Towards HCV Elimination in Egypt by 2020

Prof. Gamal Esmat Prof. Hepatology &Ex. Vice President of Cairo University, Egypt Member of WHO Strategic Committee for Viral Hepatitis www.gamalesmat.com Elimination

• Vision “A world where viral hepatitis transmission is stopped and everyone has access to safe, affordable and effective treatment and care”

• Elimination as a public health issue of concern - remove sustained transmission, remove hepatitis as a leading cause of mortality: – Elimination and not eradication: long wave of prevalence will remain for decades Global prevalence &genotype distribution Geographic HCV prevalence 1996

Alexandria 5.9% (95% CI: 4.2-7.7)

Cairo 8.2% (95% CI: 6.7-9.8) L Lower Egypt I 28.4% B (95% CI: 27.1-29.2) Y A Middle Egypt Red 26.5% Sea (95% CI: 23.7-29.4)

Upper Egypt 19.4% (95% CI: 17.2-21.6)

EGYPT Frank et al., (2000) SUDAN Trends in Percentage of population age 15-59 testing positive HCV Ab, Egypt 1996-2008-2015 Chart Title 1996 2008 2015

25.8 22.9 20.1 16.6 14.2 11.8 12 10 9

total Women Men 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 Phase 1 Interferon Treatment for some Opening of 23 national treatment centres, 2007-2013

Total number of patients treated with PEG-IFN (2007-2013): 350,000 Annual number of new patients treated: 45,000 Annual budget from the Ministry of Health: 90 million $ Better understanding of therapeutic targets Phase 2 DAA Treatment for All

• 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 The number of treated patients in Egypt has increased dramatically with the introduction of DAAs

750,000

500,000

250,000 Number Number of patients treated 0 2008 2010 2012 2014 2016 Year

Polaris Observatory. Hepatitis C. Available at: http://polarisobservatory.org/polaris_view/graphs.htm (accessed November 2017) DAAs Battle

Negotiation Phase Brands(1% of its USA price)

National Victory Phase Generics(15% of the brands)

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

12,000 EP 10.545 10,000

8,000 Reduced by 85,5 %

6,000

4,000

2,000 EP 1.527 0 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) 28/07/2016 NO waiting lists

Study Design

Non-Cirrhotic Treatment Follow-up IFN Naïve RDV+SOF n=45 SVR4 SVR12 SVR24 Group 1a n=90 RDV+SOF+RBV n=45 SVR4 SVR12 SVR24

IFN- RDV+SOF n=40 SVR4 SVR12 SVR24 Group 2 Experienced n=80 RDV+SOF+RBV n=40 SVR4 SVR12 SVR24 Cirrhotic Treatment Follow-up

IFN Naïve RDV+SOF n=31 SVR4 SVR12 SVR24 Group 1b n=60 RDV+SOF+RBV n=29 SVR4 SVR12 SVR24

IFN- RDV+SOF+RBV n=35 SVR4 SVR12 SVR24 Group 3 Experienced n=70 RDV+SOF+RBV n=35 SVR4 SVR12 SVR24

Time (weeks) 0 12 16 20 24 28 36 40

 Total patients enrolled = 300, all patients completed treatment evaluations as of the data cutoff for this report  High percentage of cirrhotic patients: 130/300 (43.3%) SVR12 Outcomes in Non-Cirrhotic Patients (ITT) 100% 100% 100 98% 95%

60 Group 1a Group 2

40 Percent of Patients of Percent

% % % %

2.0 0

0 0 0 0 0 Treatment Naive IFN Experienced RDV+SOF RDV+SOF+RBV RDV+SOF RDV+SOF+RBV SVR12 Discontinuation Relapse

 Among the 170 non-cirrhotic patients enrolled, there were three early discontinuations unrelated to safety or efficacy failure, WITH NO RELAPSES  100% SVR12 in non-cirrhotic patients , excluding discontinuations SVR12 Outcomes in Cirrhotic Patients (ITT) 100 100% 93% 92% 86% 80

60 Group 1b Group 3

.% Percent of Patients of Percent

20 %

% %

10.5

4 4

% % %

3.5

0 0 0 0 Treatment Naive IFN Experienced RDV+SOF RDV+SOF+RBV RDV+SOF+RBV 12 Wk RDV+SOF+RBV 16 Wk SVR12 Discontinuation Relapse  Among the 130 cirrhotic patients enrolled, there were two premature discontinuations (one safety related) and 6 virologic relapses  No relapses to date in the cirrhotic 16 week treatment cohort  Per protocol evaluation results in 94% SVR12 in cirrhotic patients WHO adds ravidasvir to HCV recommendation guidelines August 9, 2018

• The World Health Organization has added ravidasvir as a future pangenotypic direct-acting antiviral to the list of recommended therapies in their Guidelines for the Care and Treatment of Persons Diagnosed with Chronic Hepatitis C • Previously, ravidasvir has demonstrated high sustained virologic response rates in combination with other approved DAA regimens. • One study of combined ravidasvir with Sovaldi (sofosbuvir, Gilead Sciences) among Egyptian patients had an overall SVR rate of 98%. Where Egypt was (<2014)

HCV-infected Diagnosed IFN SVR patients patients

50% 6,000,000 20% 30% (3%)

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

HCV-infected Diagnosed DAA SVR patients patients

90–95% 6,000,000 20% 90–95% (16%)

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

Treatment outcome for the different Protocols (Real Life)

97% 96% 100% 90% 93% 90% 78% 80% 70% 60% 50%

Percent 40% 30% 20% 10% 0% SOF/IFN/RBV SOF/RBV SOF/SIM SOF/DAC SOF/DAC/RBV

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

• Families of HCV patients • Healthcare providers • Prisoners • Students admitted to universities • Patients attending intervention procedures in hospitals

Esmat G, personal opinion ID: identification document Screening Program Launched in August 2016 Screened 3,300,000 till August 2017

1,500,000 3,300,000 6 categories screened subjects 1,800,000 •Inpatients •Health care workers Field screening •Prisoners •First year students •Upper Egypt •Submitted for travel •All age groups •Blood banks Donors ELISA test Saliva rapid test Screening results till Aug 2017 3,300,000

HCV Ab +ve, 290400 HCV Ab -ve, HCV RNA - 3009600 ve 14%

HCV RNA +ve 86%

249744 patients need to be treated 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 Egypt

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 Total number of treated patients in Egypt 2,005,000patients 25000 45000 1% 2% 350000 18% governmental support 1100000 HIO 55% 485000 private *Police & Army forces 24% Presidential initiative

Before mass screening initiative in 1st Oct 2018 Where Egypt could go! (>2018)

HCV-infected DiagnosedDiagnosed DAADAA SVRSVR patients patientspatients

6,000,000 90–95% 90–95% 90–95%

Waked I, et al. Arab J Gastroenterol 2014;15:45–52; National Registry, data on file Slides with courtosy of Prof. H. Wedemeyer Phase 4 Screening for All People treated so far have mostly been those living with the diagnosis, and a few hundred thousand who were identified through screening programs over the past year.

Epidemiological studies show that, in addition to those who have already been treated, there are 3–4 million individuals with undiagnosed HCV infection in Egypt.

This pool of undiagnosed individuals, if untreated, is at risk of progressive disease and is a potential source of infection over the coming years.

www.thelancet.com/gastrohep Vol 3 October 2018 On July 29, 2018,

Egypt embarked on the largest disease screening campaign in history. By September, 2019, the Ministry, through the NCCVH, will screen all adults aged 18 years and older in Egypt (currently a population of 59 million, targeting 52 million individuals after exclusion of those who have been treated or screened before). Screening will include testing for HCV antibodies, and assessment for hypertension, diabetes, and obesity.

www.thelancet.com/gastrohep Vol 3 October 2018 Campaign Phases and Governorates Distribution

Phase Time frame Boarder Gov. Lower Egypt Urban Gov. Upper Egypt South Sinai Damietta Port Said Fayoum October- One Behira December 2018 Matrouh Alexandria Asuit Qalubia North Sinai Kafr Elsheikh Cairo Sohag December 2018- Ismailia Beni Swif Two February 2019 Red Sea Menofia Luxor Swiss Aswan Gharbia Menia March- April Three New Valley Shariqa Giza 2019 Qena Dakahlia 26.85 مليون مواطن من بداية الحملة

27 • Million citizens from 1/10/2018 to 15/1 /2019 • Team component Medical member (Physician, pharmacist dentist)

39 Nurse and IT Specialist

نتائج المرحلة األولى

43 نسبة تحقيق المستهدف الكلي بين محافظات المرحلة األولى

نسبة تحقيق المستهدف الكلي 85% 85% 77% 76% 72% 71% 71% 62% 59%

متوسط تحقيق المستهدف الكلي بين محافظات المرحلة األولى = 75 % 44 نسب اإلصابة بفيروس سي بين محافظات المرحلة األولى

نسبة اإلصابة فيروس سي 6% 5% 4% 4% 3% 3% 3% 2% 2%

متوسط اإلصابة بفيروس سي بين محافظات المرحلة األولى = 4 % 45 نسبة ارتفاع السكر العشوائي بالدم عن 200 ملجم / دل بين محافظات المرحلة األولى

نسبة ارتفاع السكر بالدم عن 200 6% 5% 5% 5% 4% 4% 4% 3% 3%

متوسط ارتفاع السكر بالدم بين محافظات المرحلة األولى = 4 % 46 نسبة ارتفاع ضغط الدم عن 90/140 مل زئبق بين محافظات المرحلة األولى

نسبة ارتفاع ضغط الدم 30% 27% 24% 21% 21% 19% 17% 16% 16%

متوسط ارتفاع ضغط الدم عن 90/140 مل زئبق بين محافظات المرحلة األولى = 21 %

47 نسبة اإلصابة بالسمنة بين محافظات المرحلة األولى

نسبة اإلصابة بالسمنة بين محافظات المرحلة األولى 47% 46% 42% 38% 38% 31% 31% 31% 26%

متوسط اإلصابة بالسمنة بين محافظات المرحلة األولى = 37 %

48 Flow of patients in screening initiative

HCV AB PCR -ve -ve

All HCV AB PCR Lab tests PCR +ve Treatment screened +ve testing + /- US

شبكة ربط وحدات العالج Source Registration HCV treatment Units وحدات العالج موقع الحجز 49 Total number *registered on nccvh.org.eg Since 1st October 2018 till 15 Jan 2019

1000000 900000 866768 800000 700000 600000 553347 500000 400000 345903 300000 200000 100000 0 Till 24 Nov 2018 Mid Dec 2018 Mid Jan 2019 *Automated registration from screening sites (first & second phase) 50 نتائج المرحلة الثانية حتى 13 فبراير2019

51 تحقيق المستهدف الكلي

نسبة تحقيق المستهدف الكلي بين محافظات المرحلة الثانية 91% 86% 87% 76% 76% 72% 74% 75% 66% 68%

47%

متوسط تحقيق المستهدف بين محافظات المرحلة الثانية = %78

52 نسب اإلصابة بفيروس سي بين محافظات المرحلة الثانية

نسبة اإلصابة فيروس سي بين محافظات المرحلة الثانية 8% 8%

5% 4% 4% 4% 3% 3% 3% 2% 2%

متوسط اإلصابة بفيروس سي بين محافظات المرحلة الثانية = 4 %

53 HCV treatment in 2013 and strategies to reduce the burden of HCV by 2020

2020 Total infected 2013 a) Increase b) Increase efficacy efficacy and 7,000,000 6,000,000 only treatment 6,000,000 5,000,000 Treated (annual) 65,000 65,000 325,000 4,045,000 4,000,000 Treatment rate 1.1% 1.1% 7.1% 3,000,000 Average SVR 48% 90% (2014) 90% 2,000,000 -95% Newly diagnosed 1,000,000 125,000 125,000 340,500 280,000 (annual) 0 Common treatment age 15–59 15–59 15–74 2013 2030a 2030b Treated stages ≥ F2 ≥ F2 ≥ F0 Compensated Decompensated cirrhosis cirrhosis HCC 800,000 138,000 630,000 150,000 20,000 16,000 16,000 110,000 600,000 507,000 15,000 100,000 400,000 -87% 10,000 -85% -88% 50,000 17,000 5,000 2,400 200,000 76,000 0 0 0 2013 2030a 2030b 2013 2030a 2030b 2013 2030a 2030b

Waked I, et al. Arab J Gastroenterol 2014;15:45–52 Number of deaths/year from selected conditions, Global Burden of Disease Study 2010 and 2013

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