhohadreceivedalemtuzumab12mginthecorestudyattainedimprovementinpreexistingdisabilitysustainedfor6months,asmeasured by 6-month sustained reduction in disability (Figure 4) – Aboutonequarterofthepatientsachieved12-monthsustainedreductionindisability

at Year 3

Durability of Effect • MeanEDSSscoreatYear3was2.5forpatientswhoreceived2coursesofalemtuzumab

over 3 years – Year3meanEDSSscorechangefromcorestudybaselinewas−0.16inthispatientsubgroup

• AtYear3,EDSSscorewasimprovedfromcorestudybaselinein48%ofpatientswhoreceived2coursesofalemtuzumabover3yearsandstableinafurther28%ofpatients(data not shown)

• AmongpatientswhoseEDSSscoreremainedstablefrombaselinetoYear2,79%eithercontinuedtoremainstableorexperiencedimprovementfromYears2–3(Figure 5)

• AmongpatientswhoseEDSSscoreimprovedfrombaselinetoYear2,61%remainedstableorimprovedfurtherfromYears2–3(Figure 5)

Sustained Reduction in Preexisting Disability• Forpatientswhoreceivedonly2coursesofalemtuzumabover3years,theproportionsachieving3-,6-,and12-monthsustainedreductionindisabilitywere45%,37%,and28% at Year 3 (data not shown)

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;EDSS=ExpandedDisabilityStatusScale.

EDSS=ExpandedDisabilityStatusScale

Figure 1. EDSS Score over Time in the Core Study and Extension

0 6 12 18 24 30 363 9 15 21 27 33

426 419 422 410 416 373 370419 419 415 413 367 364

0

2.00

2.40

2.60

2.20

2.80Baseline EDSS

3.00

Follow-up MonthNo. of PatientsED

SS S

core

Alemtuzumab 12 mg

CARE-MS II Core Study Extension

(N=423)Years 0–2

(N=369)Years 0–3

Prop

ortio

n of

Pat

ient

s (%

)

60 Improved

Remained stable

Worsened50

40

30

20

10

0

46

302524

30

45

(N=178)

ImprovedYears 0–2

EDSS Shift Category (Baseline through Year 2)(N=112)

Remained stableYears 0–2

Prop

ortio

n of

Pat

ient

sat

Yea

r 3 (%

) 60

70

80 Improved from Year 2 to Year 3

Remained Stable from Year 2 to Year 3

50

40

30

20

10

011.8

46.651.8

23.2

Figure 3. EDSS Improvement from Year 2 to Year 3 in Alemtuzumab-treated Patients Who Improved or Remained Stable from Baseline to Year 2

EDSS=ExpandedDisabilityStatusScale

35%

43%

0 6 12 18 24 30 360

10

20

30

40

50

Follow-up Month

CARE-MS II Core Study Extension

321 280 241 222 200 172 1623-Month SRD

Prop

ortio

n of

Pat

ient

s w

ith S

usta

ined

R

educ

tion

in D

isab

ility

(%)

29%35%

321 290 262 245 221 190 1826-Month SRD

22%27%

321 294 275 263 245 215 20712-Month SRD

No. at Risk

Figure 4. Percentage of Patients with 3-, 6-, and 12-Month Sustained Reduction in Disability

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;SRD=sustainedreductionindisability

Figure 5. EDSS Improvement from Year 2 to Year 3 in Patients Treated with 2 Courses of Alemtuzumab over 3 Years Who Improved or Remained Stable from Baseline to Year 2

EDSS=ExpandedDisabilityStatusScale

(N=148)

ImprovedYears 0–2

EDSS Shift Category (Baseline through Year 2)(N=96)

Remained stableYears 0–2

Prop

ortio

n of

Pat

ient

sat

Yea

r 3 (%

) 60

70

80 Improved from Year 2 to Year 3

Remained Stable from Year 2 to Year 3

50

40

30

20

10

012.2

48.654.2

25.0

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;EDSS=ExpandedDisabilityStatusScale

REFERENCES1. Hu Y, et al. Immunology 2009;128:260-70. 2. Weber MS, Hemmer B. Results Probl Cell Differ 2010;51:115-26. 3. Havari E, et al. Immunology 2014;141:123-31. 4. Cox AL, et al. Eur J Immunol 2005;35:3332-42. 5. Coles AJ, et al. N Engl J Med 2008;359:1786-801. 6. Cohen JA, et al. Lancet 2012;380:1819-28. 7. Coles AJ, et al. Lancet 2012;380:1829-39. 8. Graves J, et al. Neurology 2013;30 (abstract P3.158). 9. Fox EJ, et al. Neurology 2013;30 (abstract S41.001).

CONCLUSIONS• Interim data from the CARE-MS II extension study demonstrate that alemtuzumabhasdurableefficacyondisabilitythrough3yearsinpatientswhohadrelapsedonpriortherapy,despitethemajorityofpatientsreceivingnoadditionalalemtuzumabtreatmentcoursesorotherDMTs – AlmosthalfofalemtuzumabpatientsdemonstratedimproveddisabilityscoresatYear3comparedwiththatatstudybaseline

– Morethanonethirdofformeralemtuzumabpatientsattainedsustaineddisabilityimprovement(6-monthsustainedreductionindisability) by Year 3

– Similardisabilityoutcomeswereobservedinpatientswhoreceivedonly 2 treatment courses over 3 years

• Thesefindings,togetherwithpreviouslyreporteddata,supportthepositivebenefit-riskprofileforalemtuzumabasapotentialtreatmentforRRMSinpatientswhorelapsedonpriortherapy

INTRODUCTION• AlemtuzumabisahumanizedmonoclonalantibodyapprovedinAustralia,Brazil,Canada,theEuropeanUnion,andMexicoforthetreatmentofactiverelapsing-remittingmultiplesclerosis(RRMS)thatselectivelytargetsCD52,resultingindepletionandsubsequentrepopulationofcirculatingTandBlymphocytes1-4

• Alemtuzumab,administeredin2annualcourses,hasdemonstratedsuperiorefficacyvs.high-dosesubcutaneousinterferonbeta-1a(SCIFNB-1a)intreatment-naiveRRMSpatients(CAMMS223[NCT00050778];ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis[CARE-MS]I[NCT00530348])5,6;andinpatientswhorelapsedonapriortherapy(CARE-MSII[NCT00548405])7 – Intheseclinicaltrials,alemtuzumabhadaconsistentandmanageablesafetyprofile,withthemostcommonadverseevents(AEs)beinginfusion-associatedreactions,non-serious infections, and autoimmune AEs

• InCARE-MSII,alemtuzumabsignificantlyreduced6-monthsustainedaccumulationofdisabilityat2yearsby49%beyondthatwithSCIFNB-1a(p<0.0001),andalemtuzumabpatientsweremorethantwiceaslikelytodemonstrate6-monthsustainedimprovementinpreexistingdisability(hazardratio2.57;p=0.0002)7 – PatientstreatedwithalemtuzumabalsohadsignificantlyimprovedvisualoutcomesusingSloanlow-contrastacuitymetrics,andfunctionaloutcomesusingMultipleSclerosisFunctionalComposite,comparedwithSCIFNB-1aatYear2(p<0.05)7,8

OBJECTIVE• ThepresentstudyexaminedthedurabilityofdisabilityimprovementinYear3follow-upduringanongoingextensionstudy(NCT00930553)ofalemtuzumabpatientswhorelapsedonapriortherapy

METHODSStudy DesignCore Study7

• CARE-MSIIwasarandomized,rater-blinded,active-controlled,head-to-head,phase3trial of 24 months’ duration

• Entrycriteriaincludedage18–55years,baselineExpandedDisabilityStatusScale(EDSS)score ≤5,MSsymptomonsetwithin10years,activeRRMS(≥2relapsesinprior2yearsand ≥1intheprioryear),andrelapseonpriortherapy(≥1relapseduringtreatmentwithIFNBorglatirameracetate,afterreceivingthattherapyfor≥6months[priortreatmentwithothertherapieswasalsopermitted])

• Patientswererandomized2:1toreceivealemtuzumab12mg/dayviaintravenous(IV)infusions on 5 consecutive days at baseline and on 3 consecutive days 12 months later, or SCIFNB-1a44µg3timesweekly

Extension Study9

• Patients who had received alemtuzumab in the core study received re-treatment as neededintheextension(12mg/dayIVon3consecutivedays) – Re-treatmentcriteriawereoneofthefollowing,basedontheinvestigator’sclinical

decision: ■ ≥1protocol-definedrelapse ■ ≥2neworenlargingT2and/orgadolinium-enhancingbrainorspinallesionsonmagneticresonanceimaging

– Useofotherdisease-modifyingtherapies(DMTs)wasallowedbasedoninvestigators’clinical decisions

– AlldatapresentedherearefrompatientswhoreceivedalemtuzumabinthecoreCARE-MS II study

Disability Assessment• EDSSwasassessedbyblindedratersatcorestudybaselineandevery3months• Disabilityoutcomes

– ChangefromcorestudybaselineonEDSS – Proportionofpatientsimproved,remainedstable,orworsenedonEDSS

■ Improvementandworseningweredefinedas≥0.5-pointdecreaseorincrease,respectively,fromcorestudybaselineEDSSscore

– Sustained reduction in disability: decrease from core study baseline by ≥1EDSSpointconfirmedover3,6,or12monthsforpatientswithbaselineEDSSscores≥2.0

Statistical Analysis• AnalyseswerebasedonYear3follow-updataonpatientswhohadreceivedalemtuzumab12mginthecoreCARE-MSIIstudy

• DatafromCARE-MSIIpatientswhotransitionedintotheextensionstudywereanalyzedfromthetimeoffirsttreatment

• Kaplan-Meieranalysisoftimeto3-,6-,and12-monthsustainedreductionindisability• Analyseswereundertakenforallpatientsintheextensionandforpatientswhoreceived

only 2 courses over 3 years

RESULTSPatients• Morethan90%(393of423)ofpatientswhohadreceivedalemtuzumab12mginCARE-MSIIandcompletedthecorestudyenteredtheextension

• Approximately80%didnotreceivere-treatmentduringYear3• Fewerthan3%offormeralemtuzumab-treatedpatientsreceivedanotherDMTinYear3Disability Improvement • MeanEDSSscoreswere2.7atcorestudybaseline,2.5atYear2,and2.6atYear3(Figure 1)

• MeanEDSSscoresremainedbelowpre-treatmentvaluesduringthethirdyear – Year2meanEDSSscorechangefromcorestudybaseline:−0.21 – Year3meanEDSSscorechangefromcorestudybaseline:−0.06

• AtYear3,70%ofalemtuzumab-treatedpatientshadeitherstableorimprovedEDSSscores from core study baseline (Figure 2),similartotheresultsseenoverYears0–2

Acknowledgments and DisclosuresCARE-MSIIsteeringcommittee:DouglasLArnold,JeffreyACohen,AlasdairJColes,DAlastairSCompston,ChristianConfavreux*,EdwardFox,Hans-PeterHartung,EvaHavrdova,TamaraMiller,KrzysztofWSelmaj,CaryLTwyman,andHowardWeiner.Genzyme:AjiNair;LindaKasten.CARE-MSIIwassponsoredbyGenzyme,aSanoficompany,andBayerHealthcarePharmaceuticals.EditorialsupportforthisposterwasprovidedbyRichardHogan,EvidenceScientificSolutions,andwasfundedbyGenzyme.G.G.reportsreceivingcompensationforconsulting,servingonascientificadvisoryboard,speaking,orotheractivitiesfromBiogen-Idec,FivePrimeTherapeutics,Genzyme,GWPharma,Merck-Serono,Novartis,Roche,Synthon,Teva,andVertexPharmaceuticals.G.G.receivedcompensationforservingasajournaleditorforMultiple Sclerosis and Related DisordersandresearchsupportfromSerono.D.H.MandJ.P.reportreceivingpersonalcompensationasemployeesofGenzyme.J.H.reportsreceivingpersonalcompensationforconsulting,servingonascientificadvisoryboard,speaking,orotheractivitiesfromBiogenIdec.AlemtuzumabisapprovedinAustralia,theEuropeanUnion,andMexicofortreatmentofactiveRRMSdefinedbyclinicalorimagingfeatures,inBrazilfortreatmentofrelapsingformsofMS,andinCanadaforpatientswithinadequateresponsetointerferonbetaorotherDMTs.Rebif®isaregisteredtrademarkofEMDSerono,Inc.*Deceased.

Sustained Improvement in Disability Outcomes with Alemtuzumab in Active Relapsing-Remitting Multiple Sclerosis Patients Who Participated in CARE-MS II: Three-Year Follow-up

G Giovannoni,1DHMargolin,2 J Palmer,2 J Herbert3

1QueenMaryUniversityofLondon,BartsandTheLondonSchoolofMedicine,London,UK;2Genzyme,aSanoficompany,Cambridge,MA,USA;3NewYorkUniversityMedicalCenter,NewYork,NY,USA

Presented at the 66th Annual Meeting of the American Academy of Neurology (AAN), April 26–May 03, 2014, Philadelphia, PA

P3.165

Figure 2. Mean EDSS Change: Proportion Improved, Remained Stable, or Worsened in Patients Who Had Received Alemtuzumab 12 mg in the Core Study

• AtYear3,66%ofalemtuzumab-treatedpatientshadeitherstableorimprovedEDSSscores from extension study baseline (data not shown)

• AmongpatientswhoseEDSSscoreremainedstablefrombaselinetoYear2,75%eithercontinuedtoremainstableorexperiencedimprovementfromYears2–3(Figure 3)

• AmongpatientswhoseEDSSscoreimprovedfrombaselinetoYear2,58%remainedstableorimprovedfurtherfromYears2–3(Figure 3)

Sustained Reduction in Preexisting Disability• AtYear3,morethanonethirdofpatientswhohadreceivedalemtuzumab12mginthecorestudyattainedimprovementinpreexistingdisabilitysustainedfor6months,asmeasured by 6-month sustained reduction in disability (Figure 4) – Aboutonequarterofthepatientsachieved12-monthsustainedreductionindisability

at Year 3

Durability of Effect • MeanEDSSscoreatYear3was2.5forpatientswhoreceived2coursesofalemtuzumab

over 3 years – Year3meanEDSSscorechangefromcorestudybaselinewas−0.16inthispatientsubgroup

• AtYear3,EDSSscorewasimprovedfromcorestudybaselinein48%ofpatientswhoreceived2coursesofalemtuzumabover3yearsandstableinafurther28%ofpatients(data not shown)

• AmongpatientswhoseEDSSscoreremainedstablefrombaselinetoYear2,79%eithercontinuedtoremainstableorexperiencedimprovementfromYears2–3(Figure 5)

• AmongpatientswhoseEDSSscoreimprovedfrombaselinetoYear2,61%remainedstableorimprovedfurtherfromYears2–3(Figure 5)

Sustained Reduction in Preexisting Disability• Forpatientswhoreceivedonly2coursesofalemtuzumabover3years,theproportionsachieving3-,6-,and12-monthsustainedreductionindisabilitywere45%,37%,and28% at Year 3 (data not shown)

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;EDSS=ExpandedDisabilityStatusScale.

EDSS=ExpandedDisabilityStatusScale

Figure 1. EDSS Score over Time in the Core Study and Extension

0 6 12 18 24 30 363 9 15 21 27 33

426 419 422 410 416 373 370419 419 415 413 367 364

0

2.00

2.40

2.60

2.20

2.80Baseline EDSS

3.00

Follow-up MonthNo. of Patients

EDSS

Sco

re

Alemtuzumab 12 mg

CARE-MS II Core Study Extension

(N=423)Years 0–2

(N=369)Years 0–3

Prop

ortio

n of

Pat

ient

s (%

)

60 Improved

Remained stable

Worsened50

40

30

20

10

0

46

302524

30

45

(N=178)

ImprovedYears 0–2

EDSS Shift Category (Baseline through Year 2)(N=112)

Remained stableYears 0–2

Prop

ortio

n of

Pat

ient

sat

Yea

r 3 (%

) 60

70

80 Improved from Year 2 to Year 3

Remained Stable from Year 2 to Year 3

50

40

30

20

10

011.8

46.651.8

23.2

Figure 3. EDSS Improvement from Year 2 to Year 3 in Alemtuzumab-treated Patients Who Improved or Remained Stable from Baseline to Year 2

EDSS=ExpandedDisabilityStatusScale

35%

43%

0 6 12 18 24 30 360

10

20

30

40

50

Follow-up Month

CARE-MS II Core Study Extension

321 280 241 222 200 172 1623-Month SRD

Prop

ortio

n of

Pat

ient

s w

ith S

usta

ined

R

educ

tion

in D

isab

ility

(%)

29%35%

321 290 262 245 221 190 1826-Month SRD

22%27%

321 294 275 263 245 215 20712-Month SRD

No. at Risk

Figure 4. Percentage of Patients with 3-, 6-, and 12-Month Sustained Reduction in Disability

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;SRD=sustainedreductionindisability

Figure 5. EDSS Improvement from Year 2 to Year 3 in Patients Treated with 2 Courses of Alemtuzumab over 3 Years Who Improved or Remained Stable from Baseline to Year 2

EDSS=ExpandedDisabilityStatusScale

(N=148)

ImprovedYears 0–2

EDSS Shift Category (Baseline through Year 2)(N=96)

Remained stableYears 0–2

Prop

ortio

n of

Pat

ient

sat

Yea

r 3 (%

) 60

70

80 Improved from Year 2 to Year 3

Remained Stable from Year 2 to Year 3

50

40

30

20

10

012.2

48.654.2

25.0

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;EDSS=ExpandedDisabilityStatusScale

REFERENCES1. Hu Y, et al. Immunology 2009;128:260-70. 2. Weber MS, Hemmer B. Results Probl Cell Differ 2010;51:115-26. 3. Havari E, et al. Immunology 2014;141:123-31. 4. Cox AL, et al. Eur J Immunol 2005;35:3332-42. 5. Coles AJ, et al. N Engl J Med 2008;359:1786-801. 6. Cohen JA, et al. Lancet 2012;380:1819-28. 7. Coles AJ, et al. Lancet 2012;380:1829-39. 8. Graves J, et al. Neurology 2013;30 (abstract P3.158). 9. Fox EJ, et al. Neurology 2013;30 (abstract S41.001).

CONCLUSIONS• Interim data from the CARE-MS II extension study demonstrate that alemtuzumabhasdurableefficacyondisabilitythrough3yearsinpatientswhohadrelapsedonpriortherapy,despitethemajorityofpatientsreceivingnoadditionalalemtuzumabtreatmentcoursesorotherDMTs – AlmosthalfofalemtuzumabpatientsdemonstratedimproveddisabilityscoresatYear3comparedwiththatatstudybaseline

– Morethanonethirdofformeralemtuzumabpatientsattainedsustaineddisabilityimprovement(6-monthsustainedreductionindisability) by Year 3

– Similardisabilityoutcomeswereobservedinpatientswhoreceivedonly 2 treatment courses over 3 years

• Thesefindings,togetherwithpreviouslyreporteddata,supportthepositivebenefit-riskprofileforalemtuzumabasapotentialtreatmentforRRMSinpatientswhorelapsedonpriortherapy

INTRODUCTION• AlemtuzumabisahumanizedmonoclonalantibodyapprovedinAustralia,Brazil,Canada,theEuropeanUnion,andMexicoforthetreatmentofactiverelapsing-remittingmultiplesclerosis(RRMS)thatselectivelytargetsCD52,resultingindepletionandsubsequentrepopulationofcirculatingTandBlymphocytes1-4

• Alemtuzumab,administeredin2annualcourses,hasdemonstratedsuperiorefficacyvs.high-dosesubcutaneousinterferonbeta-1a(SCIFNB-1a)intreatment-naiveRRMSpatients(CAMMS223[NCT00050778];ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis[CARE-MS]I[NCT00530348])5,6;andinpatientswhorelapsedonapriortherapy(CARE-MSII[NCT00548405])7 – Intheseclinicaltrials,alemtuzumabhadaconsistentandmanageablesafetyprofile,withthemostcommonadverseevents(AEs)beinginfusion-associatedreactions,non-serious infections, and autoimmune AEs

• InCARE-MSII,alemtuzumabsignificantlyreduced6-monthsustainedaccumulationofdisabilityat2yearsby49%beyondthatwithSCIFNB-1a(p<0.0001),andalemtuzumabpatientsweremorethantwiceaslikelytodemonstrate6-monthsustainedimprovementinpreexistingdisability(hazardratio2.57;p=0.0002)7 – PatientstreatedwithalemtuzumabalsohadsignificantlyimprovedvisualoutcomesusingSloanlow-contrastacuitymetrics,andfunctionaloutcomesusingMultipleSclerosisFunctionalComposite,comparedwithSCIFNB-1aatYear2(p<0.05)7,8

OBJECTIVE• ThepresentstudyexaminedthedurabilityofdisabilityimprovementinYear3follow-upduringanongoingextensionstudy(NCT00930553)ofalemtuzumabpatientswhorelapsedonapriortherapy

METHODSStudy DesignCore Study7

• CARE-MSIIwasarandomized,rater-blinded,active-controlled,head-to-head,phase3trial of 24 months’ duration

• Entrycriteriaincludedage18–55years,baselineExpandedDisabilityStatusScale(EDSS)score ≤5,MSsymptomonsetwithin10years,activeRRMS(≥2relapsesinprior2yearsand ≥1intheprioryear),andrelapseonpriortherapy(≥1relapseduringtreatmentwithIFNBorglatirameracetate,afterreceivingthattherapyfor≥6months[priortreatmentwithothertherapieswasalsopermitted])

• Patientswererandomized2:1toreceivealemtuzumab12mg/dayviaintravenous(IV)infusions on 5 consecutive days at baseline and on 3 consecutive days 12 months later, or SCIFNB-1a44µg3timesweekly

Extension Study9

• Patients who had received alemtuzumab in the core study received re-treatment as neededintheextension(12mg/dayIVon3consecutivedays) – Re-treatmentcriteriawereoneofthefollowing,basedontheinvestigator’sclinical

decision: ■ ≥1protocol-definedrelapse ■ ≥2neworenlargingT2and/orgadolinium-enhancingbrainorspinallesionsonmagneticresonanceimaging

– Useofotherdisease-modifyingtherapies(DMTs)wasallowedbasedoninvestigators’clinical decisions

– AlldatapresentedherearefrompatientswhoreceivedalemtuzumabinthecoreCARE-MS II study

Disability Assessment• EDSSwasassessedbyblindedratersatcorestudybaselineandevery3months• Disabilityoutcomes

– ChangefromcorestudybaselineonEDSS – Proportionofpatientsimproved,remainedstable,orworsenedonEDSS

■ Improvementandworseningweredefinedas≥0.5-pointdecreaseorincrease,respectively,fromcorestudybaselineEDSSscore

– Sustained reduction in disability: decrease from core study baseline by ≥1EDSSpointconfirmedover3,6,or12monthsforpatientswithbaselineEDSSscores≥2.0

Statistical Analysis• AnalyseswerebasedonYear3follow-updataonpatientswhohadreceivedalemtuzumab12mginthecoreCARE-MSIIstudy

• DatafromCARE-MSIIpatientswhotransitionedintotheextensionstudywereanalyzedfromthetimeoffirsttreatment

• Kaplan-Meieranalysisoftimeto3-,6-,and12-monthsustainedreductionindisability• Analyseswereundertakenforallpatientsintheextensionandforpatientswhoreceived

only 2 courses over 3 years

RESULTSPatients• Morethan90%(393of423)ofpatientswhohadreceivedalemtuzumab12mginCARE-MSIIandcompletedthecorestudyenteredtheextension

• Approximately80%didnotreceivere-treatmentduringYear3• Fewerthan3%offormeralemtuzumab-treatedpatientsreceivedanotherDMTinYear3Disability Improvement • MeanEDSSscoreswere2.7atcorestudybaseline,2.5atYear2,and2.6atYear3(Figure 1)

• MeanEDSSscoresremainedbelowpre-treatmentvaluesduringthethirdyear – Year2meanEDSSscorechangefromcorestudybaseline:−0.21 – Year3meanEDSSscorechangefromcorestudybaseline:−0.06

• AtYear3,70%ofalemtuzumab-treatedpatientshadeitherstableorimprovedEDSSscores from core study baseline (Figure 2),similartotheresultsseenoverYears0–2

Acknowledgments and DisclosuresCARE-MSIIsteeringcommittee:DouglasLArnold,JeffreyACohen,AlasdairJColes,DAlastairSCompston,ChristianConfavreux*,EdwardFox,Hans-PeterHartung,EvaHavrdova,TamaraMiller,KrzysztofWSelmaj,CaryLTwyman,andHowardWeiner.Genzyme:AjiNair;LindaKasten.CARE-MSIIwassponsoredbyGenzyme,aSanoficompany,andBayerHealthcarePharmaceuticals.EditorialsupportforthisposterwasprovidedbyRichardHogan,EvidenceScientificSolutions,andwasfundedbyGenzyme.G.G.reportsreceivingcompensationforconsulting,servingonascientificadvisoryboard,speaking,orotheractivitiesfromBiogen-Idec,FivePrimeTherapeutics,Genzyme,GWPharma,Merck-Serono,Novartis,Roche,Synthon,Teva,andVertexPharmaceuticals.G.G.receivedcompensationforservingasajournaleditorforMultiple Sclerosis and Related DisordersandresearchsupportfromSerono.D.H.MandJ.P.reportreceivingpersonalcompensationasemployeesofGenzyme.J.H.reportsreceivingpersonalcompensationforconsulting,servingonascientificadvisoryboard,speaking,orotheractivitiesfromBiogenIdec.AlemtuzumabisapprovedinAustralia,theEuropeanUnion,andMexicofortreatmentofactiveRRMSdefinedbyclinicalorimagingfeatures,inBrazilfortreatmentofrelapsingformsofMS,andinCanadaforpatientswithinadequateresponsetointerferonbetaorotherDMTs.Rebif®isaregisteredtrademarkofEMDSerono,Inc.*Deceased.

Sustained Improvement in Disability Outcomes with Alemtuzumab in Active Relapsing-Remitting Multiple Sclerosis Patients Who Participated in CARE-MS II: Three-Year Follow-up

G Giovannoni,1DHMargolin,2 J Palmer,2 J Herbert3

1QueenMaryUniversityofLondon,BartsandTheLondonSchoolofMedicine,London,UK;2Genzyme,aSanoficompany,Cambridge,MA,USA;3NewYorkUniversityMedicalCenter,NewYork,NY,USA

Presented at the 66th Annual Meeting of the American Academy of Neurology (AAN), April 26–May 03, 2014, Philadelphia, PA

P3.165

Figure 2. Mean EDSS Change: Proportion Improved, Remained Stable, or Worsened in Patients Who Had Received Alemtuzumab 12 mg in the Core Study

• AtYear3,66%ofalemtuzumab-treatedpatientshadeitherstableorimprovedEDSSscores from extension study baseline (data not shown)

• AmongpatientswhoseEDSSscoreremainedstablefrombaselinetoYear2,75%eithercontinuedtoremainstableorexperiencedimprovementfromYears2–3(Figure 3)

• AmongpatientswhoseEDSSscoreimprovedfrombaselinetoYear2,58%remainedstableorimprovedfurtherfromYears2–3(Figure 3)

Sustained Reduction in Preexisting Disability• AtYear3,morethanonethirdofpatientswhohadreceivedalemtuzumab12mginthecorestudyattainedimprovementinpreexistingdisabilitysustainedfor6months,asmeasured by 6-month sustained reduction in disability (Figure 4) – Aboutonequarterofthepatientsachieved12-monthsustainedreductionindisability

at Year 3

Durability of Effect • MeanEDSSscoreatYear3was2.5forpatientswhoreceived2coursesofalemtuzumab

over 3 years – Year3meanEDSSscorechangefromcorestudybaselinewas−0.16inthispatientsubgroup

• AtYear3,EDSSscorewasimprovedfromcorestudybaselinein48%ofpatientswhoreceived2coursesofalemtuzumabover3yearsandstableinafurther28%ofpatients(data not shown)

• AmongpatientswhoseEDSSscoreremainedstablefrombaselinetoYear2,79%eithercontinuedtoremainstableorexperiencedimprovementfromYears2–3(Figure 5)

• AmongpatientswhoseEDSSscoreimprovedfrombaselinetoYear2,61%remainedstableorimprovedfurtherfromYears2–3(Figure 5)

Sustained Reduction in Preexisting Disability• Forpatientswhoreceivedonly2coursesofalemtuzumabover3years,theproportionsachieving3-,6-,and12-monthsustainedreductionindisabilitywere45%,37%,and28% at Year 3 (data not shown)

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;EDSS=ExpandedDisabilityStatusScale.

EDSS=ExpandedDisabilityStatusScale

Figure 1. EDSS Score over Time in the Core Study and Extension

0 6 12 18 24 30 363 9 15 21 27 33

426 419 422 410 416 373 370419 419 415 413 367 364

0

2.00

2.40

2.60

2.20

2.80Baseline EDSS

3.00

Follow-up MonthNo. of Patients

EDSS

Sco

re

Alemtuzumab 12 mg

CARE-MS II Core Study Extension

(N=423)Years 0–2

(N=369)Years 0–3

Prop

ortio

n of

Pat

ient

s (%

)

60 Improved

Remained stable

Worsened50

40

30

20

10

0

46

302524

30

45

(N=178)

ImprovedYears 0–2

EDSS Shift Category (Baseline through Year 2)(N=112)

Remained stableYears 0–2

Prop

ortio

n of

Pat

ient

sat

Yea

r 3 (%

) 60

70

80 Improved from Year 2 to Year 3

Remained Stable from Year 2 to Year 3

50

40

30

20

10

011.8

46.651.8

23.2

Figure 3. EDSS Improvement from Year 2 to Year 3 in Alemtuzumab-treated Patients Who Improved or Remained Stable from Baseline to Year 2

EDSS=ExpandedDisabilityStatusScale

35%

43%

0 6 12 18 24 30 360

10

20

30

40

50

Follow-up Month

CARE-MS II Core Study Extension

321 280 241 222 200 172 1623-Month SRD

Prop

ortio

n of

Pat

ient

s w

ith S

usta

ined

R

educ

tion

in D

isab

ility

(%)

29%35%

321 290 262 245 221 190 1826-Month SRD

22%27%

321 294 275 263 245 215 20712-Month SRD

No. at Risk

Figure 4. Percentage of Patients with 3-, 6-, and 12-Month Sustained Reduction in Disability

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;SRD=sustainedreductionindisability

Figure 5. EDSS Improvement from Year 2 to Year 3 in Patients Treated with 2 Courses of Alemtuzumab over 3 Years Who Improved or Remained Stable from Baseline to Year 2

EDSS=ExpandedDisabilityStatusScale

(N=148)

ImprovedYears 0–2

EDSS Shift Category (Baseline through Year 2)(N=96)

Remained stableYears 0–2

Prop

ortio

n of

Pat

ient

sat

Yea

r 3 (%

) 60

70

80 Improved from Year 2 to Year 3

Remained Stable from Year 2 to Year 3

50

40

30

20

10

012.2

48.654.2

25.0

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;EDSS=ExpandedDisabilityStatusScale

REFERENCES1. Hu Y, et al. Immunology 2009;128:260-70. 2. Weber MS, Hemmer B. Results Probl Cell Differ 2010;51:115-26. 3. Havari E, et al. Immunology 2014;141:123-31. 4. Cox AL, et al. Eur J Immunol 2005;35:3332-42. 5. Coles AJ, et al. N Engl J Med 2008;359:1786-801. 6. Cohen JA, et al. Lancet 2012;380:1819-28. 7. Coles AJ, et al. Lancet 2012;380:1829-39. 8. Graves J, et al. Neurology 2013;30 (abstract P3.158). 9. Fox EJ, et al. Neurology 2013;30 (abstract S41.001).

CONCLUSIONS• Interim data from the CARE-MS II extension study demonstrate that alemtuzumabhasdurableefficacyondisabilitythrough3yearsinpatientswhohadrelapsedonpriortherapy,despitethemajorityofpatientsreceivingnoadditionalalemtuzumabtreatmentcoursesorotherDMTs – AlmosthalfofalemtuzumabpatientsdemonstratedimproveddisabilityscoresatYear3comparedwiththatatstudybaseline

– Morethanonethirdofformeralemtuzumabpatientsattainedsustaineddisabilityimprovement(6-monthsustainedreductionindisability) by Year 3

– Similardisabilityoutcomeswereobservedinpatientswhoreceivedonly 2 treatment courses over 3 years

• Thesefindings,togetherwithpreviouslyreporteddata,supportthepositivebenefit-riskprofileforalemtuzumabasapotentialtreatmentforRRMSinpatientswhorelapsedonpriortherapy

INTRODUCTION• AlemtuzumabisahumanizedmonoclonalantibodyapprovedinAustralia,Brazil,Canada,theEuropeanUnion,andMexicoforthetreatmentofactiverelapsing-remittingmultiplesclerosis(RRMS)thatselectivelytargetsCD52,resultingindepletionandsubsequentrepopulationofcirculatingTandBlymphocytes1-4

• Alemtuzumab,administeredin2annualcourses,hasdemonstratedsuperiorefficacyvs.high-dosesubcutaneousinterferonbeta-1a(SCIFNB-1a)intreatment-naiveRRMSpatients(CAMMS223[NCT00050778];ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis[CARE-MS]I[NCT00530348])5,6;andinpatientswhorelapsedonapriortherapy(CARE-MSII[NCT00548405])7 – Intheseclinicaltrials,alemtuzumabhadaconsistentandmanageablesafetyprofile,withthemostcommonadverseevents(AEs)beinginfusion-associatedreactions,non-serious infections, and autoimmune AEs

• InCARE-MSII,alemtuzumabsignificantlyreduced6-monthsustainedaccumulationofdisabilityat2yearsby49%beyondthatwithSCIFNB-1a(p<0.0001),andalemtuzumabpatientsweremorethantwiceaslikelytodemonstrate6-monthsustainedimprovementinpreexistingdisability(hazardratio2.57;p=0.0002)7 – PatientstreatedwithalemtuzumabalsohadsignificantlyimprovedvisualoutcomesusingSloanlow-contrastacuitymetrics,andfunctionaloutcomesusingMultipleSclerosisFunctionalComposite,comparedwithSCIFNB-1aatYear2(p<0.05)7,8

OBJECTIVE• ThepresentstudyexaminedthedurabilityofdisabilityimprovementinYear3follow-upduringanongoingextensionstudy(NCT00930553)ofalemtuzumabpatientswhorelapsedonapriortherapy

METHODSStudy DesignCore Study7

• CARE-MSIIwasarandomized,rater-blinded,active-controlled,head-to-head,phase3trial of 24 months’ duration

• Entrycriteriaincludedage18–55years,baselineExpandedDisabilityStatusScale(EDSS)score ≤5,MSsymptomonsetwithin10years,activeRRMS(≥2relapsesinprior2yearsand ≥1intheprioryear),andrelapseonpriortherapy(≥1relapseduringtreatmentwithIFNBorglatirameracetate,afterreceivingthattherapyfor≥6months[priortreatmentwithothertherapieswasalsopermitted])

• Patientswererandomized2:1toreceivealemtuzumab12mg/dayviaintravenous(IV)infusions on 5 consecutive days at baseline and on 3 consecutive days 12 months later, or SCIFNB-1a44µg3timesweekly

Extension Study9

• Patients who had received alemtuzumab in the core study received re-treatment as neededintheextension(12mg/dayIVon3consecutivedays) – Re-treatmentcriteriawereoneofthefollowing,basedontheinvestigator’sclinical

decision: ■ ≥1protocol-definedrelapse ■ ≥2neworenlargingT2and/orgadolinium-enhancingbrainorspinallesionsonmagneticresonanceimaging

– Useofotherdisease-modifyingtherapies(DMTs)wasallowedbasedoninvestigators’clinical decisions

– AlldatapresentedherearefrompatientswhoreceivedalemtuzumabinthecoreCARE-MS II study

Disability Assessment• EDSSwasassessedbyblindedratersatcorestudybaselineandevery3months• Disabilityoutcomes

– ChangefromcorestudybaselineonEDSS – Proportionofpatientsimproved,remainedstable,orworsenedonEDSS

■ Improvementandworseningweredefinedas≥0.5-pointdecreaseorincrease,respectively,fromcorestudybaselineEDSSscore

– Sustained reduction in disability: decrease from core study baseline by ≥1EDSSpointconfirmedover3,6,or12monthsforpatientswithbaselineEDSSscores≥2.0

Statistical Analysis• AnalyseswerebasedonYear3follow-updataonpatientswhohadreceivedalemtuzumab12mginthecoreCARE-MSIIstudy

• DatafromCARE-MSIIpatientswhotransitionedintotheextensionstudywereanalyzedfromthetimeoffirsttreatment

• Kaplan-Meieranalysisoftimeto3-,6-,and12-monthsustainedreductionindisability• Analyseswereundertakenforallpatientsintheextensionandforpatientswhoreceived

only 2 courses over 3 years

RESULTSPatients• Morethan90%(393of423)ofpatientswhohadreceivedalemtuzumab12mginCARE-MSIIandcompletedthecorestudyenteredtheextension

• Approximately80%didnotreceivere-treatmentduringYear3• Fewerthan3%offormeralemtuzumab-treatedpatientsreceivedanotherDMTinYear3Disability Improvement • MeanEDSSscoreswere2.7atcorestudybaseline,2.5atYear2,and2.6atYear3(Figure 1)

• MeanEDSSscoresremainedbelowpre-treatmentvaluesduringthethirdyear – Year2meanEDSSscorechangefromcorestudybaseline:−0.21 – Year3meanEDSSscorechangefromcorestudybaseline:−0.06

• AtYear3,70%ofalemtuzumab-treatedpatientshadeitherstableorimprovedEDSSscores from core study baseline (Figure 2),similartotheresultsseenoverYears0–2

Acknowledgments and DisclosuresCARE-MSIIsteeringcommittee:DouglasLArnold,JeffreyACohen,AlasdairJColes,DAlastairSCompston,ChristianConfavreux*,EdwardFox,Hans-PeterHartung,EvaHavrdova,TamaraMiller,KrzysztofWSelmaj,CaryLTwyman,andHowardWeiner.Genzyme:AjiNair;LindaKasten.CARE-MSIIwassponsoredbyGenzyme,aSanoficompany,andBayerHealthcarePharmaceuticals.EditorialsupportforthisposterwasprovidedbyRichardHogan,EvidenceScientificSolutions,andwasfundedbyGenzyme.G.G.reportsreceivingcompensationforconsulting,servingonascientificadvisoryboard,speaking,orotheractivitiesfromBiogen-Idec,FivePrimeTherapeutics,Genzyme,GWPharma,Merck-Serono,Novartis,Roche,Synthon,Teva,andVertexPharmaceuticals.G.G.receivedcompensationforservingasajournaleditorforMultiple Sclerosis and Related DisordersandresearchsupportfromSerono.D.H.MandJ.P.reportreceivingpersonalcompensationasemployeesofGenzyme.J.H.reportsreceivingpersonalcompensationforconsulting,servingonascientificadvisoryboard,speaking,orotheractivitiesfromBiogenIdec.AlemtuzumabisapprovedinAustralia,theEuropeanUnion,andMexicofortreatmentofactiveRRMSdefinedbyclinicalorimagingfeatures,inBrazilfortreatmentofrelapsingformsofMS,andinCanadaforpatientswithinadequateresponsetointerferonbetaorotherDMTs.Rebif®isaregisteredtrademarkofEMDSerono,Inc.*Deceased.

Sustained Improvement in Disability Outcomes with Alemtuzumab in Active Relapsing-Remitting Multiple Sclerosis Patients Who Participated in CARE-MS II: Three-Year Follow-up

G Giovannoni,1DHMargolin,2 J Palmer,2 J Herbert3

1QueenMaryUniversityofLondon,BartsandTheLondonSchoolofMedicine,London,UK;2Genzyme,aSanoficompany,Cambridge,MA,USA;3NewYorkUniversityMedicalCenter,NewYork,NY,USA

Presented at the 66th Annual Meeting of the American Academy of Neurology (AAN), April 26–May 03, 2014, Philadelphia, PA

P3.165

Figure 2. Mean EDSS Change: Proportion Improved, Remained Stable, or Worsened in Patients Who Had Received Alemtuzumab 12 mg in the Core Study

• AtYear3,66%ofalemtuzumab-treatedpatientshadeitherstableorimprovedEDSSscores from extension study baseline (data not shown)

• AmongpatientswhoseEDSSscoreremainedstablefrombaselinetoYear2,75%eithercontinuedtoremainstableorexperiencedimprovementfromYears2–3(Figure 3)

• AmongpatientswhoseEDSSscoreimprovedfrombaselinetoYear2,58%remainedstableorimprovedfurtherfromYears2–3(Figure 3)

Sustained Reduction in Preexisting Disability• AtYear3,morethanonethirdofpatientswhohadreceivedalemtuzumab12mginthecorestudyattainedimprovementinpreexistingdisabilitysustainedfor6months,asmeasured by 6-month sustained reduction in disability (Figure 4) – Aboutonequarterofthepatientsachieved12-monthsustainedreductionindisability

at Year 3

Durability of Effect • MeanEDSSscoreatYear3was2.5forpatientswhoreceived2coursesofalemtuzumab

over 3 years – Year3meanEDSSscorechangefromcorestudybaselinewas−0.16inthispatientsubgroup

• AtYear3,EDSSscorewasimprovedfromcorestudybaselinein48%ofpatientswhoreceived2coursesofalemtuzumabover3yearsandstableinafurther28%ofpatients(data not shown)

• AmongpatientswhoseEDSSscoreremainedstablefrombaselinetoYear2,79%eithercontinuedtoremainstableorexperiencedimprovementfromYears2–3(Figure 5)

• AmongpatientswhoseEDSSscoreimprovedfrombaselinetoYear2,61%remainedstableorimprovedfurtherfromYears2–3(Figure 5)

Sustained Reduction in Preexisting Disability• Forpatientswhoreceivedonly2coursesofalemtuzumabover3years,theproportionsachieving3-,6-,and12-monthsustainedreductionindisabilitywere45%,37%,and28% at Year 3 (data not shown)

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;EDSS=ExpandedDisabilityStatusScale.

EDSS=ExpandedDisabilityStatusScale

Figure 1. EDSS Score over Time in the Core Study and Extension

0 6 12 18 24 30 363 9 15 21 27 33

426 419 422 410 416 373 370419 419 415 413 367 364

0

2.00

2.40

2.60

2.20

2.80Baseline EDSS

3.00

Follow-up MonthNo. of Patients

EDSS

Sco

re

Alemtuzumab 12 mg

CARE-MS II Core Study Extension

(N=423)Years 0–2

(N=369)Years 0–3

Prop

ortio

n of

Pat

ient

s (%

)

60 Improved

Remained stable

Worsened50

40

30

20

10

0

46

302524

30

45

(N=178)

ImprovedYears 0–2

EDSS Shift Category (Baseline through Year 2)(N=112)

Remained stableYears 0–2

Prop

ortio

n of

Pat

ient

sat

Yea

r 3 (%

) 60

70

80 Improved from Year 2 to Year 3

Remained Stable from Year 2 to Year 3

50

40

30

20

10

011.8

46.651.8

23.2

Figure 3. EDSS Improvement from Year 2 to Year 3 in Alemtuzumab-treated Patients Who Improved or Remained Stable from Baseline to Year 2

EDSS=ExpandedDisabilityStatusScale

35%

43%

0 6 12 18 24 30 360

10

20

30

40

50

Follow-up Month

CARE-MS II Core Study Extension

321 280 241 222 200 172 1623-Month SRD

Prop

ortio

n of

Pat

ient

s w

ith S

usta

ined

R

educ

tion

in D

isab

ility

(%)

29%35%

321 290 262 245 221 190 1826-Month SRD

22%27%

321 294 275 263 245 215 20712-Month SRD

No. at Risk

Figure 4. Percentage of Patients with 3-, 6-, and 12-Month Sustained Reduction in Disability

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;SRD=sustainedreductionindisability

Figure 5. EDSS Improvement from Year 2 to Year 3 in Patients Treated with 2 Courses of Alemtuzumab over 3 Years Who Improved or Remained Stable from Baseline to Year 2

EDSS=ExpandedDisabilityStatusScale

(N=148)

ImprovedYears 0–2

EDSS Shift Category (Baseline through Year 2)(N=96)

Remained stableYears 0–2

Prop

ortio

n of

Pat

ient

sat

Yea

r 3 (%

) 60

70

80 Improved from Year 2 to Year 3

Remained Stable from Year 2 to Year 3

50

40

30

20

10

012.2

48.654.2

25.0

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;EDSS=ExpandedDisabilityStatusScale

REFERENCES1. Hu Y, et al. Immunology 2009;128:260-70. 2. Weber MS, Hemmer B. Results Probl Cell Differ 2010;51:115-26. 3. Havari E, et al. Immunology 2014;141:123-31. 4. Cox AL, et al. Eur J Immunol 2005;35:3332-42. 5. Coles AJ, et al. N Engl J Med 2008;359:1786-801. 6. Cohen JA, et al. Lancet 2012;380:1819-28. 7. Coles AJ, et al. Lancet 2012;380:1829-39. 8. Graves J, et al. Neurology 2013;30 (abstract P3.158). 9. Fox EJ, et al. Neurology 2013;30 (abstract S41.001).

CONCLUSIONS• Interim data from the CARE-MS II extension study demonstrate that alemtuzumabhasdurableefficacyondisabilitythrough3yearsinpatientswhohadrelapsedonpriortherapy,despitethemajorityofpatientsreceivingnoadditionalalemtuzumabtreatmentcoursesorotherDMTs – AlmosthalfofalemtuzumabpatientsdemonstratedimproveddisabilityscoresatYear3comparedwiththatatstudybaseline

– Morethanonethirdofformeralemtuzumabpatientsattainedsustaineddisabilityimprovement(6-monthsustainedreductionindisability) by Year 3

– Similardisabilityoutcomeswereobservedinpatientswhoreceivedonly 2 treatment courses over 3 years

• Thesefindings,togetherwithpreviouslyreporteddata,supportthepositivebenefit-riskprofileforalemtuzumabasapotentialtreatmentforRRMSinpatientswhorelapsedonpriortherapy

INTRODUCTION• AlemtuzumabisahumanizedmonoclonalantibodyapprovedinAustralia,Brazil,Canada,theEuropeanUnion,andMexicoforthetreatmentofactiverelapsing-remittingmultiplesclerosis(RRMS)thatselectivelytargetsCD52,resultingindepletionandsubsequentrepopulationofcirculatingTandBlymphocytes1-4

• Alemtuzumab,administeredin2annualcourses,hasdemonstratedsuperiorefficacyvs.high-dosesubcutaneousinterferonbeta-1a(SCIFNB-1a)intreatment-naiveRRMSpatients(CAMMS223[NCT00050778];ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis[CARE-MS]I[NCT00530348])5,6;andinpatientswhorelapsedonapriortherapy(CARE-MSII[NCT00548405])7 – Intheseclinicaltrials,alemtuzumabhadaconsistentandmanageablesafetyprofile,withthemostcommonadverseevents(AEs)beinginfusion-associatedreactions,non-serious infections, and autoimmune AEs

• InCARE-MSII,alemtuzumabsignificantlyreduced6-monthsustainedaccumulationofdisabilityat2yearsby49%beyondthatwithSCIFNB-1a(p<0.0001),andalemtuzumabpatientsweremorethantwiceaslikelytodemonstrate6-monthsustainedimprovementinpreexistingdisability(hazardratio2.57;p=0.0002)7 – PatientstreatedwithalemtuzumabalsohadsignificantlyimprovedvisualoutcomesusingSloanlow-contrastacuitymetrics,andfunctionaloutcomesusingMultipleSclerosisFunctionalComposite,comparedwithSCIFNB-1aatYear2(p<0.05)7,8

OBJECTIVE• ThepresentstudyexaminedthedurabilityofdisabilityimprovementinYear3follow-upduringanongoingextensionstudy(NCT00930553)ofalemtuzumabpatientswhorelapsedonapriortherapy

METHODSStudy DesignCore Study7

• CARE-MSIIwasarandomized,rater-blinded,active-controlled,head-to-head,phase3trial of 24 months’ duration

• Entrycriteriaincludedage18–55years,baselineExpandedDisabilityStatusScale(EDSS)score ≤5,MSsymptomonsetwithin10years,activeRRMS(≥2relapsesinprior2yearsand ≥1intheprioryear),andrelapseonpriortherapy(≥1relapseduringtreatmentwithIFNBorglatirameracetate,afterreceivingthattherapyfor≥6months[priortreatmentwithothertherapieswasalsopermitted])

• Patientswererandomized2:1toreceivealemtuzumab12mg/dayviaintravenous(IV)infusions on 5 consecutive days at baseline and on 3 consecutive days 12 months later, or SCIFNB-1a44µg3timesweekly

Extension Study9

• Patients who had received alemtuzumab in the core study received re-treatment as neededintheextension(12mg/dayIVon3consecutivedays) – Re-treatmentcriteriawereoneofthefollowing,basedontheinvestigator’sclinical

decision: ■ ≥1protocol-definedrelapse ■ ≥2neworenlargingT2and/orgadolinium-enhancingbrainorspinallesionsonmagneticresonanceimaging

– Useofotherdisease-modifyingtherapies(DMTs)wasallowedbasedoninvestigators’clinical decisions

– AlldatapresentedherearefrompatientswhoreceivedalemtuzumabinthecoreCARE-MS II study

Disability Assessment• EDSSwasassessedbyblindedratersatcorestudybaselineandevery3months• Disabilityoutcomes

– ChangefromcorestudybaselineonEDSS – Proportionofpatientsimproved,remainedstable,orworsenedonEDSS

■ Improvementandworseningweredefinedas≥0.5-pointdecreaseorincrease,respectively,fromcorestudybaselineEDSSscore

– Sustained reduction in disability: decrease from core study baseline by ≥1EDSSpointconfirmedover3,6,or12monthsforpatientswithbaselineEDSSscores≥2.0

Statistical Analysis• AnalyseswerebasedonYear3follow-updataonpatientswhohadreceivedalemtuzumab12mginthecoreCARE-MSIIstudy

• DatafromCARE-MSIIpatientswhotransitionedintotheextensionstudywereanalyzedfromthetimeoffirsttreatment

• Kaplan-Meieranalysisoftimeto3-,6-,and12-monthsustainedreductionindisability• Analyseswereundertakenforallpatientsintheextensionandforpatientswhoreceived

only 2 courses over 3 years

RESULTSPatients• Morethan90%(393of423)ofpatientswhohadreceivedalemtuzumab12mginCARE-MSIIandcompletedthecorestudyenteredtheextension

• Approximately80%didnotreceivere-treatmentduringYear3• Fewerthan3%offormeralemtuzumab-treatedpatientsreceivedanotherDMTinYear3Disability Improvement • MeanEDSSscoreswere2.7atcorestudybaseline,2.5atYear2,and2.6atYear3(Figure 1)

• MeanEDSSscoresremainedbelowpre-treatmentvaluesduringthethirdyear – Year2meanEDSSscorechangefromcorestudybaseline:−0.21 – Year3meanEDSSscorechangefromcorestudybaseline:−0.06

• AtYear3,70%ofalemtuzumab-treatedpatientshadeitherstableorimprovedEDSSscores from core study baseline (Figure 2),similartotheresultsseenoverYears0–2

Acknowledgments and DisclosuresCARE-MSIIsteeringcommittee:DouglasLArnold,JeffreyACohen,AlasdairJColes,DAlastairSCompston,ChristianConfavreux*,EdwardFox,Hans-PeterHartung,EvaHavrdova,TamaraMiller,KrzysztofWSelmaj,CaryLTwyman,andHowardWeiner.Genzyme:AjiNair;LindaKasten.CARE-MSIIwassponsoredbyGenzyme,aSanoficompany,andBayerHealthcarePharmaceuticals.EditorialsupportforthisposterwasprovidedbyRichardHogan,EvidenceScientificSolutions,andwasfundedbyGenzyme.G.G.reportsreceivingcompensationforconsulting,servingonascientificadvisoryboard,speaking,orotheractivitiesfromBiogen-Idec,FivePrimeTherapeutics,Genzyme,GWPharma,Merck-Serono,Novartis,Roche,Synthon,Teva,andVertexPharmaceuticals.G.G.receivedcompensationforservingasajournaleditorforMultiple Sclerosis and Related DisordersandresearchsupportfromSerono.D.H.MandJ.P.reportreceivingpersonalcompensationasemployeesofGenzyme.J.H.reportsreceivingpersonalcompensationforconsulting,servingonascientificadvisoryboard,speaking,orotheractivitiesfromBiogenIdec.AlemtuzumabisapprovedinAustralia,theEuropeanUnion,andMexicofortreatmentofactiveRRMSdefinedbyclinicalorimagingfeatures,inBrazilfortreatmentofrelapsingformsofMS,andinCanadaforpatientswithinadequateresponsetointerferonbetaorotherDMTs.Rebif®isaregisteredtrademarkofEMDSerono,Inc.*Deceased.

Sustained Improvement in Disability Outcomes with Alemtuzumab in Active Relapsing-Remitting Multiple Sclerosis Patients Who Participated in CARE-MS II: Three-Year Follow-up

G Giovannoni,1DHMargolin,2 J Palmer,2 J Herbert3

1QueenMaryUniversityofLondon,BartsandTheLondonSchoolofMedicine,London,UK;2Genzyme,aSanoficompany,Cambridge,MA,USA;3NewYorkUniversityMedicalCenter,NewYork,NY,USA

Presented at the 66th Annual Meeting of the American Academy of Neurology (AAN), April 26–May 03, 2014, Philadelphia, PA

P3.165

Figure 2. Mean EDSS Change: Proportion Improved, Remained Stable, or Worsened in Patients Who Had Received Alemtuzumab 12 mg in the Core Study

• AtYear3,66%ofalemtuzumab-treatedpatientshadeitherstableorimprovedEDSSscores from extension study baseline (data not shown)

• AmongpatientswhoseEDSSscoreremainedstablefrombaselinetoYear2,75%eithercontinuedtoremainstableorexperiencedimprovementfromYears2–3(Figure 3)

• AmongpatientswhoseEDSSscoreimprovedfrombaselinetoYear2,58%remainedstableorimprovedfurtherfromYears2–3(Figure 3)

Sustained Reduction in Preexisting Disability• AtYear3,morethanonethirdofpatientswhohadreceivedalemtuzumab12mginthecorestudyattainedimprovementinpreexistingdisabilitysustainedfor6months,asmeasured by 6-month sustained reduction in disability (Figure 4) – Aboutonequarterofthepatientsachieved12-monthsustainedreductionindisability

at Year 3

Durability of Effect • MeanEDSSscoreatYear3was2.5forpatientswhoreceived2coursesofalemtuzumab

over 3 years – Year3meanEDSSscorechangefromcorestudybaselinewas−0.16inthispatientsubgroup

• AtYear3,EDSSscorewasimprovedfromcorestudybaselinein48%ofpatientswhoreceived2coursesofalemtuzumabover3yearsandstableinafurther28%ofpatients(data not shown)

• AmongpatientswhoseEDSSscoreremainedstablefrombaselinetoYear2,79%eithercontinuedtoremainstableorexperiencedimprovementfromYears2–3(Figure 5)

• AmongpatientswhoseEDSSscoreimprovedfrombaselinetoYear2,61%remainedstableorimprovedfurtherfromYears2–3(Figure 5)

Sustained Reduction in Preexisting Disability• Forpatientswhoreceivedonly2coursesofalemtuzumabover3years,theproportionsachieving3-,6-,and12-monthsustainedreductionindisabilitywere45%,37%,and28% at Year 3 (data not shown)

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;EDSS=ExpandedDisabilityStatusScale.

EDSS=ExpandedDisabilityStatusScale

Figure 1. EDSS Score over Time in the Core Study and Extension

0 6 12 18 24 30 363 9 15 21 27 33

426 419 422 410 416 373 370419 419 415 413 367 364

0

2.00

2.40

2.60

2.20

2.80Baseline EDSS

3.00

Follow-up MonthNo. of Patients

EDSS

Sco

re

Alemtuzumab 12 mg

CARE-MS II Core Study Extension

(N=423)Years 0–2

(N=369)Years 0–3

Prop

ortio

n of

Pat

ient

s (%

)

60 Improved

Remained stable

Worsened50

40

30

20

10

0

46

302524

30

45

(N=178)

ImprovedYears 0–2

EDSS Shift Category (Baseline through Year 2)(N=112)

Remained stableYears 0–2

Prop

ortio

n of

Pat

ient

sat

Yea

r 3 (%

) 60

70

80 Improved from Year 2 to Year 3

Remained Stable from Year 2 to Year 3

50

40

30

20

10

011.8

46.651.8

23.2

Figure 3. EDSS Improvement from Year 2 to Year 3 in Alemtuzumab-treated Patients Who Improved or Remained Stable from Baseline to Year 2

EDSS=ExpandedDisabilityStatusScale

35%

43%

0 6 12 18 24 30 360

10

20

30

40

50

Follow-up Month

CARE-MS II Core Study Extension

321 280 241 222 200 172 1623-Month SRD

Prop

ortio

n of

Pat

ient

s w

ith S

usta

ined

R

educ

tion

in D

isab

ility

(%)

29%35%

321 290 262 245 221 190 1826-Month SRD

22%27%

321 294 275 263 245 215 20712-Month SRD

No. at Risk

Figure 4. Percentage of Patients with 3-, 6-, and 12-Month Sustained Reduction in Disability

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;SRD=sustainedreductionindisability

Figure 5. EDSS Improvement from Year 2 to Year 3 in Patients Treated with 2 Courses of Alemtuzumab over 3 Years Who Improved or Remained Stable from Baseline to Year 2

EDSS=ExpandedDisabilityStatusScale

(N=148)

ImprovedYears 0–2

EDSS Shift Category (Baseline through Year 2)(N=96)

Remained stableYears 0–2

Prop

ortio

n of

Pat

ient

sat

Yea

r 3 (%

) 60

70

80 Improved from Year 2 to Year 3

Remained Stable from Year 2 to Year 3

50

40

30

20

10

012.2

48.654.2

25.0

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;EDSS=ExpandedDisabilityStatusScale

REFERENCES1. Hu Y, et al. Immunology 2009;128:260-70. 2. Weber MS, Hemmer B. Results Probl Cell Differ 2010;51:115-26. 3. Havari E, et al. Immunology 2014;141:123-31. 4. Cox AL, et al. Eur J Immunol 2005;35:3332-42. 5. Coles AJ, et al. N Engl J Med 2008;359:1786-801. 6. Cohen JA, et al. Lancet 2012;380:1819-28. 7. Coles AJ, et al. Lancet 2012;380:1829-39. 8. Graves J, et al. Neurology 2013;30 (abstract P3.158). 9. Fox EJ, et al. Neurology 2013;30 (abstract S41.001).

CONCLUSIONS• Interim data from the CARE-MS II extension study demonstrate that alemtuzumabhasdurableefficacyondisabilitythrough3yearsinpatientswhohadrelapsedonpriortherapy,despitethemajorityofpatientsreceivingnoadditionalalemtuzumabtreatmentcoursesorotherDMTs – AlmosthalfofalemtuzumabpatientsdemonstratedimproveddisabilityscoresatYear3comparedwiththatatstudybaseline

– Morethanonethirdofformeralemtuzumabpatientsattainedsustaineddisabilityimprovement(6-monthsustainedreductionindisability) by Year 3

– Similardisabilityoutcomeswereobservedinpatientswhoreceivedonly 2 treatment courses over 3 years

• Thesefindings,togetherwithpreviouslyreporteddata,supportthepositivebenefit-riskprofileforalemtuzumabasapotentialtreatmentforRRMSinpatientswhorelapsedonpriortherapy

INTRODUCTION• AlemtuzumabisahumanizedmonoclonalantibodyapprovedinAustralia,Brazil,Canada,theEuropeanUnion,andMexicoforthetreatmentofactiverelapsing-remittingmultiplesclerosis(RRMS)thatselectivelytargetsCD52,resultingindepletionandsubsequentrepopulationofcirculatingTandBlymphocytes1-4

• Alemtuzumab,administeredin2annualcourses,hasdemonstratedsuperiorefficacyvs.high-dosesubcutaneousinterferonbeta-1a(SCIFNB-1a)intreatment-naiveRRMSpatients(CAMMS223[NCT00050778];ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis[CARE-MS]I[NCT00530348])5,6;andinpatientswhorelapsedonapriortherapy(CARE-MSII[NCT00548405])7 – Intheseclinicaltrials,alemtuzumabhadaconsistentandmanageablesafetyprofile,withthemostcommonadverseevents(AEs)beinginfusion-associatedreactions,non-serious infections, and autoimmune AEs

• InCARE-MSII,alemtuzumabsignificantlyreduced6-monthsustainedaccumulationofdisabilityat2yearsby49%beyondthatwithSCIFNB-1a(p<0.0001),andalemtuzumabpatientsweremorethantwiceaslikelytodemonstrate6-monthsustainedimprovementinpreexistingdisability(hazardratio2.57;p=0.0002)7 – PatientstreatedwithalemtuzumabalsohadsignificantlyimprovedvisualoutcomesusingSloanlow-contrastacuitymetrics,andfunctionaloutcomesusingMultipleSclerosisFunctionalComposite,comparedwithSCIFNB-1aatYear2(p<0.05)7,8

OBJECTIVE• ThepresentstudyexaminedthedurabilityofdisabilityimprovementinYear3follow-upduringanongoingextensionstudy(NCT00930553)ofalemtuzumabpatientswhorelapsedonapriortherapy

METHODSStudy DesignCore Study7

• CARE-MSIIwasarandomized,rater-blinded,active-controlled,head-to-head,phase3trial of 24 months’ duration

• Entrycriteriaincludedage18–55years,baselineExpandedDisabilityStatusScale(EDSS)score ≤5,MSsymptomonsetwithin10years,activeRRMS(≥2relapsesinprior2yearsand ≥1intheprioryear),andrelapseonpriortherapy(≥1relapseduringtreatmentwithIFNBorglatirameracetate,afterreceivingthattherapyfor≥6months[priortreatmentwithothertherapieswasalsopermitted])

• Patientswererandomized2:1toreceivealemtuzumab12mg/dayviaintravenous(IV)infusions on 5 consecutive days at baseline and on 3 consecutive days 12 months later, or SCIFNB-1a44µg3timesweekly

Extension Study9

• Patients who had received alemtuzumab in the core study received re-treatment as neededintheextension(12mg/dayIVon3consecutivedays) – Re-treatmentcriteriawereoneofthefollowing,basedontheinvestigator’sclinical

decision: ■ ≥1protocol-definedrelapse ■ ≥2neworenlargingT2and/orgadolinium-enhancingbrainorspinallesionsonmagneticresonanceimaging

– Useofotherdisease-modifyingtherapies(DMTs)wasallowedbasedoninvestigators’clinical decisions

– AlldatapresentedherearefrompatientswhoreceivedalemtuzumabinthecoreCARE-MS II study

Disability Assessment• EDSSwasassessedbyblindedratersatcorestudybaselineandevery3months• Disabilityoutcomes

– ChangefromcorestudybaselineonEDSS – Proportionofpatientsimproved,remainedstable,orworsenedonEDSS

■ Improvementandworseningweredefinedas≥0.5-pointdecreaseorincrease,respectively,fromcorestudybaselineEDSSscore

– Sustained reduction in disability: decrease from core study baseline by ≥1EDSSpointconfirmedover3,6,or12monthsforpatientswithbaselineEDSSscores≥2.0

Statistical Analysis• AnalyseswerebasedonYear3follow-updataonpatientswhohadreceivedalemtuzumab12mginthecoreCARE-MSIIstudy

• DatafromCARE-MSIIpatientswhotransitionedintotheextensionstudywereanalyzedfromthetimeoffirsttreatment

• Kaplan-Meieranalysisoftimeto3-,6-,and12-monthsustainedreductionindisability• Analyseswereundertakenforallpatientsintheextensionandforpatientswhoreceived

only 2 courses over 3 years

RESULTSPatients• Morethan90%(393of423)ofpatientswhohadreceivedalemtuzumab12mginCARE-MSIIandcompletedthecorestudyenteredtheextension

• Approximately80%didnotreceivere-treatmentduringYear3• Fewerthan3%offormeralemtuzumab-treatedpatientsreceivedanotherDMTinYear3Disability Improvement • MeanEDSSscoreswere2.7atcorestudybaseline,2.5atYear2,and2.6atYear3(Figure 1)

• MeanEDSSscoresremainedbelowpre-treatmentvaluesduringthethirdyear – Year2meanEDSSscorechangefromcorestudybaseline:−0.21 – Year3meanEDSSscorechangefromcorestudybaseline:−0.06

• AtYear3,70%ofalemtuzumab-treatedpatientshadeitherstableorimprovedEDSSscores from core study baseline (Figure 2),similartotheresultsseenoverYears0–2

Acknowledgments and DisclosuresCARE-MSIIsteeringcommittee:DouglasLArnold,JeffreyACohen,AlasdairJColes,DAlastairSCompston,ChristianConfavreux*,EdwardFox,Hans-PeterHartung,EvaHavrdova,TamaraMiller,KrzysztofWSelmaj,CaryLTwyman,andHowardWeiner.Genzyme:AjiNair;LindaKasten.CARE-MSIIwassponsoredbyGenzyme,aSanoficompany,andBayerHealthcarePharmaceuticals.EditorialsupportforthisposterwasprovidedbyRichardHogan,EvidenceScientificSolutions,andwasfundedbyGenzyme.G.G.reportsreceivingcompensationforconsulting,servingonascientificadvisoryboard,speaking,orotheractivitiesfromBiogen-Idec,FivePrimeTherapeutics,Genzyme,GWPharma,Merck-Serono,Novartis,Roche,Synthon,Teva,andVertexPharmaceuticals.G.G.receivedcompensationforservingasajournaleditorforMultiple Sclerosis and Related DisordersandresearchsupportfromSerono.D.H.MandJ.P.reportreceivingpersonalcompensationasemployeesofGenzyme.J.H.reportsreceivingpersonalcompensationforconsulting,servingonascientificadvisoryboard,speaking,orotheractivitiesfromBiogenIdec.AlemtuzumabisapprovedinAustralia,theEuropeanUnion,andMexicofortreatmentofactiveRRMSdefinedbyclinicalorimagingfeatures,inBrazilfortreatmentofrelapsingformsofMS,andinCanadaforpatientswithinadequateresponsetointerferonbetaorotherDMTs.Rebif®isaregisteredtrademarkofEMDSerono,Inc.*Deceased.

Sustained Improvement in Disability Outcomes with Alemtuzumab in Active Relapsing-Remitting Multiple Sclerosis Patients Who Participated in CARE-MS II: Three-Year Follow-up

G Giovannoni,1DHMargolin,2 J Palmer,2 J Herbert3

1QueenMaryUniversityofLondon,BartsandTheLondonSchoolofMedicine,London,UK;2Genzyme,aSanoficompany,Cambridge,MA,USA;3NewYorkUniversityMedicalCenter,NewYork,NY,USA

Presented at the 66th Annual Meeting of the American Academy of Neurology (AAN), April 26–May 03, 2014, Philadelphia, PA

P3.165

Figure 2. Mean EDSS Change: Proportion Improved, Remained Stable, or Worsened in Patients Who Had Received Alemtuzumab 12 mg in the Core Study

• AtYear3,66%ofalemtuzumab-treatedpatientshadeitherstableorimprovedEDSSscores from extension study baseline (data not shown)

• AmongpatientswhoseEDSSscoreremainedstablefrombaselinetoYear2,75%eithercontinuedtoremainstableorexperiencedimprovementfromYears2–3(Figure 3)

• AmongpatientswhoseEDSSscoreimprovedfrombaselinetoYear2,58%remainedstableorimprovedfurtherfromYears2–3(Figure 3)

Sustained Reduction in Preexisting Disability• AtYear3,morethanonethirdofpatientswhohadreceivedalemtuzumab12mginthecorestudyattainedimprovementinpreexistingdisabilitysustainedfor6months,asmeasured by 6-month sustained reduction in disability (Figure 4) – Aboutonequarterofthepatientsachieved12-monthsustainedreductionindisability

at Year 3

Durability of Effect • MeanEDSSscoreatYear3was2.5forpatientswhoreceived2coursesofalemtuzumab

over 3 years – Year3meanEDSSscorechangefromcorestudybaselinewas−0.16inthispatientsubgroup

• AtYear3,EDSSscorewasimprovedfromcorestudybaselinein48%ofpatientswhoreceived2coursesofalemtuzumabover3yearsandstableinafurther28%ofpatients(data not shown)

• AmongpatientswhoseEDSSscoreremainedstablefrombaselinetoYear2,79%eithercontinuedtoremainstableorexperiencedimprovementfromYears2–3(Figure 5)

• AmongpatientswhoseEDSSscoreimprovedfrombaselinetoYear2,61%remainedstableorimprovedfurtherfromYears2–3(Figure 5)

Sustained Reduction in Preexisting Disability• Forpatientswhoreceivedonly2coursesofalemtuzumabover3years,theproportionsachieving3-,6-,and12-monthsustainedreductionindisabilitywere45%,37%,and28% at Year 3 (data not shown)

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;EDSS=ExpandedDisabilityStatusScale.

EDSS=ExpandedDisabilityStatusScale

Figure 1. EDSS Score over Time in the Core Study and Extension

0 6 12 18 24 30 363 9 15 21 27 33

426 419 422 410 416 373 370419 419 415 413 367 364

0

2.00

2.40

2.60

2.20

2.80Baseline EDSS

3.00

Follow-up MonthNo. of Patients

EDSS

Sco

re

Alemtuzumab 12 mg

CARE-MS II Core Study Extension

(N=423)Years 0–2

(N=369)Years 0–3

Prop

ortio

n of

Pat

ient

s (%

)

60 Improved

Remained stable

Worsened50

40

30

20

10

0

46

302524

30

45

(N=178)

ImprovedYears 0–2

EDSS Shift Category (Baseline through Year 2)(N=112)

Remained stableYears 0–2

Prop

ortio

n of

Pat

ient

sat

Yea

r 3 (%

) 60

70

80 Improved from Year 2 to Year 3

Remained Stable from Year 2 to Year 3

50

40

30

20

10

011.8

46.651.8

23.2

Figure 3. EDSS Improvement from Year 2 to Year 3 in Alemtuzumab-treated Patients Who Improved or Remained Stable from Baseline to Year 2

EDSS=ExpandedDisabilityStatusScale

35%

43%

0 6 12 18 24 30 360

10

20

30

40

50

Follow-up Month

CARE-MS II Core Study Extension

321 280 241 222 200 172 1623-Month SRD

Prop

ortio

n of

Pat

ient

s w

ith S

usta

ined

R

educ

tion

in D

isab

ility

(%)

29%35%

321 290 262 245 221 190 1826-Month SRD

22%27%

321 294 275 263 245 215 20712-Month SRD

No. at Risk

Figure 4. Percentage of Patients with 3-, 6-, and 12-Month Sustained Reduction in Disability

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;SRD=sustainedreductionindisability

Figure 5. EDSS Improvement from Year 2 to Year 3 in Patients Treated with 2 Courses of Alemtuzumab over 3 Years Who Improved or Remained Stable from Baseline to Year 2

EDSS=ExpandedDisabilityStatusScale

(N=148)

ImprovedYears 0–2

EDSS Shift Category (Baseline through Year 2)(N=96)

Remained stableYears 0–2

Prop

ortio

n of

Pat

ient

sat

Yea

r 3 (%

) 60

70

80 Improved from Year 2 to Year 3

Remained Stable from Year 2 to Year 3

50

40

30

20

10

012.2

48.654.2

25.0

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;EDSS=ExpandedDisabilityStatusScale

REFERENCES1. Hu Y, et al. Immunology 2009;128:260-70. 2. Weber MS, Hemmer B. Results Probl Cell Differ 2010;51:115-26. 3. Havari E, et al. Immunology 2014;141:123-31. 4. Cox AL, et al. Eur J Immunol 2005;35:3332-42. 5. Coles AJ, et al. N Engl J Med 2008;359:1786-801. 6. Cohen JA, et al. Lancet 2012;380:1819-28. 7. Coles AJ, et al. Lancet 2012;380:1829-39. 8. Graves J, et al. Neurology 2013;30 (abstract P3.158). 9. Fox EJ, et al. Neurology 2013;30 (abstract S41.001).

CONCLUSIONS• Interim data from the CARE-MS II extension study demonstrate that alemtuzumabhasdurableefficacyondisabilitythrough3yearsinpatientswhohadrelapsedonpriortherapy,despitethemajorityofpatientsreceivingnoadditionalalemtuzumabtreatmentcoursesorotherDMTs – AlmosthalfofalemtuzumabpatientsdemonstratedimproveddisabilityscoresatYear3comparedwiththatatstudybaseline

– Morethanonethirdofformeralemtuzumabpatientsattainedsustaineddisabilityimprovement(6-monthsustainedreductionindisability) by Year 3

– Similardisabilityoutcomeswereobservedinpatientswhoreceivedonly 2 treatment courses over 3 years

• Thesefindings,togetherwithpreviouslyreporteddata,supportthepositivebenefit-riskprofileforalemtuzumabasapotentialtreatmentforRRMSinpatientswhorelapsedonpriortherapy

INTRODUCTION• AlemtuzumabisahumanizedmonoclonalantibodyapprovedinAustralia,Brazil,Canada,theEuropeanUnion,andMexicoforthetreatmentofactiverelapsing-remittingmultiplesclerosis(RRMS)thatselectivelytargetsCD52,resultingindepletionandsubsequentrepopulationofcirculatingTandBlymphocytes1-4

• Alemtuzumab,administeredin2annualcourses,hasdemonstratedsuperiorefficacyvs.high-dosesubcutaneousinterferonbeta-1a(SCIFNB-1a)intreatment-naiveRRMSpatients(CAMMS223[NCT00050778];ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis[CARE-MS]I[NCT00530348])5,6;andinpatientswhorelapsedonapriortherapy(CARE-MSII[NCT00548405])7 – Intheseclinicaltrials,alemtuzumabhadaconsistentandmanageablesafetyprofile,withthemostcommonadverseevents(AEs)beinginfusion-associatedreactions,non-serious infections, and autoimmune AEs

• InCARE-MSII,alemtuzumabsignificantlyreduced6-monthsustainedaccumulationofdisabilityat2yearsby49%beyondthatwithSCIFNB-1a(p<0.0001),andalemtuzumabpatientsweremorethantwiceaslikelytodemonstrate6-monthsustainedimprovementinpreexistingdisability(hazardratio2.57;p=0.0002)7 – PatientstreatedwithalemtuzumabalsohadsignificantlyimprovedvisualoutcomesusingSloanlow-contrastacuitymetrics,andfunctionaloutcomesusingMultipleSclerosisFunctionalComposite,comparedwithSCIFNB-1aatYear2(p<0.05)7,8

OBJECTIVE• ThepresentstudyexaminedthedurabilityofdisabilityimprovementinYear3follow-upduringanongoingextensionstudy(NCT00930553)ofalemtuzumabpatientswhorelapsedonapriortherapy

METHODSStudy DesignCore Study7

• CARE-MSIIwasarandomized,rater-blinded,active-controlled,head-to-head,phase3trial of 24 months’ duration

• Entrycriteriaincludedage18–55years,baselineExpandedDisabilityStatusScale(EDSS)score ≤5,MSsymptomonsetwithin10years,activeRRMS(≥2relapsesinprior2yearsand ≥1intheprioryear),andrelapseonpriortherapy(≥1relapseduringtreatmentwithIFNBorglatirameracetate,afterreceivingthattherapyfor≥6months[priortreatmentwithothertherapieswasalsopermitted])

• Patientswererandomized2:1toreceivealemtuzumab12mg/dayviaintravenous(IV)infusions on 5 consecutive days at baseline and on 3 consecutive days 12 months later, or SCIFNB-1a44µg3timesweekly

Extension Study9

• Patients who had received alemtuzumab in the core study received re-treatment as neededintheextension(12mg/dayIVon3consecutivedays) – Re-treatmentcriteriawereoneofthefollowing,basedontheinvestigator’sclinical

decision: ■ ≥1protocol-definedrelapse ■ ≥2neworenlargingT2and/orgadolinium-enhancingbrainorspinallesionsonmagneticresonanceimaging

– Useofotherdisease-modifyingtherapies(DMTs)wasallowedbasedoninvestigators’clinical decisions

– AlldatapresentedherearefrompatientswhoreceivedalemtuzumabinthecoreCARE-MS II study

Disability Assessment• EDSSwasassessedbyblindedratersatcorestudybaselineandevery3months• Disabilityoutcomes

– ChangefromcorestudybaselineonEDSS – Proportionofpatientsimproved,remainedstable,orworsenedonEDSS

■ Improvementandworseningweredefinedas≥0.5-pointdecreaseorincrease,respectively,fromcorestudybaselineEDSSscore

– Sustained reduction in disability: decrease from core study baseline by ≥1EDSSpointconfirmedover3,6,or12monthsforpatientswithbaselineEDSSscores≥2.0

Statistical Analysis• AnalyseswerebasedonYear3follow-updataonpatientswhohadreceivedalemtuzumab12mginthecoreCARE-MSIIstudy

• DatafromCARE-MSIIpatientswhotransitionedintotheextensionstudywereanalyzedfromthetimeoffirsttreatment

• Kaplan-Meieranalysisoftimeto3-,6-,and12-monthsustainedreductionindisability• Analyseswereundertakenforallpatientsintheextensionandforpatientswhoreceived

only 2 courses over 3 years

RESULTSPatients• Morethan90%(393of423)ofpatientswhohadreceivedalemtuzumab12mginCARE-MSIIandcompletedthecorestudyenteredtheextension

• Approximately80%didnotreceivere-treatmentduringYear3• Fewerthan3%offormeralemtuzumab-treatedpatientsreceivedanotherDMTinYear3Disability Improvement • MeanEDSSscoreswere2.7atcorestudybaseline,2.5atYear2,and2.6atYear3(Figure 1)

• MeanEDSSscoresremainedbelowpre-treatmentvaluesduringthethirdyear – Year2meanEDSSscorechangefromcorestudybaseline:−0.21 – Year3meanEDSSscorechangefromcorestudybaseline:−0.06

• AtYear3,70%ofalemtuzumab-treatedpatientshadeitherstableorimprovedEDSSscores from core study baseline (Figure 2),similartotheresultsseenoverYears0–2

Acknowledgments and DisclosuresCARE-MSIIsteeringcommittee:DouglasLArnold,JeffreyACohen,AlasdairJColes,DAlastairSCompston,ChristianConfavreux*,EdwardFox,Hans-PeterHartung,EvaHavrdova,TamaraMiller,KrzysztofWSelmaj,CaryLTwyman,andHowardWeiner.Genzyme:AjiNair;LindaKasten.CARE-MSIIwassponsoredbyGenzyme,aSanoficompany,andBayerHealthcarePharmaceuticals.EditorialsupportforthisposterwasprovidedbyRichardHogan,EvidenceScientificSolutions,andwasfundedbyGenzyme.G.G.reportsreceivingcompensationforconsulting,servingonascientificadvisoryboard,speaking,orotheractivitiesfromBiogen-Idec,FivePrimeTherapeutics,Genzyme,GWPharma,Merck-Serono,Novartis,Roche,Synthon,Teva,andVertexPharmaceuticals.G.G.receivedcompensationforservingasajournaleditorforMultiple Sclerosis and Related DisordersandresearchsupportfromSerono.D.H.MandJ.P.reportreceivingpersonalcompensationasemployeesofGenzyme.J.H.reportsreceivingpersonalcompensationforconsulting,servingonascientificadvisoryboard,speaking,orotheractivitiesfromBiogenIdec.AlemtuzumabisapprovedinAustralia,theEuropeanUnion,andMexicofortreatmentofactiveRRMSdefinedbyclinicalorimagingfeatures,inBrazilfortreatmentofrelapsingformsofMS,andinCanadaforpatientswithinadequateresponsetointerferonbetaorotherDMTs.Rebif®isaregisteredtrademarkofEMDSerono,Inc.*Deceased.

Sustained Improvement in Disability Outcomes with Alemtuzumab in Active Relapsing-Remitting Multiple Sclerosis Patients Who Participated in CARE-MS II: Three-Year Follow-up

G Giovannoni,1DHMargolin,2 J Palmer,2 J Herbert3

1QueenMaryUniversityofLondon,BartsandTheLondonSchoolofMedicine,London,UK;2Genzyme,aSanoficompany,Cambridge,MA,USA;3NewYorkUniversityMedicalCenter,NewYork,NY,USA

Presented at the 66th Annual Meeting of the American Academy of Neurology (AAN), April 26–May 03, 2014, Philadelphia, PA

P3.165

Figure 2. Mean EDSS Change: Proportion Improved, Remained Stable, or Worsened in Patients Who Had Received Alemtuzumab 12 mg in the Core Study

• AtYear3,66%ofalemtuzumab-treatedpatientshadeitherstableorimprovedEDSSscores from extension study baseline (data not shown)

• AmongpatientswhoseEDSSscoreremainedstablefrombaselinetoYear2,75%eithercontinuedtoremainstableorexperiencedimprovementfromYears2–3(Figure 3)

• AmongpatientswhoseEDSSscoreimprovedfrombaselinetoYear2,58%remainedstableorimprovedfurtherfromYears2–3(Figure 3)

Sustained Reduction in Preexisting Disability• AtYear3,morethanonethirdofpatientswhohadreceivedalemtuzumab12mginthecorestudyattainedimprovementinpreexistingdisabilitysustainedfor6months,asmeasured by 6-month sustained reduction in disability (Figure 4) – Aboutonequarterofthepatientsachieved12-monthsustainedreductionindisability

at Year 3

Durability of Effect • MeanEDSSscoreatYear3was2.5forpatientswhoreceived2coursesofalemtuzumab

over 3 years – Year3meanEDSSscorechangefromcorestudybaselinewas−0.16inthispatientsubgroup

• AtYear3,EDSSscorewasimprovedfromcorestudybaselinein48%ofpatientswhoreceived2coursesofalemtuzumabover3yearsandstableinafurther28%ofpatients(data not shown)

• AmongpatientswhoseEDSSscoreremainedstablefrombaselinetoYear2,79%eithercontinuedtoremainstableorexperiencedimprovementfromYears2–3(Figure 5)

• AmongpatientswhoseEDSSscoreimprovedfrombaselinetoYear2,61%remainedstableorimprovedfurtherfromYears2–3(Figure 5)

Sustained Reduction in Preexisting Disability• Forpatientswhoreceivedonly2coursesofalemtuzumabover3years,theproportionsachieving3-,6-,and12-monthsustainedreductionindisabilitywere45%,37%,and28% at Year 3 (data not shown)

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;EDSS=ExpandedDisabilityStatusScale.

EDSS=ExpandedDisabilityStatusScale

Figure 1. EDSS Score over Time in the Core Study and Extension

0 6 12 18 24 30 363 9 15 21 27 33

426 419 422 410 416 373 370419 419 415 413 367 364

0

2.00

2.40

2.60

2.20

2.80Baseline EDSS

3.00

Follow-up MonthNo. of Patients

EDSS

Sco

re

Alemtuzumab 12 mg

CARE-MS II Core Study Extension

(N=423)Years 0–2

(N=369)Years 0–3

Prop

ortio

n of

Pat

ient

s (%

)

60 Improved

Remained stable

Worsened50

40

30

20

10

0

46

302524

30

45

(N=178)

ImprovedYears 0–2

EDSS Shift Category (Baseline through Year 2)(N=112)

Remained stableYears 0–2

Prop

ortio

n of

Pat

ient

sat

Yea

r 3 (%

) 60

70

80 Improved from Year 2 to Year 3

Remained Stable from Year 2 to Year 3

50

40

30

20

10

011.8

46.651.8

23.2

Figure 3. EDSS Improvement from Year 2 to Year 3 in Alemtuzumab-treated Patients Who Improved or Remained Stable from Baseline to Year 2

EDSS=ExpandedDisabilityStatusScale

35%

43%

0 6 12 18 24 30 360

10

20

30

40

50

Follow-up Month

CARE-MS II Core Study Extension

321 280 241 222 200 172 1623-Month SRD

Prop

ortio

n of

Pat

ient

s w

ith S

usta

ined

R

educ

tion

in D

isab

ility

(%)

29%35%

321 290 262 245 221 190 1826-Month SRD

22%27%

321 294 275 263 245 215 20712-Month SRD

No. at Risk

Figure 4. Percentage of Patients with 3-, 6-, and 12-Month Sustained Reduction in Disability

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;SRD=sustainedreductionindisability

Figure 5. EDSS Improvement from Year 2 to Year 3 in Patients Treated with 2 Courses of Alemtuzumab over 3 Years Who Improved or Remained Stable from Baseline to Year 2

EDSS=ExpandedDisabilityStatusScale

(N=148)

ImprovedYears 0–2

EDSS Shift Category (Baseline through Year 2)(N=96)

Remained stableYears 0–2

Prop

ortio

n of

Pat

ient

sat

Yea

r 3 (%

) 60

70

80 Improved from Year 2 to Year 3

Remained Stable from Year 2 to Year 3

50

40

30

20

10

012.2

48.654.2

25.0

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;EDSS=ExpandedDisabilityStatusScale

REFERENCES1. Hu Y, et al. Immunology 2009;128:260-70. 2. Weber MS, Hemmer B. Results Probl Cell Differ 2010;51:115-26. 3. Havari E, et al. Immunology 2014;141:123-31. 4. Cox AL, et al. Eur J Immunol 2005;35:3332-42. 5. Coles AJ, et al. N Engl J Med 2008;359:1786-801. 6. Cohen JA, et al. Lancet 2012;380:1819-28. 7. Coles AJ, et al. Lancet 2012;380:1829-39. 8. Graves J, et al. Neurology 2013;30 (abstract P3.158). 9. Fox EJ, et al. Neurology 2013;30 (abstract S41.001).

CONCLUSIONS• Interim data from the CARE-MS II extension study demonstrate that alemtuzumabhasdurableefficacyondisabilitythrough3yearsinpatientswhohadrelapsedonpriortherapy,despitethemajorityofpatientsreceivingnoadditionalalemtuzumabtreatmentcoursesorotherDMTs – AlmosthalfofalemtuzumabpatientsdemonstratedimproveddisabilityscoresatYear3comparedwiththatatstudybaseline

– Morethanonethirdofformeralemtuzumabpatientsattainedsustaineddisabilityimprovement(6-monthsustainedreductionindisability) by Year 3

– Similardisabilityoutcomeswereobservedinpatientswhoreceivedonly 2 treatment courses over 3 years

• Thesefindings,togetherwithpreviouslyreporteddata,supportthepositivebenefit-riskprofileforalemtuzumabasapotentialtreatmentforRRMSinpatientswhorelapsedonpriortherapy

INTRODUCTION• AlemtuzumabisahumanizedmonoclonalantibodyapprovedinAustralia,Brazil,Canada,theEuropeanUnion,andMexicoforthetreatmentofactiverelapsing-remittingmultiplesclerosis(RRMS)thatselectivelytargetsCD52,resultingindepletionandsubsequentrepopulationofcirculatingTandBlymphocytes1-4

• Alemtuzumab,administeredin2annualcourses,hasdemonstratedsuperiorefficacyvs.high-dosesubcutaneousinterferonbeta-1a(SCIFNB-1a)intreatment-naiveRRMSpatients(CAMMS223[NCT00050778];ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis[CARE-MS]I[NCT00530348])5,6;andinpatientswhorelapsedonapriortherapy(CARE-MSII[NCT00548405])7 – Intheseclinicaltrials,alemtuzumabhadaconsistentandmanageablesafetyprofile,withthemostcommonadverseevents(AEs)beinginfusion-associatedreactions,non-serious infections, and autoimmune AEs

• InCARE-MSII,alemtuzumabsignificantlyreduced6-monthsustainedaccumulationofdisabilityat2yearsby49%beyondthatwithSCIFNB-1a(p<0.0001),andalemtuzumabpatientsweremorethantwiceaslikelytodemonstrate6-monthsustainedimprovementinpreexistingdisability(hazardratio2.57;p=0.0002)7 – PatientstreatedwithalemtuzumabalsohadsignificantlyimprovedvisualoutcomesusingSloanlow-contrastacuitymetrics,andfunctionaloutcomesusingMultipleSclerosisFunctionalComposite,comparedwithSCIFNB-1aatYear2(p<0.05)7,8

OBJECTIVE• ThepresentstudyexaminedthedurabilityofdisabilityimprovementinYear3follow-upduringanongoingextensionstudy(NCT00930553)ofalemtuzumabpatientswhorelapsedonapriortherapy

METHODSStudy DesignCore Study7

• CARE-MSIIwasarandomized,rater-blinded,active-controlled,head-to-head,phase3trial of 24 months’ duration

• Entrycriteriaincludedage18–55years,baselineExpandedDisabilityStatusScale(EDSS)score ≤5,MSsymptomonsetwithin10years,activeRRMS(≥2relapsesinprior2yearsand ≥1intheprioryear),andrelapseonpriortherapy(≥1relapseduringtreatmentwithIFNBorglatirameracetate,afterreceivingthattherapyfor≥6months[priortreatmentwithothertherapieswasalsopermitted])

• Patientswererandomized2:1toreceivealemtuzumab12mg/dayviaintravenous(IV)infusions on 5 consecutive days at baseline and on 3 consecutive days 12 months later, or SCIFNB-1a44µg3timesweekly

Extension Study9

• Patients who had received alemtuzumab in the core study received re-treatment as neededintheextension(12mg/dayIVon3consecutivedays) – Re-treatmentcriteriawereoneofthefollowing,basedontheinvestigator’sclinical

decision: ■ ≥1protocol-definedrelapse ■ ≥2neworenlargingT2and/orgadolinium-enhancingbrainorspinallesionsonmagneticresonanceimaging

– Useofotherdisease-modifyingtherapies(DMTs)wasallowedbasedoninvestigators’clinical decisions

– AlldatapresentedherearefrompatientswhoreceivedalemtuzumabinthecoreCARE-MS II study

Disability Assessment• EDSSwasassessedbyblindedratersatcorestudybaselineandevery3months• Disabilityoutcomes

– ChangefromcorestudybaselineonEDSS – Proportionofpatientsimproved,remainedstable,orworsenedonEDSS

■ Improvementandworseningweredefinedas≥0.5-pointdecreaseorincrease,respectively,fromcorestudybaselineEDSSscore

– Sustained reduction in disability: decrease from core study baseline by ≥1EDSSpointconfirmedover3,6,or12monthsforpatientswithbaselineEDSSscores≥2.0

Statistical Analysis• AnalyseswerebasedonYear3follow-updataonpatientswhohadreceivedalemtuzumab12mginthecoreCARE-MSIIstudy

• DatafromCARE-MSIIpatientswhotransitionedintotheextensionstudywereanalyzedfromthetimeoffirsttreatment

• Kaplan-Meieranalysisoftimeto3-,6-,and12-monthsustainedreductionindisability• Analyseswereundertakenforallpatientsintheextensionandforpatientswhoreceived

only 2 courses over 3 years

RESULTSPatients• Morethan90%(393of423)ofpatientswhohadreceivedalemtuzumab12mginCARE-MSIIandcompletedthecorestudyenteredtheextension

• Approximately80%didnotreceivere-treatmentduringYear3• Fewerthan3%offormeralemtuzumab-treatedpatientsreceivedanotherDMTinYear3Disability Improvement • MeanEDSSscoreswere2.7atcorestudybaseline,2.5atYear2,and2.6atYear3(Figure 1)

• MeanEDSSscoresremainedbelowpre-treatmentvaluesduringthethirdyear – Year2meanEDSSscorechangefromcorestudybaseline:−0.21 – Year3meanEDSSscorechangefromcorestudybaseline:−0.06

• AtYear3,70%ofalemtuzumab-treatedpatientshadeitherstableorimprovedEDSSscores from core study baseline (Figure 2),similartotheresultsseenoverYears0–2

Acknowledgments and DisclosuresCARE-MSIIsteeringcommittee:DouglasLArnold,JeffreyACohen,AlasdairJColes,DAlastairSCompston,ChristianConfavreux*,EdwardFox,Hans-PeterHartung,EvaHavrdova,TamaraMiller,KrzysztofWSelmaj,CaryLTwyman,andHowardWeiner.Genzyme:AjiNair;LindaKasten.CARE-MSIIwassponsoredbyGenzyme,aSanoficompany,andBayerHealthcarePharmaceuticals.EditorialsupportforthisposterwasprovidedbyRichardHogan,EvidenceScientificSolutions,andwasfundedbyGenzyme.G.G.reportsreceivingcompensationforconsulting,servingonascientificadvisoryboard,speaking,orotheractivitiesfromBiogen-Idec,FivePrimeTherapeutics,Genzyme,GWPharma,Merck-Serono,Novartis,Roche,Synthon,Teva,andVertexPharmaceuticals.G.G.receivedcompensationforservingasajournaleditorforMultiple Sclerosis and Related DisordersandresearchsupportfromSerono.D.H.MandJ.P.reportreceivingpersonalcompensationasemployeesofGenzyme.J.H.reportsreceivingpersonalcompensationforconsulting,servingonascientificadvisoryboard,speaking,orotheractivitiesfromBiogenIdec.AlemtuzumabisapprovedinAustralia,theEuropeanUnion,andMexicofortreatmentofactiveRRMSdefinedbyclinicalorimagingfeatures,inBrazilfortreatmentofrelapsingformsofMS,andinCanadaforpatientswithinadequateresponsetointerferonbetaorotherDMTs.Rebif®isaregisteredtrademarkofEMDSerono,Inc.*Deceased.

Sustained Improvement in Disability Outcomes with Alemtuzumab in Active Relapsing-Remitting Multiple Sclerosis Patients Who Participated in CARE-MS II: Three-Year Follow-up

G Giovannoni,1DHMargolin,2 J Palmer,2 J Herbert3

1QueenMaryUniversityofLondon,BartsandTheLondonSchoolofMedicine,London,UK;2Genzyme,aSanoficompany,Cambridge,MA,USA;3NewYorkUniversityMedicalCenter,NewYork,NY,USA

Presented at the 66th Annual Meeting of the American Academy of Neurology (AAN), April 26–May 03, 2014, Philadelphia, PA

P3.165

Figure 2. Mean EDSS Change: Proportion Improved, Remained Stable, or Worsened in Patients Who Had Received Alemtuzumab 12 mg in the Core Study

• AtYear3,66%ofalemtuzumab-treatedpatientshadeitherstableorimprovedEDSSscores from extension study baseline (data not shown)

• AmongpatientswhoseEDSSscoreremainedstablefrombaselinetoYear2,75%eithercontinuedtoremainstableorexperiencedimprovementfromYears2–3(Figure 3)

• AmongpatientswhoseEDSSscoreimprovedfrombaselinetoYear2,58%remainedstableorimprovedfurtherfromYears2–3(Figure 3)

Sustained Reduction in Preexisting Disability• AtYear3,morethanonethirdofpatientswhohadreceivedalemtuzumab12mginthecorestudyattainedimprovementinpreexistingdisabilitysustainedfor6months,asmeasured by 6-month sustained reduction in disability (Figure 4) – Aboutonequarterofthepatientsachieved12-monthsustainedreductionindisability

at Year 3

Durability of Effect • MeanEDSSscoreatYear3was2.5forpatientswhoreceived2coursesofalemtuzumab

over 3 years – Year3meanEDSSscorechangefromcorestudybaselinewas−0.16inthispatientsubgroup

• AtYear3,EDSSscorewasimprovedfromcorestudybaselinein48%ofpatientswhoreceived2coursesofalemtuzumabover3yearsandstableinafurther28%ofpatients(data not shown)

• AmongpatientswhoseEDSSscoreremainedstablefrombaselinetoYear2,79%eithercontinuedtoremainstableorexperiencedimprovementfromYears2–3(Figure 5)

• AmongpatientswhoseEDSSscoreimprovedfrombaselinetoYear2,61%remainedstableorimprovedfurtherfromYears2–3(Figure 5)

Sustained Reduction in Preexisting Disability• Forpatientswhoreceivedonly2coursesofalemtuzumabover3years,theproportionsachieving3-,6-,and12-monthsustainedreductionindisabilitywere45%,37%,and28% at Year 3 (data not shown)

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;EDSS=ExpandedDisabilityStatusScale.

EDSS=ExpandedDisabilityStatusScale

Figure 1. EDSS Score over Time in the Core Study and Extension

0 6 12 18 24 30 363 9 15 21 27 33

426 419 422 410 416 373 370419 419 415 413 367 364

0

2.00

2.40

2.60

2.20

2.80Baseline EDSS

3.00

Follow-up MonthNo. of Patients

EDSS

Sco

re

Alemtuzumab 12 mg

CARE-MS II Core Study Extension

(N=423)Years 0–2

(N=369)Years 0–3

Prop

ortio

n of

Pat

ient

s (%

)

60 Improved

Remained stable

Worsened50

40

30

20

10

0

46

302524

30

45

(N=178)

ImprovedYears 0–2

EDSS Shift Category (Baseline through Year 2)(N=112)

Remained stableYears 0–2

Prop

ortio

n of

Pat

ient

sat

Yea

r 3 (%

) 60

70

80 Improved from Year 2 to Year 3

Remained Stable from Year 2 to Year 3

50

40

30

20

10

011.8

46.651.8

23.2

Figure 3. EDSS Improvement from Year 2 to Year 3 in Alemtuzumab-treated Patients Who Improved or Remained Stable from Baseline to Year 2

EDSS=ExpandedDisabilityStatusScale

35%

43%

0 6 12 18 24 30 360

10

20

30

40

50

Follow-up Month

CARE-MS II Core Study Extension

321 280 241 222 200 172 1623-Month SRD

Prop

ortio

n of

Pat

ient

s w

ith S

usta

ined

R

educ

tion

in D

isab

ility

(%)

29%35%

321 290 262 245 221 190 1826-Month SRD

22%27%

321 294 275 263 245 215 20712-Month SRD

No. at Risk

Figure 4. Percentage of Patients with 3-, 6-, and 12-Month Sustained Reduction in Disability

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;SRD=sustainedreductionindisability

Figure 5. EDSS Improvement from Year 2 to Year 3 in Patients Treated with 2 Courses of Alemtuzumab over 3 Years Who Improved or Remained Stable from Baseline to Year 2

EDSS=ExpandedDisabilityStatusScale

(N=148)

ImprovedYears 0–2

EDSS Shift Category (Baseline through Year 2)(N=96)

Remained stableYears 0–2

Prop

ortio

n of

Pat

ient

sat

Yea

r 3 (%

) 60

70

80 Improved from Year 2 to Year 3

Remained Stable from Year 2 to Year 3

50

40

30

20

10

012.2

48.654.2

25.0

CARE-MS=ComparisonofAlemtuzumabandRebif®EfficacyinMultipleSclerosis;EDSS=ExpandedDisabilityStatusScale