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EASL Highlights 2017

Jürgen Rockstroh Department of Medicine I

University Hospital Bonn, Bonn, Germany

13th International Workshop on

Coinfection HIV & Hepatitis,

Wednesday 21st June 2017, Lisbon,

Portugal

• Honoraria for lectures and/or consultancies from Abbott,

AbbVie, Bionor, BMS, Cipla, Gilead, Janssen, Merck,

Roche, ViiV.

• Research grants from Dt. Leberstiftung, DZIF, NEAT ID.

Conflict of Interest: JKR

EASL 2017

» WHO global hepatitis report

» New EASL HBV guidelines

» TDF TAF

» HBV cure agenda

» HBV reactivation under DAA therapy

» HCC risk following DAA therapy

» DAA therapy in children

» HCV therapy in real-life cohorts

» New DAAs

» Treatment of HCV patients after DAA failure

» HCV elimination studies

Seite 3

STATUS OF HEPATITIS B HBV

Sources – WHO (LSHTM)

Prevalence: 257 million people living with HBV

68% in Africa /Western Pacific

Incidence: Chronic HBV infection in children under 5 reduced from 4.7% to 1.3% (immunization)

Incidence: 1.75 million new infections / year (Unsafe health care and injection drug use)

Prevalence: 71 million infected, all regions

STATUS OF HEPATITIS C HCV

Sources – WHO (Center for Disease Analysis )

HEPATITIS MORTALITY IS INCREASING

Sources – WHO Global Health Estimates

HBV HCV HAV HEV

0

0.5

1

1.5

2

2000 2005 2010 2015

Mill

ion

s o

f d

eath

s

Year

96% hepatitis deaths from HBV and HCV (cirrhosis and hepatocellular carcinoma)

Hepatitis

Tuberculosis

HIV

Malaria

1.34 million deaths in 2015

EASL 2017

Seite 7

Do we really need all

this complexity?

EASL HBV Guidelines 2017

HBV

Seite 9

HBV

Seite 10

HBV

Seite 11

LDV/SOF for 12 weeks in patients with HCV/HBV coinfection 111 HCV GT 1 and 43 HCV GT 2 Patients were enrolled

67% Treatment naïve, non cirrhotics 85%

All but one HBeAg negative

No patients experienced clinical signs or symptoms of HBV reactivation

63% (70/111) of pts had asymptomatic HBV DNA reactivation

No patient had AEs of jaundice, liver decompensation, liver failure, or LT

Multivariate analysis: Factors associated with HBV clinical reactivation (>1 log10 ↑ in HBV DNA and ALT >2x ULN)

Mean (range) No (n=106) Yes (n=5) p-value

BL ALT, U/L 64

(17–281) 149

(40–228) 0.0032

BL HBV DNA, log10IU/mL 2.05

(1.28–5.83)

2.97 (1.54–5.46)

0.0188

Liu C-J, et al. EASL 2017, Amsterdam. #PS-098

Risk of HBV reactivation in chronic HBsAg +ve patients during DAAs therapy for HCV : A Phase 3 Study in Taiwan

A) Patient with tumor size < 2.5 cm and without history of prior HCC recurrences; B) Patient without tumor size < 2.5 cm and with history of prior HCC recurrences; C) Patient with tumor size < 2.5 cm and without history of prior HCC recurrences; D) Patient with tumor size > 2.5 cm and history of prior HCC recurrences.

Cabibbo G et al. EASL 2017, Poster THU-096

Risk of Hepatocellular Carcinoma (HCC) recurrence in HCV cirrhotic patients treated with DAAs.

HCC recurrence following SVR

RR non adjusted RR adjusted IC 95 % P value

Average follow-up 0,86 0,79 0,55-1,15 0,19

Average Age 1,11 1,11 0,96-1,27 0,14

Treatment 1,36 0,62 0,11-3,45 0,56

Hagihara, 2011

0,05

HCC recurrence rate/100 personne-years

Authors, year ES (IC 95 %) Weight, %

50

Kanogawa, 2015

Kunimoto, 2016

Jeong, 2007

Saito, 2014

Sanefuji, 2009

Minami, 2016

Global (I-squared = 0,0 %, p = 0,638)

9,15 (4,58-18,30)

6,49 (3,49-12,05)

7,87 (4,82-12,84)

13,26 (7,14-24,65)

12,88 (6,14-27,01)

13,33 (4,30-41,34)

8,10 (4,05-16,19)

9,21 (7,18-11,81)

12,90

16,13

25,81

16,13

11,29

4,84

12,90

IFN AAD

Conti, 2016

Authors, year

Pol CO22, 2016

Pol CO12, 2016

Pol CO23, 2016

Reig, 2016

Rinaldi, 2016

Minami, 2016

Torres, 2016

Zavaglia, 2016

Lei-Zeng, 2016


0,05

HCC recurrence rate /100 personne-years

50 100

45,82 (28,49-73,71)

8,11 (5,43-12,10)

4,40 (0,62-31,20)

2,82 (1,35-5,92)

54,24 (33,23-88,53)

26,67 (3,76-189,31)

20,98 (9,43-46,70)

0,07 (0,00-2,28e+07)

1,42 (0,20-10,07)

0,08 (0,00-2,60e+07)

12,14 (5,00-29,46)

14,96

15,15

8,86

14,10

14,92

8,86

13,87

0,20

8,86

0,20

ES (IC 95 %) Weight, %

HCC Risk after DAAs treatments : meta-analysis

Meta regression of HCC recurrence

Waziry R et al. EASL 2017, Abs. PS-160

Occurrence of HCC in patients with HCV related liver disease treated with DAAs

• RESIST-HCV: Prospective Sicilian cohort

– 2466 patients with cirrhosis + DAA treatment

– Liver US every 6 months 14 month observation period after starting DAAs

• 78 de novo HCCs (3.1%) over median 14 months

– SVR, incidence 2.4%; no SVR, incidence, 7.5%

– Within Milan criteria: SVR, 84.4%; no SVR 42.8%

• SVR was not associated with increased risk of HCC nor with more ‘aggressive’ patterns

• Predictors include low albumin (

HCC occurrence following SVR

Meta regression of HCC occurrence

Waziry R et al. EASL 2017, Abs. PS-160

Ogawa, 2013 D’ambrosio, 2011 Bruno, 2009 Mallet, 2006 Cardoso, 2010 Yu, 2006 Hung, 2006 Morgan, 2010 Aleman, 2013 Chenquer, 2010 Moon, 2015 Fernandez-Rodriguez, 2010 Janjua, 2016 Rutter, 2015 Velosa, 2011 Nahon, 2017 Marco, 2016 Global (I-squared = 45,7 %, p = 0,21)

0,01 30

HCC occurrence rate /100 personne-years

3,67 (1,75-7,70) 0,71 (0,23-2,20) 1,74 (0,83-3,64) 0,78 (0,25-2,43) 1,66 (0,75-3,70) 2,04 (1,06-3,93) 2,22 (0,92-5,34) 0,20 (0,05-0,80) 1,03 (0,46-2,29) 0,98 (0,14-6,98) 1,12 (0,16-7,94) 0,99 (0,41-2,37) 0,74 (0,33-1,64) 0,95 (0,48-1,91) 0,36 (0,05-2,56) 0,88 (0,61-1,28) 0,85 (0,41-1,78) 1,14 (0,86-1,52)

7,34 4,41 7,34 4,41 6,78 8,25 6,12 3,27 6,78 1,84 1,84 6,12 6,78 7,83 1,84

11,70 7,34

Authors, year ES (IC 95 %) weight, % IFN

Cardoso, 2016

Conti, 2016

Rinaldi, 2016

Kozbal, 2016

Lei-Zeng, 2016

Romano, 2016

Affronti, 2016

Muir, 2016

Carrat, 2016


0,01

HCC occurrence rate/100 personne-years

30

DAA

7,41 (2,78-19,74)

4,51 (2,35-8,67)

10,29 (4,91-21,59)

1,80 (0,97-3,35)

0,04 (0,00-1,30e+07

1,78 (1,22-2,59)

3,33 (1,25)

0,12 (0,02-0,85)

3,30 (2,67-4,08)

3,09 (1,92-4,96)

10,33

13,68

12,74

14,05

0,06

16,55

10,33

4,44

17,83

Unadjusted RR Adjusted RR IC 95 % p

Average follow-up 0,88 0,77 0,62-0,97 0,03

Average age 1,11 1,06 0,99-1,14 0,08

Treatment 2,77 0,75 0,22-2,52 0,62

ES (IC 95 %) weight, %

HCC Risk after DAAs treatments : meta-analysis

LDV/SOF ± RBV in Children 6–11 Years Old

LDV/SOF 45/200 mg tablet; RBV dosed using a weight-based algorithm.

Murray, EASL 2017, PS-101

Open-label study of LDV/SOF (45 mg/ 200 mg) fixed dose combination tablet (once daily) ± RBV (15 mg/kg/day up to 1400 mg/day) for 12 or 24 weeks in children aged 6 to 11 years

LDV/SOF ± RBV n=90

Mean age, y (range) 9 (6–11)

Male, n (%) 53 (59)

White, n (%) 71 (79)

HCV GT 1 / 3 / 4, % 96 / 2 / 2

Mean baseline HCV RNA, log10 IU/mL (range)

6.0 (4.6–7.3)

Treatment experienced, n (%) 18 (20)

Cirrhosis, n (%) 2 (2)

SV

R1

2, %

99 100 100

0

20

40

60

80

100

LDV/SOF12 Wk

LDV/SOF24 Wk

LDV/SOF+RBV24 Wk

86/87 1/1 2/2

1 relapse

Half dose LDV/SOF ± RBV resulted in high SVR12 rates and was well tolerated in 6 to 11 years old patients

Grade 2 AEs: Dental abscess, abdominal pain, gastroenteritis. None

were considered drug related

No treatment DC due to AE

Baseline Demographics SVR12

Real life cohorts

Seite 18

HCV therapy in real life

cohorts shows comparable

SVR rates to clinical trials

with excellent safety results

In vitro:1,2

• High barrier to resistance

• Potent against common NS3 polymorphisms (e.g., positions 80, 155, and 168) and NS5A polymorphisms (e.g., positions 28, 30, 31 and 93)

• Synergistic antiviral activity

Clinical PK & metabolism:

• Once-daily oral dosing with food

• Minimal metabolism and primary biliary excretion

• Negligible renal excretion (

EXPEDITION-1 Study: Objective and Study Design

Objective

» Evaluate the efficacy and safety of G/P for 12 weeks in patients

with HCV GT1, 2, 4, 5 or 6 infection and compensated cirrhosis

Open-label Treatment

G/P is coformulated and dosed once daily as three 100 mg/40 mg pills for a total dose of

300 mg/120 mg.

0 Week 24 Week 36 Week 12

G/P 300 mg/120 mg

N=146

SVR12

assessment

Forns X, et al. 52nd EASL; Amsterdam, Netherlands; April 19-23, 2017. Abst. GS-006.

Patients were enrolled at

40 study sites in Belgium,

Canada, Germany, South

Africa, Spain, and the

United States

EXPEDITION-1 Study:

Baseline Demographics and

Clinical Characteristics

Characteristic 12-week G/P

N = 146 Male, n (%) 90 (62)

Age, median (range), years 60 (26−88)

White race,* n (%) 120 (82)

BMI, median (range), kg/m2 29 (18−55)

HCV genotype, n (%)†

1a 48 (33)

1b 39 (27)

2 34 (23)

4 16 (11)

5 2 (1)

6 7 (5)


G/P, glecaprevir/pibrentasvir; BMI, body mass index

*Race and ethnicity are self-reported

†Genotype determined by the Versant HCV Genotype Inno-LiPA Assay Version 2.0

EXPEDITION-1 Study:

Baseline Demographics and

Clinical Characteristics (Cont’d)

12-week G/P N = 146

HCV RNA, median (range) log10 IU/mL 6.1 (3.1−7.4)

Treatment-naïve 110 (75)

Treatment-experienced 36 (25)

IFN-based (IFN/pegIFN ± RBV) 25 (69)

SOF-based (SOF + RBV ± pegIFN ) 11 (31)

Platelet count

EXPEDITION-1 Study:

SVR12 by Intent-to-Treat

(ITT) Analysis


*Patient with HCV GT1a infection relapsed at PTW8 - No treatment-emergent substitutions were present in NS3

- In NS5A, Y93N was present at baseline; Y93N, Q30R and H58D were present at the time of failure

99 100 100 100 100 99

0

20

40

60

80

100

GT1 GT2 GT4 GT5 GT6 Total

% P

atie

nts

wit

h S

VR

12

89

90

31

31

16

16 2

2 7

7

145

146

EXPEDITION-1 Study:

Summary of Adverse

Events (AE)

Event, n (%) 12-week G/P

N=146

Any AE 101 (69)

Any serious AE 11 (8)

DAA-related serious AE 0

Any AE leading to discontinuation of

study drug 0

Death* 1 (0.7)

Common AEs (occurring in ≥10% of patients)

Fatigue 28 (19)

Headache 20 (14)

Pruritus 14 (10)

HCC 2 (1)


DAA, direct-acting antiviral; HCC, hepatocellular carcinoma *Patient had a history of hemophilia and died post-treatment due to a cerebral hemorrhage assessed by the investigator as not related to the study drug

EXPEDITION-2 Study:

Objective and Study Design

Objective

EXPEDITION-2 is a phase 3, multi-center global study evaluating

8- or 12-week treatment with G/P in HCV/HIV-1 co-infected adults

without or with compensated cirrhosis, respectively

Study Design

Rockstroh J, et al. 52nd EASL; Amsterdam, Netherlands; April 19-23, 2017. Abst. LBP-522

8-week G/P N=137

(no cirrhosis)

12-week G/P N=16

(with cirrhosis)

SVR12

SVR12

Day

0 Week

8

Week

12

Week

20

Week

24 Post-treatment

Week 24

Open-label

Treatment

EXPEDITION-2 Study:

Efficacy Results

Rockstroh J, et al. 52nd EASL; Amsterdam, Netherlands; April 19-23, 2017. Abst. LBP-522

mITT, modified ITT population, which excludes patients with non-virologic failure.

*One patient achieved SVR4 but as lost to follow-up due to homelessness and did not return for PTW12 visit

• The SVR12 rate in the mITT population of patients with cirrhosis treated for 12 weeks was 93% (14/15); 1 patient with GT3a infection and cirrhosis had on-treatment virologic failure at treatment Week 8:

• NS3: no polymorphisms at baseline; Y56H at failure

• NS5A: A30V at baseline; S24F & M28K at failure; (A30V not detected)

• The SVR12 rate was 100% (136/136) in patients without cirrhosis treated for 8 weeks

99 98 99 99

0

20

40

60

80

100

SVR4 SVR12

% P

atie

nts

Wit

h S

VR

12

ITT

mITT

Breakthrough 1 1

Relapse 0 0

Missing Data 0 1*

Discontinued 1 1

151

153

151

152

150

153 150

151

8

*Endpoint was tested only after 12 weeks of G/P was determined non-inferior to 12 weeks of SOF + DCV

Foster G, et al. 52nd EASL; Amsterdam, Netherlands; April 19-23, 2017. Abst. GS-007.

ENDURANCE-3 Study:

Objective and Study Design

SVR12

Arm B N = 115

Arm A N = 233

Weeks

SVR12

0 12

G/P

20

Treatment Period

(1)

no

n-i

nfe

rio

rity

24

Post-treatment Period

Arm C N = 157 G/P

SOF + DCV SVR12 2:1 R

and

om

ized

(2)

no

n-i

nfe

rio

rity

• Arm C: 8-week treatment duration

• Per discussion with regulatory authorities after phase 2 treatment data became available, an 8 week treatment Arm of G/P was added to the study design • SVR12: Non-inferiority of 8 weeks of G/P compared to 12 weeks of G/P*

Characteristic G/P

12 weeks N = 233

SOF + DCV 12 weeks N = 115

G/P 8 weeks N = 157

Male, n (%) 121 (52) 52 (45) 92 (59)

White race, n (%) 205 (88) 103 (90) 134 (85)

Age, median years (range) 48 (22 – 71) 49 (20 – 70) 47 (20 – 76)

BMI, median kg/m2 (range) 25 (17 – 49) 25 (18 – 42) 26 (18 – 44)

HCV RNA, median log10 IU/mL (range)

6.1 (3.5 – 7.5) 6.0 (3.8 – 7.4) 6.1 (1.2 – 7.6)

History of injection drug use, n (%) 149 (64) 73 (63) 104 (66)

Baseline fibrosis stage, n (%)

F0 – F1 201 (86) 97 (84) 122 (78)

F2 12 (5) 8 (7) 8 (5)

F3 20 (9) 10 (9) 27 (17)

Subtype GT3a, n/N (%)* 226/229 (99) 113/113 (100) 154/155 (99)


ENDURANCE-3 Study:

Baseline Demographics

and Clinical Characteristics

BMI, body mass index; DCV, daclatasvir; G/P, coformulated glecaprevir/pibrentasvir; GT, genotype; HCV, hepatitis C virus; SOF, sofosbuvir *HCV subtype determined by phylogenetic analysis; N = total number of patients with sequence data available

2:1 randomized Non-randomized


ENDURANCE-3 Study: Results

SVR12 by Intent-to-Treat (ITT)

Analysis

*Conventional statistical methods were used in multiplicity comparison for determining non-inferiority

Non-inferiority:

• Lower bound of the confidence interval (CI) of the difference in SVR12 must be above -6%* • (1) -1.2% (95% CI -5.6 –

3.1) • (2) -0.4% (97.5% CI -5.4 –

4.6)

• Both G/P treatments met non-inferiority criteria for the primary endpoint

95 97 95

0

20

40

60

80

100

SVR

12

(%

Pat

ien

ts)

Treatment Duration

G/P 12 weeks

SOF + DCV 12 weeks

G/P 8 weeks

222

233

111

115 149

157

(2) non-inferior

(1) non-inferior

Outcome, n (%)

G/P 12 weeks N = 233

SOF + DCV 12 weeks N = 115

G/P 8 weeks N = 157

Sustained virologic response 222 (95) 111 (97) 149 (95)

Virologic Failure

Breakthrough 1 (

SVR12 by baseline polymorphisms, n/N (%)

G/P 12 weeks

SOF + DCV* 12 weeks

G/P 8 weeks

NS3 only 26/26 (100) – 14/15 (93)

NS5A only 35/36 (97) 20/21 (95) 34/36 (94)

NS3 + NS5A 6/7 (86) – 5/7† (71)

None 151/153 (99) 89/89 (100) 94/95 (99)

2:1 randomized Non-randomized


ENDURANCE-3 Study:

Resistance Analysis

» Overall, 97% (mITT analysis; 371/381) of GT3 infected patients receiving G/P achieved

SVR12

» 3% of patients (n = 10) had virologic failure

Common baseline polymorphisms: NS3 A166S‡ (n = 3); NS5A A30K‡ (n=5)

Common substitutions at failure: A30K+Y93H (n = 5); confers 69-fold resistance to PIB

G/P for 8 weeks: 5/5 (100%) patients with Y93H at baseline achieved SVR12

Patients that prematurely discontinued treatment or were lost to follow-up were not included in the analysis Polymorphisms detected by next-gen sequencing using 15% detection threshold at amino acid positions: NS3: 36, 56, 80, 155, 156, 166, 168; NS5A: 24, 28, 29, 30, 31, 32, 58, 92, 93 *NS3 sequences of samples were not determined †One patient who had virologic failure had poor adherence and baseline polymorphisms in both NS3 and NS5A ‡Does not confer resistance to GLE or PIB

Poordad F, et al. 52nd EASL; Amsterdam, Netherlands; April 19-23, 2017. Abst. PS-156.

MAGELLAN-1, Part 2 Study:

Results: SVR12 by DAA

Class in Prior Therapy Overall SVR12:

» 12-week: 89% (39/44)

» 1 OTVF; 4 relapse

» 16-week: 91% (43/47)

» 1 OTVF; 0 relapse

Prior Treatment History

» PI: TVR, SMV, BOC

» NS5A: LDV, DCV

» NS5A+PI: OBV and PTV,

or other combinations

» OTVF, on-treatment

virologic failure

100 88 79 100 94 81

0

20

40

60

80

100

SVR

12

(%

Pat

ien

ts)

Prior DAA PI NS5A PI+ PI NS5A PI+

Class only only NS5A only

only NS5A

Regimen G/P: 12 weeks G/P: 16 weeks

14

14 14

16

11

14

13

13

17

18

13

16

Pangenotypic Single Tablet Regimen

(STR) with Inhibitors of HCV NS5B

(Nucleotide) + NS5A + NS3

Sofosbuvir (SOF)/Velpatasvir (VEL)

» SOF: Nucleoside polymerase inhibitor

with activity against HCV GT 1-6

» VEL: Potent pangenotypic

NS5A inhibitor

Voxilaprevir (VOX)

» HCV NS3/4A Pl with potent antiviral

activity against GT 1-6, including

most RASs

SOF/VEL/VOX

» Once daily, oral, fixed-dose

combination (400/100/100 mg) for GT

1-6

Bourlière M, et al. 67th AASLD; Boston, MA; November 11-15, 2016; Abst. 194.

VEL NS5A inhibitor

SOF Nucleotide polymerase

inhibitor

VOX NS3/4A protease inhibitor

VEL NS5A inhibitor

SOF Nucleotide polymerase

inhibitor

VOX NS3/4A protease inhibitor

Efficacy of SOF/VEL/VOX for 12

Weeks in DAA-Experienced Patients

Breakthrough 1* 1 1 0 0 0 0 0 0 0

Relapse 7 2 2 0 0 4 1 0 0 0

Other 6 3 2 1 0 2 1 0 0 0

*Patient had drug levels consistent with nonadherence.

Roberts, EASL 2017, SAT-280

Integrated Efficacy Analysis of POLARIS-1 and -4

97 97 97 99 100 96 95 100 100 100

0

20

40

60

80

100

SV

R12,

%

GT 4

1

1

431

445

150

155

36

36

126

132

39

41

222

228

Total GT 1

Total

GT 1a GT 1b GT 2 GT 3 GT 5 GT 6 Other

1

1

6

6

68

69

The SVR12 rate was 97% (431/445) in DAA-experienced patients treated with

SOF/VEL/VOX for 12 weeks; Rates were similar regardless of genotype

Resistance Analysis of

SOF/VEL/VOX for 12 Weeks in

DAA-Experienced Patients

Sarrazin, EASL 2017, THU-248

Integrated Resistance Analysis of POLARIS-1 and -4

High SVR12 rates regardless of presence of baseline RASs in DAA-

experienced patients treated with SOF/VEL/VOX for 12 weeks

POLARIS-1:

DAA-experienced patients who had

previously received NS5A inhibitor

POLARIS-4:

DAA-experienced patients who had not

received NS5A inhibitor

4%

NS3 9/248

17%

No RASs 43/248

50%

NS5A 124/248

29%

NS3+NS5A 72/248

97% SVR12

199/205

98% SVR12

42/43

100%

SVR12

83/83

51%

No RASs 86/169 24%

NS5A 40/169

2%

NS3+NS5A 4/169

99%

SVR12

85/86

23%

NS3 39/169

C-SURGE Study:

Grazoprevir + Ruzasvir

+ Uprifosbuvir

» Co-formulated as a fixed-dose combination tablet; administered as 2 tablets once-

daily for a total daily dose of 100 mg grazoprevir (GZR), 60 mg ruzasvir (RZR), and

450 mg of uprifosbuvir (UPR; MK -3682)

» GZR + RZR + UPR has been shown to be effective, safe, and well tolerated for

treatment-naïve and peg-interferon/ribavirin-treatment experienced HCV GT1, 2 and

3-infected persons with SVR rates >90%

Grazoprevir (GZR)

Ruzasvir (RZR)

Uprifosbuvir (UPR)

• HCV NS3/4A protease inhibitor

• 50 mg per tablet

• HCV NS5A inhibitor3


• HCV NS5B nucleotide polymerase inhibitor


Gane EJ et al., EASL, abstract SAT-139, 2016 Gane EJ et al., AASLD, abstract LB-15, 2015 Tong, et al., J Med Chem 60:290, 2017

C-SURGE Study:

Study Design » This multicenter, open-label trial randomized 94 HCV GT1-infected participants

who relapsed after a regimen of LDV/SOF or EBR/GZR (randomized 1:1;stratified

by GT1a/1b and cirrhosis)

SVR12* 1° Endpoint

GZR:100 mg once-daily; RZR: 60 mg once-daily; UPR: 450 mg once-daily; TW+ treatment week; FW=follow-up week; LDV=ledipasvirl SOF=sofosbuvir. *SVR12 = HCV RNA 105 kg=1400 mg/d). Individuals could not be compensated cirrhotic (platelet cutoff+75,000/μL; excluded Child-Pugh B & C) or non-cirrhotic individuals.

GZR + RZR + UPR + RBV† (16 weeks), n=45

GZR + RZR + UPR (24 weeks), n=49

D1 TW8 TW16 TW24 FW12

Wedemeyer H, et al. 52nd EASL; Amsterdam, Netherlands; April 19-23, 2017. Abst. PS-159.

Wedemeyer D , et al. 52nd EASL; Amsterdam, Netherlands; April 19-23, 2017. Abst. PS-159.

Demographics 16 Weeks + RBV,

n=44* 24 Weeks without RBV,

n=49 Overall GT1

N=93*

Male, n (%) 37 (84) 43 (88) 80 (86)

Age, median years, (range) 61.0 (33 to 70) 60.0 (25 to 71) 60.0 (25 to 71)

Race, White, n (%) 31 (71) 37 (76) 68 (73)

HCV Genotype 1a, n (%) 40 (91) 40 (82) 80 (86)

Non-cirrhotic, n (%) Cirrhotic, n (%)

25 (57) 19 (43)

27 (55) 21 (43)†

52(56) 40 (43)

NS5A RASs at baseline, n (%)ǂ NS3 RASs at baseline, n (%)ǂ

32 (79) 25 (57)

46 (94) 35 (71)

78 (84) 60 (65)

Baseline HCV RNA >2,000,000 IU/mL, n (%)

29 (66) 33 (67) 62 (67)

Median baseline HCV RNA (log10IU/mL) 6.5 6.4 6.5

Previously failed: 12-24 weeks of LDV/SOF 8 weeks of LDV/SOF 12 weeks of EBR/GZR

26 (59) 9 (20) 9 (20)

31 (63) 5 (10)

13 (27)

57 (61) 14 (15) 22 (24)

* Does not include 1 participant in the 16 week + RBV arm who withdrew prior to beginning treatment. Cirrhosis = Liver biopsy at any time showing cirrhosis, Fibroscan result of >12.5kPa within 12 month of enrollment, or Fibrotest >0.75 and APRI >2 at time of enrollment. † One participant in 24 week arm had unknown cirrhosis status ǂ NS5A RASs = any change from wild-type at 4 positions (28, 30, 31, or 93). NS3 RASs = any change from wild-type at 14 positions (36, 54, 55, 56, 80, 107, 122, 132, 155, 156, 168, 170, or 175). RASs detected by next generation sequencing performed with a 15% sensitivity threshold.

C-SURGE Study:

Demographics

98 100 100 100

0

20

40

60

80

100

16 weeks + RBV 24 weeks (no RBV)

SVR

12

(%

wit

h H

CV

RN

A <

15

IU

/mL;

9

5%

CI)

Full Analysis Set Modified Full Analysis Set

43

44

43

43

*

49

49 49

49

C-SURGE Study:

Efficacy Results

SVR12 = % of participants with HCV RNA

Tolerability 16 Weeks + RBV,

n=44 24 Weeks Without RBV,

n=49 Overall GT1

N=93

One or more AEs, n (%) 40 (91) 39 (80) 79 (85)

Drug-related AE, n (%) 32 (73) 23 (47) 55 (59)

Serious AE, n (%) 1 (2) 4 (8) 5 (5)*

Drug-related serious AE, n (%) 0 (0) 0 (0) 0 (0)

Death, n (%) 0 (0) 0 (0) 0 (0)

Discontinuation due to AE, n (%) 0 (0) 0 (0) 0 (0)

Hemoglobin 5x baseline, n (%) 0 (0) 0 (0) 0 (0)

Late ALT/AST >5x ULN, n (%) 0 (0) 0 (0) 0 (0)

Creatinine grade 2 (1.4-1.8x ULN), n (%) 0 (0) 1 (2) 1 (1)

Most common AEs (>10%), n (%) Fatigue Headache Diarrhea Pruritus Rash

21 (48) 6 (14) 3 (7)

5 (11) 6 (14)

12 (24) 6 (12) 5 (10) 0 (0) 2 (4)

33 (35) 12 (13)

8 (9) 5 (5) 8 (9)

Wedemeyer D , et al. 52nd EASL; Amsterdam, Netherlands; April 19-23, 2017. Abst. PS-159.

*SAEs all determined by the investigator to be “not drug related” : hospitalization for cervical spine disc herniation; hospitalization for chest pain; hospitalization for dizzinessl; pancreatitis without hospitalization; hospitalization for shoulder cyst surgery

C-SURGE Study:

Adverse Events

-25 0 25 50 75 100

No Treatment

Treat 12,000/year

Current Treatment,Target Cirrhosis

Treat 30,000/year

Current Treatment(25,200 per year)

% of Reduction in Prevalence 2015 to 2020

• Prevalence declining

slightly without

intervention

• Current treatment rate

(25,200 per year) will

lead to 87.1% (73.4 –

93%) reduction in

prevalence by the end

of 2020

• If treatment numbers

decline target will not be

reached

HCV Elimination in Georgia Study:

Impact on Prevalence

Walker J, et al. 52nd EASL; Amsterdam, Netherlands; April 19-23, 2017. Abst. PS-125

Summary

» New EASL HBV guidelines

» For HBV therapy TAF offers a new treatment option with

significant less potential for bone and renal toxicity.

» Of note 20% of all HCV infections globally are estimated to be

diagnosed in 2017. Under consideration of the 2030 goal of 90%

HCV infections diagnosed globally there still is a long way to

go.

» HCV treatment coverage worldwide is still below 10%

emphasizing the need of considerable HCV treatment scale-up

to reach the WHO 80% HCV treatment target in 2030.

» New pangenotypic regimens can be expected which will allow at

least for some combinations shorter treatment durations as well

as offer treatment options who have failed prior DAA therapy

and have 2-drug class resistance

Seite 42

Documents

EASL Highlights 2017regist2.virology-education.com/2017/13thCoinfection/06... · 2017. 7. 6. · EASL 2017 » WHO global hepatitis report » New EASL HBV guidelines » TDF TAF »