Prof. Gamal EsmatProf. Hepatology &Ex. Vice President of Cairo University, Egypt

Member of WHO Strategic Committee for Viral Hepatitis

www.gamalesmat.com

How to Treat HCV in a Resource-Limited Setting The Success Story in Egypt.

H EGYPT

▪ Estimated ~ 170 million globally

World Health Organization. Hepatitis C: global prevalence: update. 2003. Farci P, et al. Semin Liver Dis. 2000;20:103-126. Wasley A, et al. Semin Liver Dis. 2000;20:1-16.

>10%

~2-5%

~1-2%

Population: 96 Million

HCV-Ab prevalence:~7%

G4 about 90%

Global prevalence &genotype distribution

Trends in Percentage of population age 15-59 testing positive HCV Ab, Egypt

1996-2008-2015

22,920,1

25,8

14,211,8

16,6

10 9

12

total Women Men

Grafiektitel

1996 2008 2015

Ribavirin

Pegylatedinterferons

Suppression of HCV with DAA combination

(PI + NI)

Curability of HCV without

interferon

Frequent curability of

diverse populations without IFN

Simeprevir or sofosbuvir with IFN (GT1)

HCV therapy: past, present and

future

2015+1990 2000 2005 2010 2011 2012 2013 2014

InterferonProof

of concept for DAA (PI)

Telaprevir and

boceprevir

Daclatasvir(Japan and

Europe)

Daclatasvir+sofosbuvir (GT1b)

Ledipasvir + sofosbuvir

Paritaprevir/RTV/ombitasvir +

dasabuvir ± RBV

Simeprevir + sofosbuvir

First approved IFN-free therapy: Sofosbuvir +

RBV (GT2,3)

Simeprevir + sofosbuvir (off label use in US and

EU)

6–19 11–19 10–22

31–4433–36

61–79

18–3942–46

76–8266–79

80–9085–97

0

20

40

60

80

100

24 48 78

IFN monotherapy (weeks) IFN + ribavirin PegIFN PegIFN + ribavirinPegIFN + ribavirin + BOC/TVR SMV or SOF +PegIFN + RBV

SOF +RBV

All genotypes Genotype 1 Genotype 2/genotype 3

Evolution of HCV treatment and SVR

rates

Davis GL, et al. N Engl J Med 1989; 321:1501–1506; Poynard T, et al. N Engl J Med 1995; 332:1457–1462; McHutchison JG, et al.

N Engl J Med 1998; 339:1485–1492; Poynard T, et al. Lancet 1998; 352: 1426–1432; Zeuzem S, et al. N Engl J Med 2000;

343:1666–1672; Linsay KL, et al. Hepatology 2001; 34:395–403; Pockros PJ, et al. Am J Gastroenterol 2004; 99:1298–1305;

Manns MP, et al. Lancet 2001; 358:958–965; Fried MW, et al. N Engl J Med 2002; 347:975–982; Poordad F, et al. N Engl J Med 2011;

364:1195–1206; Jacobson IM, et al. N Engl J Med 2011; 364:2405–2416; Simeprevir prescribing information, November 2013;

Lawitz E, et al. N Engl J Med 2013; 368:1878–1887; Zeuzem S, et al. Hepatology 2013; 58(Suppl 1):733A; AbbVie press release

2014 [Accessed 25-02-14]; Gilead press release 2013 [Accessed 25-02-14]; Sulkowski MS, et al. N Engl J Med 2014; 370:211–221.

1989 2011 2013 2014/15

SV

R (

%)

DAA

comb

os

95–100

We now have highly efficacious DAAs that target

different stages in the HCV lifecycle

Lindenbach BD, Rice CM. Nature 2005;436(Suppl):933–8; Liang J, Ghany MG. N Engl J Med 2014;370:2043–7.

DAA: direct-acting antiviral agent; ER: endoplasmic reticulum; GT: genotype; IFN: interferon; LD: luminal domain; NA: nucleos(t)ide analogue;

NS: non-structural protein; SVR: sustained virological response

Receptor bindingand endocytosis

Fusion and uncoating

Transportand release

(+) RNATranslation andpolyprotein processing

RNA replication

Virionassembly

ER lumen

LD

LD

ER lumen

LD

NS3 protease

inhibitors

Non-NA NS5B inhibitors

NA NS5B inhibitors

NS5A inhibitors

Membranousweb

96%

SVR

Summary of New England Journal

of Medicine studies on IFN-free therapy

in GT 1 patients published in 2014

3680/

3826

Percentage of women and men with an active hepatitis C infection by age, Egypt 2015

0,9 1,5 1,93,2

5,3

7,3

10,4

16,117,6

0,6

3,1

4,7

7,1 6,9

10,8

12,4

23,7

27,8

0

5

10

15

20

25

30

15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59

women

men

Percentage of HCV infection with Anti Schistosomiasis treatment (2008-2015)

24,8

11,2

23,8

10,7

3,35,4

0

5

10

15

20

25

30

35

Had antiSchisto

treatment

No Do not know,missing

2008

2015

Females

31,3

15,5

10,9

16,9

4,42,1

0

5

10

15

20

25

30

35

Had antiSchisto

treatment

No Do not know,missing

2008

2015

Males

Opening of 23 national treatment centres, 2007-2013

Total number of patients treated with PEG-IFN (2007-2013): 350,000Annual number of new patients treated: 45,000Annual budget from the Ministry of Health: 90 million $

The course for 3 months will cost 900 $ instead of 84 000 $ in USA.

Manufactured outside Egypt but with different color(FDA approved) and written on it(to be sold only in Egypt).

Renewal of the agreement every year.

A large number of patients were ineligible for

treatment

Roche. PEGASYS (peginterferon alfa-2a) SmPC, October 2017 RBV: ribavirin

IFN-based therapy era

Chronic HCV-

infected patients

x Intolerant to IFN

x Intolerant to RBV

x Autoimmune conditions

x Hepatic dysfunction or

decompensated cirrhosis

x Severe heart disease

x Pregnant

x Mental health risk

Treatable HCV

patients

…and more patients are now eligible for

treatment

DAA therapy era

Chronic HCV-

infected patients

• Cirrhotic

• Co-morbidities

• Renal impairment

• Psychiatric

• Drug user

• Transplant

• Decompensated cirrhotic

Treatable HCV

patients

The number of treated patients in Egypt has

increased dramatically with the introduction

of DAAs

Polaris Observatory. Hepatitis C. Available at:

http://polarisobservatory.org/polaris_view/graphs.htm (accessed November 2017)

2012 2014 20162010

250,000

500,000

750,000

02008

Year

Nu

mb

er

of

pati

en

ts t

reate

d

Non-Nucs

NS5A inhibitors‘…asvirs’

Sofosbuvir Ledipasvir

Sofosbuvir Daclatasvir

SofosbuvirSimeprevir

Protease inhibitors‘…previrs’

Polymerase inhibitors‘…buvirs’

Nucleos(t)ide

Paritaprevir/r Ombitasvir

Sofosbuvir + RBV

IFN-free regimens

EASL Recommendations 2015, DOI: http://dx.doi.org/10.1016/j.jhep.2015.03.025. Accessed April 2015.

Our aim

to maintain a disease Control (by reaching international prevalence disease rates with 2%infection rate compared with the current 7% infection rate).

To reach for disease Elemination(disease rate <1%)

Waked,……,Esmat.et.al .Ar.J.G.2014

Elimination of HCV in EgyptOvercoming the Barriers

Decrease incidenceIdeal drug

Mass treatment

Elimination of HCV in EgyptOvercoming the Barriers

Decrease incidenceIdeal drug

Mass treatment

Decrease incidence

• Blood safety.

• Avoid unneeded injection.

• Auto destructive syringes.

• Infection control.

• Media awareness.

• Case detection and treatment by Ideal drug.

Can treatment impact HCV spread?

• Treatment can ba a method of prevention if:

• Applied early in the course of infection.

R0 of the untreated HCV epidemic in the Egyptian community is 3.50 (95% CI 2.95-4.03).

• Efficacy >80%

• Patients contributing most to HCV spread, the so-called«surperinjectors», are targeted preferentially (for treatment, and prevention!)

(Breban et al. Lancet Global Health, 2014)

National Plan of Action: conclusions

• Increase policymakers’ commitment to supporting the policy change necessary to prevent viral hepatitis transmission.

• Educate healthcare workers to prevent transmission of viral hepatitis in Egypt.

• Increase public awareness of viral hepatitis prevention.

• Promote safe injection practices in the community.

• Annual treatment of 200-350.000 patients by DAA.in 46 centers in 2015 aiming to reach 100 centers by the end of 2016

Egyptian National Plan of Action for the Preventton , Care & Treatment of Viral Hepatitis 2014–2018

Elimination of HCV in EgyptOvercoming the Barriers

Decrease incidenceIdeal drug

Mass treatment

DAAs Battle

National Victory Phase

Generics(15% of the brands)

Negotiation Phase

Brands(1% of its USA price)

25

Victory Phase

Egyptian Generics

26

The cost of 3 months treatment(sofo+dacla) per patientBrand vs Generic( 1$=17 EP)

EP 10.545

EP 1.527

0

2.000

4.000

6.000

8.000

10.000

12.000

Reduced by 85,5 %

SOF-DAC/RBV

600.000 Patients in 2016

Money Saved Over 12 Months(600.000 Patients)

600,000

patients

15%

5,359,200,000 EP

Availability of the generic drugs in a reduced price encourage people to take medication from private sector (300.000 patients)

80889160%

29321722%

20169415%

406943%

1,344,496 Patients

Govermental support

HIO

Cash

Military & Police hospitals

Number of treated patients through the Egyptian national treatment program with DAAs till the end of 2017

NCCVH registry

Availability of the generic drugs in a reduced price encourage people to take medication from private sector (300.000 patients)

Treatment outcome for the different Protocols (Real Life)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

SOF/IFN/RBV SOF/RBV SOF/SIM SOF/DAC SOF/DAC/RBV

90%

78%

93% 97% 96%

Perc

ent

A. Elsharkawy, R. Fouad, W. El Akel, M. El Raziky, M. Hassany, G. Shiha, M. Said, I. Motawea, T. El Demerdash, S. Seif, A. Gaballah, Y. El Shazly, M. A. M. Makhlouf, I. Waked, A. O. Abdelaziz, A. Yosry, M. El Serafy, M. Thursz, W. Doss, G. Esmat . Sofosbuvir-based treatment regimens: real life results of 14 409 chronic HCV genotype 4 patients in Egypt. Aliment Pharmacol Ther 2017; 45: 681–687

Rasha Eletreby | Wafaa Elakel | Mohamed Said | Mohamed El Kassas| Sameh Seif | Tamer Elbaz | Maissa El Raziky | Siham Abdel Rehim| Samy Zaky | Rabab Fouad | Hadeel Gamal Eldeen | Mahmoud Abdo | Mohamed Korany | Ayman Yosry | Magdy El Serafy | Manal Hamdy El-Sayed | Yehia ElShazly | Imam Waked| Wahid Doss| Gamal Esmat. Real life Egyptian experience of efficacy and safety of Simeprevir/ Sofosbuvir therapy in 6211 chronic HCV genotype IV infected patients. Liver International 2016; 1–8

Elimination of HCV in EgyptOvercoming the Barriers

Decrease incidenceIdeal drug

Mass treatment

1 6 4 3 29 8

Patients registered online for appointments till 1/6/2017

A web-based online registration system website (www.nccvh.org.eg) once the first DAA was registered in Egypt.This portal was designed for registration of patients with HCV and scheduling appointments at the treatment centres. Inputs from patients’ registry include their national ID, residence and a simple question for validation.

Online Regestiration

>150 Treatment centers affiliated to HCV National Treatment Program(NCCVH&HIO) in Egypt

In 2007, the NCCVH established its first specialized centresfor treatment of viral hepatitis within MOHP healthcare facilities. Centres were planned to be geographically distributed in the most populous areas. Training the healthcare professionals (hepatologists, infectious disease specialists, physicians ) to deliver an efficient counseling, care and treatment programme for patients with chronic HCV in accordance with the updated national guidelines.

El-Akel W, .., Esmat, Doss . National treatment programme of hepatitis C in Egypt: hepatitis C virus model of care. J Viral Hepat. 2017;00:1-6. doi:10.1111/jvh.12668.

Nile River in Cairo

Mass Treatment

Treatment with 90% curing rate or higher should be applied.

Number of yearly cured cases should exceed from 65,000 case in 2014 to 150,000 case in 2015(>300.000),

then to 275,000 case in 2016(>600.000), then to 350.000 from 2018.

To reach 2% Infection Rates in 2025 and less than 1% in 2030:

28/07/2016NO waiting lists

Timeline for treatment protocolsلقوميةأنظمة العالج المتبعة في الوحدات التابعة اللجنة ا

Dec

-14

Jan

-15

Feb

-15

Mar

-15

Ap

r-1

5

May

-15

Jun

-15

Jul-

15

Au

g-1

5

Sep

-15

Oct

-15

No

v-1

5

Dec

-15

Jan

-16

Feb

-16

Mar

-16

Ap

r-1

6

May

-16

Jun

-16

Jul-

16

Sof/IFN/RBV

SOF/RBV

SOF/SIM

SOF/DAC

SOF/DAC/RBV

Generic DAA

Where Egypt was (<2014)

IFN SVR

Waked I, et al. Arab J Gastroenterol 2014;15:45–52; National Registry, data on file IFN: interferon; SVR: sustained virological response

6,000,000 20% 30%50%

(3%)

Diagnosed

patients

HCV-infected

patients

Where Egypt is now (2017)

SVRDAADiagnosed

patients

HCV-infected

patients

6,000,000 20% 90–95%90–95%

(16%)

Waked I, et al. Arab J Gastroenterol 2014;15:45–52; National Registry, data on file DAA: direct-acting antiviral agent

Targeted screening for HCV in Egypt

• Families of HCV patients

• Healthcare providers

• Prisoners

• Students admitted to universities

• Patients attending intervention procedures in hospitals

• Before ID or driving license

• Government employees

• Everyone

Esmat G, personal opinion ID: identification document

• Launched in January 2017

• Screened 3,300,000 till August 2017

• Stakeholders

– MOH (preventive sector, NCCVH)

– Ministry of Administrative development

– National Bank

– NGO

Screening Program

Media&NGOs

Screening ProgramLaunched in January 2017

Screened 3,300,000 till August 2017

3,300,000 screened subjects

1,500,000

6 categories

1,800,000

Field screening

Saliva rapid testELISA test

•Upper Egypt•All age groups

•Inpatients•Health care workers•Prisoners•First year students•Submitted for travel•Blood banks Donors

Screening results till Aug 2017 3,300,000

HCV Ab +ve; 290400

HCV Ab -ve; 3009600

HCV RNA +ve86%

HCV RNA -

ve14%

249744 patients need to be treated

Current national treatment program centers

MOH 101 units

NCCVH 71 units

Total number 172 units

Where Egypt could go! (>2017)

SVRDAA

Slides with courtosy of Prof. H. Wedemeyer

Diagnosed

patients

Diagnosed

patientsDAA SVR

Waked I, et al. Arab J Gastroenterol 2014;15:45–52; National Registry, data on file

HCV-infected

patients

6,000,000 90–95% 90–95% 90–95%

Curing of 3,750,000 patients should be considered to reach 2% infection rates.

Curing of 5,000,000 patients to reach less than 1% infection rate, during selected

period of time.

Waked,……,Esmat.et.al .Ar.J.G.2014

Elimination of HCV in Egypt

HCV treatment in 2013 and strategies to reduce

the burden of HCV by 2030

Waked I, et al. Arab J Gastroenterol 2014;15:45–52

2013

2030

a) Increase

efficacy only

b) Increase

efficacy and treatment

Treated (annual) 65,000 65,000 325,000

Treatment rate 1.1% 1.1% 7.1%

Average SVR 48% 90% (2014) 90%

Newly diagnosed (annual)

125,000 125,000 340,500

Common treatment age 15–59 15–59 15–74

Treated stages ≥ F2 ≥ F2 ≥ F0

6.000.000

4.045.000

280.000

0

1.000.000

2.000.000

3.000.000

4.000.000

5.000.000

6.000.000

7.000.000

Total infected

-95%

630.000

507.000

76.000

0

200.000

400.000

600.000

800.000

Compensated cirrhosis

-88%

16.000 16.000

2.400

0

5.000

10.000

15.000

20.000

HCC

-85%

138.000

110.000

17.000

0

50.000

100.000

150.000

Decompensated cirrhosis

-87%

2013

201320132013

2030a 2030b

2030a 2030b2030a 2030b2030a 2030b

World Hepatitis Day in Egypt 28July 2015

• Egypt was chosen to host World Hepatitis Day 2015 as the country has demonstrated a high level of commitment by tackling hepatitis comprehensively in their plan of action for prevention, care and treatment.

• The Ministry of Health has set up 32 specialized centres and introduced a new hepatitis C drug last year, which is the first highly-effective and approved direct-acting antiviral drug for the nationwide treatment of hepatitis C infection. This medication is safer than previous medications and has been shown to cure more than 90% of those completing treatment, in combination with other drugs. In a global first, the drug has been made available to Egyptian patients for US$ 900, which is 1% of its international price. So far, 128 000 people have started the new treatment.

Number of deaths/year from selected conditions,Global Burden of Disease Study 2010 and 2013

Endorsement of success

.

Endorsement of success

From Land Of History

We will Make HCV a History

THANK YOUplease visit

www.gamalesmat.com

You can see this presentation and more