SALUD PREVENTIVA

DDA´S PARADIGM IN HCV TREATMENT

VIROLOGY EDUCATION SAN JUAN, PUERTO RICO

Dr. David KershenobichDirector General

Eradication: Incidence zero of HCV infection and decrease in cirrhosis and hepatocarcinoma. The concept of eradication is to eliminate HCV of the earth.

Andres Marco Rev Enf Emerg 2015

Control:Decrease the incidence of cirrhosisand hepatocarcinoma, as well as theincidence of HCV.

Elimination:Incidence zero in HCV infection and decrease of cirrhosis andhepatocarcinoma in a given area. The concept of elimination refersto the disappearance of the virus in an area, region, state orcountry

Worldwide prevalence of hepatitis C

3

71million

0.6%

The Polaris Observatory HCV Collaborators, Lancet Gastroenterol Hepatol 2017; 2: 161–76

Viral Hepatitis in the Americas

Data from GlobalBurden of Disease, 2016

Cooke et al. Lancet Gastroenterol Hepatol 2019; 4: 135–84

Prevalence of Anti-HCVin the Americas

Petruzziello et al. World J Gastroenterol 2016; 22(34): 7824-7840

BMC Med. 2014; 12: 145.

Liver Cirrhosis Mortality

• HCV is implicated in:

México

Cases of liver cirrhosis

Cases of hepatocarcinoma

Lozano R et al

Global Burden of Disease Study 2010

Lancet 2012;389:2095-128

¿Do we have an adequate drugto treat hepatitis C ?

Mangia A, et al. AASLD 2018; Poster #600

Genotype Fibrosis

1299/1319

RV

S12 (

%)

547/558

509/512

198/204

44/44

334/335

274/281

Efficacy of SOF/VEL for 12 weeksin real life

Efficacy of GLE/PIB for 8 o 12 weeksin real life

Wiegand J, et al. AASLD 2018; Poster #611

Genotype Fibrosis

592/609

RV

S1

2 (

%)

319/327

37/38

192/199

30/31

14/14

134/137

59/59

19/20

Pangenotypic Treatments for Hepatitis C

• SOF + DCV is licensed in the EU for the treatment of GT 1, 3 and 4, not GT 2, 5 and 6, chronic HCV infection. GLE/PIB for 16 weeks, not 12 weeks, is licensed in the EU for the treatment of GT 3 patients with prior PEG-IFN ± RBV ± SOF experience. Recommendations for people aged ≥18 years. aPeople with GT 3 infection who have received IFN and/or RBV in the past should be treated for 16 weeks; bSOF + DCV for 12 weeks may be considered in countries where genotype distribution is known and GT 3 prevalence is <5%; c12 weeks recommended for GT 3 patients with prior PEG-IFN ± RBV ± SOF experience; d12 weeks recommended for GT 3 patients with prior PEG-IFN ± RBV ± SOF experience; eIn GT 3 patients with cirrhosis where the Y93H RAS cannot be confirmed as absent, addition of RBV or treating with SOF/VEL/VOX recommended. DCV: daclatasvir; GLE: glecaprevir; GT: genotype; IFN: interferon; PEG-IFN: pegylated interferon; PIB: pibrentasvir; RAS: resistance associated substitution; RBV: ribavirin; SOF: sofosbuvir; VEL: velpatasvir; VOX: voxilaprevir

• WHO. Guidelines for the care and treatment of persons diagnosed with chronic hepatitis C virus infection. July 2018. Available at: http://apps.who.int/iris/bitstream/handle/10665/273174/9789241550345-eng.pdf?ua=1; EASL. J Hepatol 2018;69:461–511;

GLE/PIB SOF/VEL SOF + DCV

No cirrhosis Cirrhosis No cirrhosis Cirrhosis No cirrhosis Cirrhosis

8 weeks

16 weeks

12 weeks

16 weeks12 weeks 12 weeks

12 weeks

24 weeks

8 weeks

12 weeks

12 weeks

16 weeks12 weeks ± RBV — —

Requerimientos de los agentes antivirales de acción directa (AAD)

• Adapted from: Asselah T, et al. Liver Int 2018;38:7–13

ESSENTIAL FOR

EACH PATIENT

CRITICAL FOR

ELIMINATION

DELIVERY OF DAA`S

RVS >95%

Security

Tolerability

Pangenotypic

High resistance barrier

Short duration

Minimal pharmacological interactions

Less tablets

Treatment

High priority

Secondary

priorities

SVR

van der Meer AJ, et al. JAMA. 2012;308(24):2584-2593.

(%)

Hepatocellular carcinoma

Time in years

p<0.001

N=530 Without SVRl

With SVR

(%)Mortality related to the liver or liver transplantation

Time in years

p<0.001

N=530 Without SVR

With SVR

¿Do we have an adequate drugto treat hepatitis C?

yes

Searching for the missing patients

¿Are we prepared to carry out the diagnosis?

Only 14% of people with Hepatitis C in Latin America have been diagnosed and < 1% has received an adequate treatment

Point-of-care testing: Advantages

• Rapid testing.

• Allows testing and getting the result in the same visit.

• Can be done outside the clinical laboratories.

• Can be interpreted by non-specialists.

• Increases the number of patients tested andsimplifies the process of confirmation and referenceto treatment.

Point-of-care testing for hepatitis C

• Sensibility 95-99%

• Specificity 99-100%

• Results available in 5-10 minutes

• Easy to interpretJ Virol Methods 2018

FROM A TREATMENT STRATEGY TO THE ELIMINATION OF HEPATITIS C

Global Elimination of Hepatitis C

Lazarus J, et al. J Hepatol 2017;67:665–6

20

Industry

Direct antiviral

agents

Health

professionals

WHO

Legislators

Civil Society

Researchers

Elimination of HCV

Grebely J. EASL monothematic conference 2018; Oral #205020; Courtesy of the Kirby Institute, Sydney, Australia.

21

¿HOW?

¿With what?

Pangenotypic

simple therapy

¿Who?

Expand number of

treating physicians

¿Where?

Increase number of

treating centers

¿Regulations?

Simplification

Elimination of HCV by 2030

Global Health Sector Strategy on Viral Hepatitis, 2016 - 2021

22

Diagnosis of HCV

Treatment of VHC

20 400 60 80 100

(%)

2015 Basal

2030 Goals

90%

80%

Care Cascade for Hepatitis C patients

Yehia BR, et al. PLoS One 2014;9:e101554; WHO. Global health sector strategy on viral Hepatitis 2016–2021. Available at: http://apps.who.int/iris/bitstream/10665/246177/1/WHO-HIV-2016.06-eng.pdf?ua=1 (accessed March 2018)

23

100

0

20

40

60

80P

erc

en

tag

e

HC

V-P

AT

IEN

TS

Dia

gn

ose

d

Access

to

ca

re

TX SVR

Epidemiology of Hepatitis C in Latinamerica

Polaris Cascate 2017: Brazil, Mexico, Chile, Colombia and Argentina

1.905.300

442.000

27.200 80.000

Prevalence Diagnosed patients Treated patients in 2015 Patients treated by 2017

24

Yehia BR, et al. PLoS One 2014;9:e101554; WHO. Global health sector strategy on viral Hepatitis 2016–2021. Available at: http://apps.who.int/iris/bitstream/10665/246177/1/WHO-HIV-2016.06-eng.pdf?ua=1 (accessed March 2018)

25

HCV continuum of care

100

0

20

40

60

80H

CV

PA

TIE

NT

S

Dia

gn

ose

d

Acce

sto

cre

TXSVR

90 % reduction of new infections

90 % of diagnosed patients

80% elegible for treatment

Dia

gn

ose

d

Care Cascade for Hepatitis C patients

Pe

rce

nta

ge

Micro-elimination Strategies

• Lazarus J, et al. J Hepatol 2017;67:665–6

• More realistic objectives and goals. • Can be achived in a shorter period of time. • Tailored strategies. • Costs can be predicted. • Prevention of re-infections.

Models of Micro-Elimination in high riskpopulations

• Drug users

HIV/HCV co-infection

Migrants

Hospitals

Prisoners

Hemophilia

Men having sex with men

Transplanted patients

Cities

Dialysis

Chronic liver disease

Number of tablets (excluding RBV)

• Gilead Sciences Europe Ltd. VOSEVI® (sofosbuvir/velpatasvir/voxilaprevir) SmPC, December 2018; Gilead Sciences Europe Ltd. EPCLUSA ® (sofosbuvir/velpatasvir) SmPC, December 2018; Merck Sharp & Dohme Ltd. ZEPATIER ® (grazoprevir/elbasvir) SmPC, June 2018; Gilead Sciences Europe Ltd. HARVONI ® (ledipasvir/sofosbuvir) SmPC, December 2018; Bristol-Myers Squibb Pharma EEIG. DAKLINZA ® (daclatasvir) SmPC, July 2018; AbbVie Ltd. MAVIRET ® (glecaprevir/pibrentasvir) SmPC, July 2018; AbbVie Ltd. EXVIERA ® (dasabuvir) SmPC, October 2018; AbbVie Ltd. VIEKIRAX ® (ombitasvir/paritaprevir/ritonavir) SmPC, September 2018.

• This comparison is for illustrative purposes only. Minimum and maximum number of pills have been calculated based on treatment durations recommended on the posologytable in the respective SmPCs. DAA-naïve patients without or with compensated cirrhosis.

• DCV: daclatasvir; DSV: dasabuvir; EBR: elbasvir; GRZ: grazoprevir; LDV: ledipasvir; OBV: ombitasvir; PTV; paritaprevir; r: ritonavir; RBV: ribavirin

5684 84

56

168 168 168

84 84112

168

336 336

672

0

175

350

525

700

SOF/VEL/VOX SOF/VEL EBR/GRZ LDV/SOF SOF + DCV GLE/PIB OBV/PTV/r ± DSV

Min Max

With

foodWith

food

With or

without

food

With or

without

food

With or

without

food

With or

without

food

With

food

Road to Simplicity

PATIENT

PHYSICIAN

ONE TABLET A DAY FOR 12 WEEKS

12 WEEKS DURATION OF TREATMENT FOR

ALL CASES

Treatment easy to explain and prescribe

Hepatitis C

Think globally

Act locallySimplify Transform

FROM A TREATMENT STRATEGY TO THE ELIMINATION OF HEPATITIS C

CONCLUSIONS

PARADIGM 1: It is possible to go from a treatment strategy to an elimination strategy of Hepatitis C.

PARADIGM 2: Think globally and act locally.

PARADIGM 3: The model of care of Hepatitis C most be transformed and simplified.

PARADIGM 4: We need an integral model of care for Hepatitis C.

FROM CURE TO ELIMINATIONOF HEPATITIS C