5/14/2015 1 interim results from hcv sprint-1 phase 2 study of boceprevir plus peginterferon...

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Interim Results from HCV SPRINT-1Interim Results from HCV SPRINT-1Phase 2 Study of Boceprevir Plus Peginterferon Phase 2 Study of Boceprevir Plus Peginterferon

alfa-2b/Ribavirin in Treatment-Naïve Subjects with alfa-2b/Ribavirin in Treatment-Naïve Subjects with Genotype-1 CHCGenotype-1 CHC

T. Poynard, MDT. Poynard, MD

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HCV SPRINT-1 InvestigatorsHCV SPRINT-1 Investigators

Luis BalartLuis BalartThomas BoyerThomas BoyerRobert BrownRobert BrownWilliam CassidyWilliam CassidyRaymond ChungRaymond ChungGary DavisGary DavisMitchell DavisMitchell DavisSteven FlammSteven FlammBradley FreilichBradley FreilichJoseph GalatiJoseph GalatiGreg GallerGreg GallerReem GhalibReem GhalibAlexandra GibasAlexandra GibasEliot Godofsky Eliot Godofsky Jorge Herrera Jorge Herrera Ira Jacobson Ira Jacobson Shobha Joshi Shobha Joshi John King John King Paul Kwo Paul Kwo Eric Lawitz Eric Lawitz William Lee William Lee James Levin James Levin

Jonathan McCone Jonathan McCone Timothy Morgan Timothy Morgan Frederick Nunes Frederick Nunes Lisa Marie Nyberg Lisa Marie Nyberg Mary Pat Pauly Mary Pat Pauly Craig Peine Craig Peine Gary Poleynard Gary Poleynard Fred Poordad Fred Poordad David Pound David Pound Natarajan Ravendhran Natarajan Ravendhran Lorenzo Rossaro Lorenzo Rossaro Raymond Rubin Raymond Rubin Michael Ryan Michael Ryan Eugene Schiff Eugene Schiff Kenneth Sherman Kenneth Sherman Mitchell Shiffman Mitchell Shiffman Coleman Smith Coleman Smith Robert Strauss Robert Strauss Mark Sulkowski Mark Sulkowski John Vierling John Vierling Ziad YounesZiad Younes

Frank AndersonFrank Anderson

Jenny HeathcoteJenny Heathcote

Paul Marotta Paul Marotta

Stephen ShafranStephen Shafran

Michael AdlerMichael Adler

Rafael BarcenaRafael Barcena

Thomas Berg Thomas Berg

Marc BourliereMarc Bourliere

Jean-Pierre Bronowicki Jean-Pierre Bronowicki

Giampiero Carosi Giampiero Carosi

Antonio Craxi Antonio Craxi

Rafael Esteban-MurRafael Esteban-Mur

Xavier Forns Xavier Forns

Christophe Hezode Christophe Hezode

Michael Manns Michael Manns

Patrick Marcellin Patrick Marcellin

Fredrik Nevens Fredrik Nevens

Claus Niederau Claus Niederau

Thierry Poynard Thierry Poynard

Jurg Reichen Jurg Reichen

Henk Reesink Henk Reesink

Mario Rizzetto Mario Rizzetto

Christian TrepoChristian Trepo

Stefan Zeuzem Stefan Zeuzem

USUSCanadaCanada EUEU

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Aims of the StudyAims of the Study

To evaluate the most effective To evaluate the most effective treatment strategytreatment strategy in HCV-1 in HCV-1 treatment naïve patientstreatment naïve patients

Duration of therapyDuration of therapy 28 weeks vs. 48 weeks28 weeks vs. 48 weeks

Lead-in strategyLead-in strategy with Peginterferon alfa-2b + ribavirin followed with Peginterferon alfa-2b + ribavirin followed by boceprevir 800 mg TID vs. Triple therapy from Day 1 by boceprevir 800 mg TID vs. Triple therapy from Day 1

Standard vs low dose ribavirin Standard vs low dose ribavirin 800-1400 mg/day vs 400-1000 mg/day800-1400 mg/day vs 400-1000 mg/day

To evaluate the To evaluate the predictability of Week 4 and 12 HCV-RNA predictability of Week 4 and 12 HCV-RNA undetectabilityundetectability on SVR on SVR

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Study DesignStudy Design

PEG 1.5 µg/kg + REBETOL 800-1400 mg + PEG 1.5 µg/kg + REBETOL 800-1400 mg + boceprevir 800 mg TID for 48 weeks boceprevir 800 mg TID for 48 weeks

PEG 1.5 µg/kg + REBETOL 800-1400 mg + PEG 1.5 µg/kg + REBETOL 800-1400 mg + boceprevir 800 mg TID for 48 weeks boceprevir 800 mg TID for 48 weeks

PEG 1.5 µg/kg + REBETOL 800-1400 mg + PEG 1.5 µg/kg + REBETOL 800-1400 mg + boceprevir 800 mg TID for 28 weeksboceprevir 800 mg TID for 28 weeks


No Lead-inNo Lead-in Dosing Strategy Dosing Strategy



Low dose Low dose REBETOLREBETOL

Dosing Strategy Dosing Strategy

PEG 1.5 µg/kg + REBETOL 800-1400 mg PEG 1.5 µg/kg + REBETOL 800-1400 mg for 48 weeksfor 48 weeks

PEG 1.5 µg/kg + REBETOL 800-1400 mg PEG 1.5 µg/kg + REBETOL 800-1400 mg for 48 weeksfor 48 weeksControlControl

PEG 1.5 µg/kg + REBETOL 800-1400 mg + boceprevir 800 mg TID for 24 weeks




PEG-INTRON + PEG-INTRON + REBETOL 800-1400 mg REBETOL 800-1400 mg

x 4 weeksx 4 weeks


x 4 weeksx 4 weeks


x 4 weeksx 4 weeks


x 4 weeksx 4 weeks

Lead-inLead-in Dosing Strategy Dosing Strategy

Follow-up Follow-up x 44 weeksx 44 weeksFollow-up Follow-up x 44 weeksx 44 weeks






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SVR Data Available for Interim AnalysisSVR Data Available for Interim Analysis



No Lead-inNo Lead-in Dosing Strategy Dosing Strategy




x 4 weeksx 4 weeks


x 4 weeksx 4 weeks

Lead-inLead-in Dosing Strategy Dosing Strategy



SVR 12SVR 12

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Baseline CharacteristicsBaseline Characteristics

P/R lead-in→ P/R lead-in→ P/R/boceprevir,P/R/boceprevir,

N=103N=103‡‡

P/R/boceprevir,P/R/boceprevir,N=107N=107

P/R Control,P/R Control,N=104N=104

GenderGender

Male (%)Male (%) 5050 5959 6767

RaceRace

Caucasian (%)Caucasian (%) 8383 8080 8080

Mean age (years)Mean age (years) 47.747.7 46.446.4 48.348.3

Mean weight (kg)Mean weight (kg) 79.979.9 83.483.4 83.483.4

HCV Subtype (%)HCV Subtype (%)

1a1a 5151 6363 5151

1b1b 3636 2828 4040

Viral load mean (logViral load mean (log1010 IU/mL) IU/mL) 6.56.5 6.66.6 6.56.5

HCV-RNA >600,000 IU/mL (%)HCV-RNA >600,000 IU/mL (%) 8787 9292 9090

Cirrhosis (%)Cirrhosis (%) 77 77 88

‡ ‡ Boceprevir added to treatment regimen after 4 week lead-in of PEG-IFN Boceprevir added to treatment regimen after 4 week lead-in of PEG-IFN αα-2b + ribavirin.-2b + ribavirin.

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HCV-1 Patients with Undetectable HCV-RNA* at HCV-1 Patients with Undetectable HCV-RNA* at Weeks 4 and 12 of Boceprevir Therapy (ITT)Weeks 4 and 12 of Boceprevir Therapy (ITT)

60

78

39

73

8

34

0

20

40

60

80

100

Week 4 Undetectable HCV-RNA Week 12 Undetectable HCV-RNA

% o

f p

ati

en

ts

* Roche TaqMan 1.0 (LLD 15 IU/mL)* Roche TaqMan 1.0 (LLD 15 IU/mL)‡ ‡ Boceprevir added to treatment regimen after 4 week lead-in of PEG-IFN Boceprevir added to treatment regimen after 4 week lead-in of PEG-IFN αα-2b + ribavirin.-2b + ribavirin.

P/R lead-in → P/R/boceprevir, N=103‡ P/R/boceprevir, N=107 P/R control, N=104

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Just Available Data Just Available Data SVR for 28/48 Weeks and Peg/riba ControlSVR for 28/48 Weeks and Peg/riba Control

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Sustained Virologic Response*Sustained Virologic Response*for 28/48 Weeks and P/R Control for 28/48 Weeks and P/R Control

*SVR 12 or later timepoint*SVR 12 or later timepoint‡‡ Boceprevir added to treatment regimen after 4 week lead-in of PEG-IFN Boceprevir added to treatment regimen after 4 week lead-in of PEG-IFN αα-2b + ribavirin.-2b + ribavirin.

56

74

55

66

38

0

20

40

60

80

100

P/R lead-in →P/R/boc

P/R lead-in →P/R/boc

P/R/boc P/R/boc P/R

% o

f p

ati

en

ts w

ith

un

de

tec

tab

le H

CV

-RN

A

28 Wks 28 Wks n=103n=103

48 Wks 48 Wks n=103n=103

28 Wks 28 Wks n=107n=107

48 Wks 48 Wks n=103n=103

48 Wks 48 Wks n=103n=103

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Safety for 28 Weeks of TreatmentSafety for 28 Weeks of Treatment

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Treatment DiscontinuationsTreatment Discontinuations x 28 Weeks x 28 Weeks


N=103 (%)N=103 (%)‡‡

P/R/boceprevir,P/R/boceprevir,N=107 (%)N=107 (%)

P/R Control,P/R Control,N=104 (%)N=104 (%)

Total DiscontinuedTotal Discontinued 27 (26)27 (26) 30 (28)30 (28) 15 (14)15 (14)

Adverse EventsAdverse Events 15 (15)15 (15) 12 (11)12 (11) 8 (8)8 (8)

Viral BreakthroughViral Breakthrough 4 (4)4 (4) 7 (7)7 (7) 00

Other*Other* 8 (8)8 (8) 11 (10)11 (10) 7 (7)7 (7)

* Lost to Follow Up, Subject Did Not Wish to Continue, Non-compliance with Protocol * Lost to Follow Up, Subject Did Not Wish to Continue, Non-compliance with Protocol ‡‡ Boceprevir added to treatment regimen after 4 week lead-in of PEG-IFN Boceprevir added to treatment regimen after 4 week lead-in of PEG-IFN αα-2b + ribavirin.-2b + ribavirin.

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Most Common Adverse Events x 28 WeeksMost Common Adverse Events x 28 Weeks(≥15% in any Arm)(≥15% in any Arm)


N=103 (%)N=103 (%)‡‡

P/R/boceprevir,P/R/boceprevir,N=107 (%)N=107 (%)

P/R Control,P/R Control,N=104 (%)N=104 (%)

FatigueFatigue 6868 6161 5555

AnemiaAnemia 5353 5555 3434

NauseaNausea 4141 3838 4343

HeadacheHeadache 4040 4949 4242

ChillsChills 3030 2929 3434

AlopeciaAlopecia 2929 3434 2626

InsomniaInsomnia 2828 3434 3737

PyrexiaPyrexia 2626 2626 3434

Diarrhea Diarrhea 2626 2626 2323

Dysgeusia Dysgeusia 2626 2121 99

IrritabilityIrritability 2323 2323 2222

ArthralgiaArthralgia 2121 1313 1818

CoughCough 2121 1717 1818

Influenza-Like Illness Influenza-Like Illness 2020 2222 2323

NeutropeniaNeutropenia 1717 2323 1212

PruritisPruritis 1818 1818 1515

DizzinessDizziness 1616 1818 1515

DyspnoeaDyspnoea 1212 1717 1414

AnxietyAnxiety 99 1616 1818

Dry skinDry skin 88 1111 1616

‡‡ Boceprevir added to treatment regimen after 4 week lead-in of PEG-IFN Boceprevir added to treatment regimen after 4 week lead-in of PEG-IFN αα-2b + ribavirin.-2b + ribavirin.

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Skin and Subcutaneous Disorders* x 28 WeeksSkin and Subcutaneous Disorders* x 28 Weeks

37

28

8

3429

50

3830

801§

0

20

40

60

80

100

All Mild Moderate Severe

% o

f p

ati

en

ts

*Includes rash (all types), eczema, erythema, photosensitivity reaction, dermatitis, skin irritation and skin exfoliation.*Includes rash (all types), eczema, erythema, photosensitivity reaction, dermatitis, skin irritation and skin exfoliation.§§ Severe Erythema. Patient was in PEG-IFN Severe Erythema. Patient was in PEG-IFN αα-2b + ribavirin lead in; never received boceprevir-2b + ribavirin lead in; never received boceprevir‡‡ Boceprevir added to treatment regimen after 4 week lead-in of PEG-IFN Boceprevir added to treatment regimen after 4 week lead-in of PEG-IFN αα-2b + ribavirin.-2b + ribavirin.


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Hemoglobin: Worst WHO Grade Category Hemoglobin: Worst WHO Grade Category Observed During Treatment x 28 WeeksObserved During Treatment x 28 Weeks††

23

50

27

0 0

21

54

25

1 0

45 46

10

0 00

20

40

60

80

100

Grade 0 (≥ 11.0 g/dl)

Grade 1 (9.5-<11.0 g/dl)

Grade 2 (8.0-<9.5 g/dl)

Grade 3 (6.5-<8.0 g/dl)

Grade 4 (<6.5 g/dl)

% o

f p

ati

en

ts


† † Epoetin-alfa use allowed; 48% in P/R lead-in, 45% in P/R/boceprevir, 25% in P/R controlEpoetin-alfa use allowed; 48% in P/R lead-in, 45% in P/R/boceprevir, 25% in P/R control‡‡ Boceprevir added to treatment regimen after 4 week lead-in of PEG-IFN Boceprevir added to treatment regimen after 4 week lead-in of PEG-IFN αα-2b + ribavirin.-2b + ribavirin.

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Summary of Interim ResultsSummary of Interim Results

Boceprevir with P/R X 28 and 48 weeks Boceprevir with P/R X 28 and 48 weeks Greater SVR than P/R alone X 48 weeks in HCV-1 naïve Greater SVR than P/R alone X 48 weeks in HCV-1 naïve

patients.patients.1-41-4

Safety Safety Boceprevir containing regimens appear to be well-Boceprevir containing regimens appear to be well-

tolerated.tolerated. Incidence of rash and pruritis comparable to Control.Incidence of rash and pruritis comparable to Control. No boceprevir-defining toxicity responsible for treatment No boceprevir-defining toxicity responsible for treatment

discontinuation.discontinuation.

11 Fried M, et al. Fried M, et al. N Engl J MedN Engl J Med 2002;347:975-82. 2002;347:975-82. 22 Manns M, et al. Manns M, et al. Lancet Lancet 2001; 358: 958–65.2001; 358: 958–65.33 Sulkowski M, et al. Abstract #LB 2, EASL 2008. Sulkowski M, et al. Abstract #LB 2, EASL 2008. 4 4 Jacobson I, et al. Jacobson I, et al. HepatologyHepatology 2007;46:982-990. 2007;46:982-990.

5/14/2015 1 interim results from hcv sprint-1 phase 2 study of boceprevir plus peginterferon...

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