REUNIÃO DO OUTONO - APECS · REUNIÃO DO OUTONO 17 de novembro de 2018 Highlights from Glasgow ....

1.   Amber:week96results2.   GS-US-380-1490Study

3.   BRIGHTEStudy:week48safetyandefficacyresults4.   LATTE-2Week160Results5.   SafetyandefficacyofDoravirine/Lamivudine/TDF6.   EfficacyofMK-8591

REUNIÃO DO OUTONO 17denovembrode2018

Highlights from Glasgow

PhaseIIIRandomized,ControlledClinicalTrialofBictegravirCoformulatedwithFTC/TAFinaFixed-doseCombination(B/F/TAF)versus

Dolutegravir(DTG)+F/TAFinTreatment-naïveHIV-1PositiveAdults:Week96

HansJürgenStellbrink,1JoseArribas,2JeffreyL.Stephens,3HelmutAlbrecht,4PaulE.Sax,5FrancoMaggiolo,6CatherineCreticos,7ClaudiaT.Martorell,8XuelianWei,9KirstenWhite,9

SeanE.Collins,9AndrewCheng,9HalMartin91ICHStudyCenter,Hamburg,Germany;2HospitalUniversitarioLaPaz,Madrid,Spain;3MercerUniversitySchoolofMedicine,Macon,GA,US;

4PalmettoHealth,Richland,SC,US;5BrighamandWomen’sHospital,Boston,MA,US;6AziendaOspedalieraPapaGiovanniXXIII,Bergamo,Italy;7HowardBrownHealthCenter,Chicago,IL.US;8InfectiousDiseasesandTheResearchInstitute,Springfield,MA,US;9GileadSciences,Inc.,FosterCity,

CA

HIVGlasgow,Abstract418596028–31October2018

Glasgow,UK

Introduction

•  Bictegravir,anovel,potentINSTIwithahighbarriertoresistance,wascoformulatedwithemtricitabineandtenofoviralafenamideintoasingle-tabletregimen(B/F/TAF)andisapprovedintheUS,Europe,Australia,andCanadaasBiktarvy®

•  Unboosted,oncedailydosingwithoutregardtofood•  B/F/TAFhasshownnoninferiorityatWeek48tocurrentstandard-of-carecomparators,withnotreatment-emergentresistance,andwaswelltoleratedacrossfiverandomized,phase3studiesinadultslivingwithHIV-1,includingastudyof470women1-5

•  AstudycomparingB/F/TAFtocoformulateddolutegravir(DTG),abacavir,andlamivudine,showednoninferiorefficacy,changesinbonemineraldensityandrenalmarkerswerecomparablebetweenarms,andtherewerenocasesofrenaltubulopathythrough96weeks6

13

1.  Saxetal.Lancet2017;390:2073-82. 2.  Gallantetal.Lancet2017;390:2063-72.3.  Molinaetal.LancetHIV2018;5:e357-65.4.  Daaretal.LancetHIV2018;5:e347-56.5.  Kityoetal.CROI2018;March3-7,Boston,abstr#500.6.  Wohletal.PresentedatIDWeek2018;October3-7,abstr#74246.

GS-US-380-1490 Study Design

•  Phase3,randomized,double-blind,active-controlledstudy•  StratifiedbyHIV-1RNA,CD4cellcount,geographicregion(USAvsnon-USA)•  NorthAmerica,Europe,Australia,andLatinAmerica•  ChronichepatitisBand/orCvirus(HBV/HCV)infectionallowed

•  Primaryendpoint:proportionwithHIV-1RNA<50copies/mLatWeek48•  B/F/TAF89.4%vsDTG+F/TAF92.9%withHIV-1RNA<50c/mL(p=0.12)1

•  Secondaryendpoint:proportionwithHIV-1RNA<50copies/mLatWeek96•  Noninferioritymarginof12%basedonFDASnapshotalgorithm

14 ClinicalTrials.govNCT02607956.c,copies;eGFRCG,estimatedglomerularfiltrationratebyCockcroft-Gaultequation.1.Saxetal.Lancet2017;390:2073-82.

48 Week 0 144

Treatment-NaïveAdults§  HIV-1RNA≥500c/mL

§  eGFRCG≥30mL/min

n=320

n=325

1°Endpoint

96

DTG+F/TAFPlaceboQD

B/F/TAFQD

B/F/TAFPlaceboQD

DTG+F/TAFQD

1:1

2ºEndpoint

Participant Disposition From Baseline to Week 96

15 *Losttofollow-up(n=3),withdrewconsent(n=14),investigator’sdiscretion(n=2),AE(n=1),outsideofvisitwindow(n=2),other(n=3).

Randomized,n=657

Screened,n=742 Screenfailures,n=60

Meteligibilitycriteriabutnotrandomized,n=25*

B/F/TAFn=320

DTG+F/TAFn=325

Stillontreatmentn=272

Stillontreatmentn=289

Randomizedandnottreated,n=7

48 (15%) Reason for D/C, n 36 (11%) 14 Patient decision 12 14 Lost to follow-up 7 6 AE 5 6 Investigator discretion 2 4 Pregnancy 3 2 Death 3 2 Protocol violation 1 0 Noncompliance 3 0 Lack of efficacy 0

Randomizedandtreated

Randomizedandnottreated,n=5

Virologic Outcome at Week 96 Snapshot analysis

•  AtWeek96,B/F/TAFwasnoninferiortoDTG+F/TAFbyFDASnapshotanalysis•  Perprotocolanalysis: B/F/TAF100%vsDTG+F/TAF98%

•  MeanCD4increasefrombaselineatWeek96:•  B/F/TAF+237cells/µLvsDTG+F/TAF+281cells/µL(p=0.008)•  MeanCD4%change B/F/TAF11%vsDTG+F/TAF11%(p=0.37)•  MeanabsoluteCD4 B/F/TAF693vsDTG+F/TAF733(p=0.13)

16

%TreatmentDifference(95%CI)

-7.9 3.2-2.3

-12 120-6 6

FavorsDTG+F/TAF

FavorsB/F/TAF

84

412

86

311

0

20

40

60

80

100

HIV-1 RNA <50 copies/mL

HIV-1 RNA ≥50 copies/mL

No Virologic Data

DTG + F/TAF (n=325)

B/F/TAF (n=320)

Pro

porti

on o

f par

ticip

ants

, %

Virologic Outcome

P-value was from analysis of variance (ANOVA) model adjusted by the baseline HIV-1 RNA and region stratum.

269 320

281 325

14 320

9 325

35 325

37 320

Resistance Analysis Population through Week 96

17

B/F/TAF n=320

DTG + F/TAF n=325

Resistance analysis population 7 6

Emergent resistance 0 0

§  Noparticipantdevelopedtreatment-emergentresistancethroughWeek96

§  ResistanceanalysispopulationincludesanyparticipantwithvirologicreboundatorafterWeek8–  Confirmedvirologicfailurewithoutresuppression

§  TwoconsecutiveHIV-1RNAtests≥50c/mLafterachieving<50c/mlandHIV-1RNA≥200c/mLattheconfirmationtestor

§  ≥1log10copies/mLincreaseinHIV-1RNAfromnadir–  HIV-1RNA≥200c/mLatWeek96orlastvisitonstudydrug(didnotrequireconfirmation)

§  Thesecond,confirmatorysamplewassentforresistanceanalysis,unlesstherewasnofollow-upsample

17 19

4 6

16 16

5 6

0

10

20

30

40

Fasting Lipid Changes at Week 96

•  Similarpercentagesofparticipants:•  Wereonlipid-loweringagentsatbaseline:B/F/TAF6.6%,DTG+F/TAF5.5%,p=0.62•  Initiatedlipid-loweringagentsduringthestudy:B/F/TAF3.4%,DTG/ABC/3TC3.7%,p=1.00

P-valueswerefromthe2-sidedWilcoxonranksumtesttocomparethe2treatmentgroups.

Baseline,mg/dL 156 161 98 99 43 43 97 95

FastingLipidComponentTotal Cholesterol

p=0.51 LDL Cholesterol

p=0.24 Triglycerides

p=0.79 HDL Cholesterol

p=0.23

Med

ian

Cha

nge

From

B

asel

ine,

mg/

dL

B/F/TAF DTG + F/TAF

0

-0.1

-1

-0.5

0

0.5

1

3.7 3.7

Med

ian

Cha

nge

From

B

asel

ine

Total Cholesterol:HDL p=0.14

18

Conclusions •  InitialHIV-1therapywithB/F/TAFwasnoninferiortoDTG+F/TAFatWeek96bySnapshotalgorithmwithhighratesofvirologicsuppression(HIV-1RNA<50copies/mL)

•  84%B/F/TAFvs86%DTG+F/TAF•  Sensitivityanalysesconfirmednoninferiority

•  Per-protocol:100%B/F/TAFvs98%DTG+F/TAF

•  Notreatment-emergentresistance

•  B/F/TAFwaswelltolerated•  FewAEsleadingtodiscontinuationoccurred(6vs5intheDTG+F/TAFarm)•  Moretreatment-relatedAEswerereportedintheDTG+F/TAFarm(p=0.02)

•  TherewerenodiscontinuationsduetorenalAEsandnocasesoftubulopathy,includingFanconisyndrome,ineithertreatmentgroup

•  Changesfrombaselineinlipidparameterswereequivalent

•  Theseresultsprovidefurtherevidenceoflonger-termsafety,efficacy,andhighbarriertoresistanceofB/F/TAFinpeoplelivingwithHIV-1

19

1IcahnSchoolofMedicineatMountSinai,NewYork,NY,USA;2HôpitalSaint-Louis,APHPandUniversityofParisDiderotParis,InfectiousDiseases,Paris,France;3YaleUniversitySchoolofMedicine,NewHaven,CT,USA;4FundaciónHuesped,BuenosAires,Argentina;5QuestClinicalResearch,SanFrancisco,CA,USA;6AIDSResearchConsortiumofAtlanta,GA,USA;7TheInstitutoNacionaldeInfectologiaEvandroChagas,FundaçãoOswaldoCruz,RiodeJaneiro,Brazil;8ClinicofInfectiousDiseases,Vita-SaluteSanRaffaeleUniversity,Milan,Italy;9HôpitalTenon,Paris,France;10GlaxoSmithKline,UpperProvidence,Philadelphia,PA,USA;11ViiVHealthcare,ResearchTrianglePark,NC,USA;12ViiVHealthcare,Branford,CT,USA

Week 48 Safety and Efficacy of the HIV-1 Attachment Inhibitor Prodrug Fostemsavir in Heavily Treatment-Experienced Participants (BRIGHTE Study)

J Aberg,1 J-M Molina,2 M Kozal,3 P Cahn,4 J Lalezari,5 M Thompson,6 R Diaz,7 A Castagna,8 G Pialoux,9 M Gummel,10 A Pierce,11 P Ackerman,12 C Llamoso,12 M Lataillade12

•  Fostemsavir (FTR) is a first-in-class attachment inhibitor prodrug1 that is being specifically developed for HIV-1-infected, heavily treatment-experienced (HTE) patients

•  FTR has a unique resistance profile with no in vitro cross-resistance to other classes of ARVs2,3

•  AttheWeek24interimanalysisfortheongoingPhase3BRIGHTEstudy,FTRdemonstrated4

•  Superiorefficacyrelativetoplacebo(0.8log10c/mLdecreaseforFTRvs0.2log10c/mLforplacebo;treatmentdifference=0.625,P<0.0001)after8daysoffunctionalmonotherapy(primaryendpoint)

•  AmediandecreaseinHIV-1RNAof1log10c/mLinparticipantswithbaselineHIV-1RNA>1,000c/mLintheRandomisedCohortatDay8

•  Virologicsuppression(HIV-1RNA<40c/mL)in53%ofparticipantsintheRandomisedCohortand37%intheNon-randomisedCohort(81%ofwhomhadFTRastheonlyfullyactiveARV)atWeek24

•  AmeanincreaseinCD4+Tcellcountby90cells/µLfrombaselineatWeek24intheRandomizedCohort

•  Agenerallywell-toleratedsafetyprofilewithfewAEsleadingtodiscontinuation

•  HerewepresentWeek48efficacyandsafetyresultsfromtheongoingBRIGHTEstudy(formerly205888/AI438-047)

Overview of Fostemsavir

Abergetal.HIVGlasgow2018;Glasgow,UK.Oral334A.

AE,adverseevent;ARV,antiretroviral.

1.Brownetal.JPharmSci.2013;102:1742-1751.2.Nowicka-Sansetal.AntimicrobAgentsChemother.2012;56:3498-3507.3.Lietal.AntimicrobAgentsChemother.2013;57:4172-4180.4.Kozaletal.Presentedat:EACS2017.OralPS8/5.

Conversionoffostemsavirtotemsavir1

Temsavir (active moiety)

Fostemsavir (prodrug)

Alkaline phosphatase

Gastrointestinal lumen

Blood plasma

Temsavir

Study Design

RandomisedCohort§:HTEparticipantsfailingcurrentregimenwithconfirmedHIV-1RNA≥400c/mLand:•  1or2ARVclassesremaining&≥1

fullyactive&availableagentperclass

•  Unabletoconstructviableregimenfromremainingagents

Day 1

Blindedplacebo+failingregimen

BlindedFTR600mgBID+failingregimenRandomised

3:1

Day 8 – Primary Endpoint

Non-randomisedCohort§:HTEparticipants,failingcurrentregimenwithconfirmedHIV-1RNA≥400c/mLand:•  0ARVclassesremainingandno

remainingfullyactiveapprovedagents‡

Non-randomised OpenLabelFTR600mgBID+OBT

Day 1

Week 24 Week 48 Week 96 End of Study†

Day 9 – Open Label FTR + OBT

Week 24* Week 48* Week 96* End of Study†

OpenLabelFTR600mgBID+OBT


*MeasuredfromthestartofopenlabelFTR600mgBID+OBT;†Thestudyisexpectedtobeconducteduntilanadditionaloption,

rolloverstudyormarketingapproval,isinplace;‡UseofinvestigationalagentsaspartofOBTwaspermitted;§TherewasnoscreeningTMRIC50criteria.

BID,twice-daily;IC50,halfmaximalinhibitoryconcentration;OBT,optimisedbackgroundtherapy.

BRIGHTEisanongoingPhase3randomised,placebo-controlled,doubleblindtrial

Prior ARV Exposure and Initial OBT


*15/19receivedinvestigationalARVIbalizumab.INI,integraseinhibitor;NRTI,nucleosidereversetranscriptaseinhibitors;NNRTI,non-NRTI;PI,proteaseinhibitor.

PriorExposuretoARVs FullyActiveandAvailableARVAgentsinInitialOBT

%ofP

articipan

ts

%ofP

articipan

ts

6

81

50

[VALOR]*

43

0 0 0 0

10 20 30 40 50 60 70 80 90

100

Randomised Cohort (N=272)

Non-randomised Cohort (N=99)

ARV Agents = 0 ARV Agents = 1 ARV Agents = 2 ARV Agents > 2

99 92 94

75

26

39

100 96 99 95

40

69

0

20

40

60

80

100

NRTI NNRTI PI INI CCR5 Antagonist

Fusion Inhibitor

Randomised Cohort (N=272)

Non-randomised Cohort (N=99)

•  Overall,71%(262/371)ofparticipantsweretreatedforHIV-1infectionfor>15years,85%(316/371)hadpriorexperiencewith≥5ARVregimens(80%and96%wereINSTIandPIexperienced,respectively),and86%(320/371)hadahistoryofAIDS

•  IntheRandomisedCohort,50%(137/272)and43%had1or2FAAsintheirinitialOBT,respectively•  Ofthe99Non-randomizedparticipants,81hadnoapprovedFAAsorinvestigationalARVsintheirinitialOBTand

15hadinvestigationalibalizumabintheirinitialOBT

Study Disposition Through Week 48


ScreenedN=731

RandomisedCohortN=272

ScreeningFailuresN=360

Ongoingn=215(79%)

Withdrawn*n=57†(21%)

Non-randomisedCohortN=99

Ongoingn=67(68%)

Withdrawnn=32‡(32%)

*6participants(FTRn=5;placebon=1)discontinuedduringthedouble-blindperiodofthestudy.†Withdrawalreasons(n,%):AEs(9,3%),lackofefficacy(12,4%),non-adherence(11,4%),withdrawnconsent(5,2%),losttofollow-up(7,3%),nolongermetstudycriteria(3,1%),death(8,3%),pregnancy(1,<1%)andother(1,<1%).§Withdrawalreasons(n,%):AEs(5,5%),lackofefficacy(6,6%),non-adherence(5,5%),withdrawnconsent(1,1%),losttofollow-up(1,1%),nolongermetstudycriteria(2,2%)anddeath(12,12%).

•  ThroughWeek48,57/272(21%,Randomised)and32/99(32%,Non-randomised)participantsdiscontinuedearly;sixparticipants(FTRn=5;placebon=1)discontinuedduringthedouble-blindperiod.

AtWeek24,53%ofRandomisedparticipantsand37%ofNon-randomisedparticipantshadanHIV-1RNA<40c/mL

<200 c/mL 69% (n=187)

<200 c/mL 43% (n=43)

<400 c/mL 70% (n=191)

<400 c/mL 44% (n=44)

0 10 20 30 40 50 60 70 80 90

100 Randomised cohort

Non-randomised cohort

Virologic Response at Week 48 (Snapshot Analysis)*


*ChangeinOBTforefficacyreasonswereconsideredvirologicfailuresinthisanalysis.

ART,antiretroviraltherapy;D/C,discontinued.

%ofP

articipan

ts

N = 272 N = 99

Mean Change in CD4+ T-cell Counts from Baseline through Week 48: Observed Analysis


SD,standarddeviation.

[VALOR] (n=249)

[VALOR] (n=247)

[VALOR] (n=234)

[VALOR] (n=228)

[VALOR] (n=90)

[VALOR] (n=87)

[VALOR] (n=83)

[VALOR] (n=83)

0

50

100

150

200

250

300

350

Baseline 12 24 36 48

Randomised Cohort Non-randomised Cohort

Mean CD4+ T-cell count at baseline was 153 cells/µL (SD=182) for the Randomised Cohort and 99 cells/µL (SD=131) for the Non-randomised Cohort

MeanCh

angeinCD4

+T-cellCo

untsfrom

Baseline

(cells/µL)+SD

WeeksonTherapy

Week 48 Safety Summary *

*Allsafetydatareflectcumulativeresultscollectedthroughthedatacutoffdateof4March2018.AlltreatedparticipantshadtheopportunitytocompletetheWeek72studyassessmentpriortothecurrentdatalock;†Themajority(15%)ofSAEswerefromtheinfections/infestationssystemorganclass;‡17/25 deaths were due to AIDS-related events, IRIS, or acute infection; estimated median CD4 T-cell count among participants who died was 7 cells/µL IRIS,immunereconstitutioninflammatorysyndrome;SAE, serious adverse event.

Parameter,n(%) RandomisedCohort(N=272)

Non-randomisedCohort(N=99)

TotalTreatedParticipants

(N=371)

AnyEvent 247(91) 96(97) 343(92)

Grade2-4relatedAes 55 (20) 22 (22) 77 (21)

Grade3-4AEs 70(26) 47(47) 117(32)

AEsleadingtoDiscontinuation 14(5) 13(13) 27(7)

SAEs† 85(31) 44(44) 129(35)

Related SAEs 7 (3) 3 (3) 10 (3)

Deaths‡ 11(4) 14(14) 25(7)


•  FTRwaswelltoleratedthroughWeek48withfewdiscontinuationsduetoAEs

•  92%(343/371)ofparticipantshad≥1AEs;mostwereGrade1to2inintensityandresolvedwithoutinterruptionofstudydrug

•  35%ofparticipantshad≥1seriousAE(SAE);mostwererelatedtoinfections

•  ComparedwiththeRandomisedCohort,theNon-randomizedCohortexperiencedhigherratesofSAEs(31%vs44%),Grade3to4AEs(26%vs47%)anddeaths(4%vs14%)

Grade 2 to 4 Treatment-Related AEs*


*Grade2–4relatedAEsoccurringin≥2%ofparticipantsineitherarm.

Parameter,n(%) RandomisedCohort(N=272)

Non-randomisedCohort(N=99)

TotalTreatedParticipants

(N=371)

AnyEvent 55 (20) 22 (22) 77 (21)

Nausea 10 (4) 5 (5) 15 (4)

Diarrhea 7 (3) 3 (3) 10 (3)

Headache 7 (3) 1 (1) 8 (2)

Immune reconstitution inflammatory syndrome 5 (2) 1 (1) 6 (2)

Vomiting 4 (1) 2 (2) 6 (2)

Fatigue 3 (1) 2 (2) 5 (1)

Asthenia 2 (<1) 2 (2) 4 (1)

•  ConsistentwiththeresultsfromWeek24,themostcommonGrade2to4treatment-relatedAEswerenausea(4%),diarrhea(3%)andheadache(2%)

•  RatesofvirologicsuppressionweremaintainedfromWeek24throughWeek48,despitecontinuedattritioninthisactivetrial

•  Therewerecontinued,clinicallymeaningful,improvementsinCD4+T-cellcountthroughWeek48,includingamongthosewhoweremostimmune-compromisedatbaseline

•  FTR-containingregimenswerewelltoleratedthroughWeek48withfewdiscontinuationsduetoAEs

•  Majorityofsignificantsafetyevents(Grade3-4AEs/SAEs/deaths)wererelatedtoinfectionsorprogressionofAIDSandoccurredinparticipantsintheNon-randomisedCohort,whohadlowerbaselineCD4countsandnoapprovedFAAstopairwithFTRatstudystart

•  Week48resultsfromtheongoingBRIGHTEstudysupportfurtherdevelopmentofFTRasatherapeuticoptionforHIV-1-infectedHTEparticipantswithmulti-drugresistanceandfewremainingactivetherapies

Conclusions


1ViiVHealthcare,ResearchTrianglePark,NC,USA;2HospitalLaPaz,Madrid,Spain;3ICHStudyCenter,Hamburg,Germany;4HôpitalBichatClaudeBernard,Paris,France;5GaryJ.Richmond,MD,PA,FortLauderdale,FL,USA;6MapleLeafResearch,Toronto,ON,Canada;7GlaxoSmithKline,Mississauga,ON,Canada;8GlaxoSmithKline,Collegeville,PA,USA;9JanssenResearchandDevelopment,Beerse,Belgium

Safety, Efficacy and Durability of Long-Acting Cabotegravir (CAB) and Rilpivirine (RPV) as Two-Drug IM Maintenance Therapy for HIV-1 Infection: LATTE-2 Week 160 Results

David A. Margolis,1 Juan Gonzalez Garcia,2 Hans-Jürgen Stellbrink,3 Yazdan Yazdanpanah,4 Gary Richmond,5 Graham Smith,6 Kenneth Sutton,1 David Dorey,7 Feifan Zhang,8 Kimberly Smith,1 Peter Williams,9 William Spreen1

•  LAinjectablesuspensionsofCABandRPVareinphaseIIIdevelopment

•  LATTE-2Week48/96datasupportedthedecisiontoevaluatetheQ4WandQ8WCABLA+RPVLAIMregimeninongoingphaseIIIstudies1

•  TheWeek160analysisevaluatedthelong-termefficacy,safety,andtolerabilityofbothIMdosingregimens

Introduction

Margolisetal.HIVGlasgow;Glasgow,UK.PosterP118.

CAB,cabotegravir;IM,intramuscular;LA,longacting;Q4W,every4wk;Q8W,every8wk;RPV,rilpivirine.

1.Margolisetal.Lancet.2017;390:1499-1510.

• PhaseIIb,multicenter,parallel-group,open-labelstudyinART-naiveHIV-infectedadults

LATTE-2 Study Design


ART,antiretroviraltherapy;CAB,cabotegravir;EP,extensionperiod;IM,intramuscular;LA,longacting;MP,maintenanceperiod;PO,oral;QD,oncedaily;Q4W,every4wk;Q8W,every8wk;RPV,rilpivirine.

•  309patientswereenrolled(ITT-exposed):91%male,20%non-white,and19%>100,000c/mLHIV-1RNA.286patientswererandomizedintotheMP;258completedMPwith252enteringEP

Snapshot Outcomes at Week 160


aDatapresentedfortherandomizedQ8W/Q4WIMarmsareinclusiveofMPandEP.DatapresentedfortheoptimizedQ8W/Q4WIMarmsareinclusiveofon-treatmenteventsoccurringfromthefirstdateoffirstinjectionintheEP,W100.b77c/mL.c>50c/mLatW96anddidnotqualifyforEP.dAddedinEP:CAD;MI(death);motorneurondisease.eRelocation;enteredLTFU;burdenoftravel;losttoFU.fAddedinEP:PD;losttoFU;WDbypatient.

Outcome at W160a Q8W IM

n (%) Q4W IM

n (%)

Optimized Q8W IM

n (%)

Optimized Q4W IM

n (%) Snapshot (ITT-ME) N=115 N=115 N=34 N=10 HIV-1 RNA <50 c/mL 104 (90) 95 (83) 33 (97) 10 (100) HIV-1 RNA ≥50 c/mL 5 (4) 0 1 (3) 0

Data in window not <50 c/mL 1 (<1)b 0 0 0 DC for lack of efficacy 1 (<1) 0 1 (3) 0 DC for other reason while not <50 c/mL

3 (3)c 0 0 0

No virologic data in window 6 (5) 20 (17) 0 0 W/D due to AE or death 1 (<1) 12 (10)d 0 0 W/D due to other reasons 5 (4)e 8 (7)f 0 0

•  Through160weeks,therewere2PDVFs,bothQ8W•  NoadditionalPDVFsoccurredafterWeek48inanyarm•  Resistancedatawerepreviouslyreported1

Protocol-Defined Virologic Failure


PDVF,protocol-definedvirologicfailure;Q8W,every8wk.

1.Margolisetal.Lancet.2017;390:1499-1510.

Adverse Events Through Week 160


aDatapresentedfortherandomizedQ8W/Q4WIMarmsareinclusiveofMPandEP.DatapresentedfortheoptimizedQ8W/Q4WIMarmsareinclusiveofon-treatmenteventsoccurringfromthefirstdateoffirstinjectionintheEP,W100.bMI(possiblydrug-related,fatal),epilepsy(fatal).cAddedinEP:Q8W:HepC;Q4W:CAD,MI,motorneurondisease,hypoesthesia/muscularweakness/fatigue;OptimizedQ4W:injectionsitepain.

Week 160 Safetya

Q8W IM N=115 n (%)

Q4W IM N=115 n (%)

Optimized Q8W IM

N=34 n (%)

Optimized Q4W IM

N=10 n (%)

Grade 3/4 AEs, excluding ISRs 24 (21) 29 (25) 0 1 (10) Drug-related grade 3/4 AEs, excluding ISRs

2 (2) 6 (5) 0 0

Serious AEs 17 (15) 21 (18) 2 (6) 0 Drug-related SAEs 0 1 (<1)b 0 0 Fatal SAEs 0 2 (2)b 0 0

AEs leading to withdrawalc 3 (3) 12 (10) 0 1 (10) Grade 3/4 hematology labs 4 (3) 2 (2) 0 0 Grade 3/4 chemistry labs 28 (24) 38 (33) 3 (9) 1 (10) Select grade 3-4 laboratory abnormalities

Creatine kinase (CK) 11 (10) 13 (11) 1 (3) 0 Alanine aminotransferase (ALT) 6 (5) 5 (4) 0 0 Lipase 8 (7) 7 (6) 1 (3) 1 (10) Total neutrophils 3 (3) 2 (2) 0 0

•  IntherandomizedQ8W/Q4WIMarms,99%ofISReventsweremild(85%)ormoderate(14%),and87%resolvedwithin7days

•  2/230(<1%)hadanISRthatledtodiscontinuation(bothQ8Wsubjects)throughWeek160

•  NorandomizedIMpatienthadanISRthatledtodiscontinuationafterWeek48

•  IntheoptimizedQ8W/Q4WIMarms,98%ofISReventsweremild(81%)ormoderate(17%),and91%resolvedwithin7days

•  1/44(2%)hadanISRthatledtodiscontinuation(Q4W)

Adverse Events Through Week 160 (cont)


IM,intramuscular;ISR,injection-sitereaction;LA,longacting;Q4W,every4wk;Q8W,every8wk;RPV,rilpivirine.

•  CABLA+RPVLA,dosedQ8WorQ4W,successfullymaintainedHIV-1viralload<50c/mL

•  TheWeek160datademonstratelong-termdurabilityandtolerabilityofbothdosingoptions

•  2patientsonLAdosingmetPDVFcriteria,nosubjectsafterWeek48acrossallarms

•  Goodinjectiontolerabilitywasdemonstratedovertime•  MajorityofISRsweregrade1/2painwithamediandurationof3days

•  ~1%ofpatientshadanISRthatledtodiscontinuationthrough3yearsofdosing

• Q8WandQ4WdosingarebothunderevaluationinongoingphaseIIIstudies

Conclusions


REUNIÃO DO OUTONO - APECS · REUNIÃO DO OUTONO 17 de novembro de 2018 Highlights from Glasgow ....

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