Access to HCV treatment in Egypt

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

Member of WHO Strategic Committee for Viral Hepatitis

www.gamalesmat.com

Global genotype distribution

Egyptian National Control Strategy for Viral Hepatitis

2008-2012April 2008

Arab Republic of Egypt, Ministry of Health and PopulationNational Committee for the Control of Viral Hepatitis

Objectives

National Survey

Availability of treatment

Awareness and Media Campaign

Infection Control

Research

National Survey 2008(DHS)

Population-level surveys to ascertain national

prevalence rates that can be broken down by age,

sex, and region

Household survey in 28 governorates.

Total of 12,780 women and men aged 15 – 59

consented to blood sampling.

ELISA test used to determine presence of antibodies.

Real time PCR testing for HCV RNA for all antibody

positive samples to detect active infections.

Prevalence of HCV in Egypt

Socioeconomic characteristicHCV antibody

positive, %

Urban-rural residence

Urban

Rural

10.3

18.0

Place of residence

Urban Governorates

Lower Egypt

UrbanRural

Upper Egypt

UrbanRural

Frontier Governorates

9.5

17.5

11.8

19.3

14.7

10.9

16.4

3.8

Education

No education

Some primary

Primary complete/some secondary

Secondary complete/higher

24.0

20.4

11.5

10.5

Wealth quintile

Lowest

Second

Middle

Fourth

Highest

18.6

17.1

16.4

11.6

10.2

Total 14.7

El-Zanaty F & Way A. Egypt Demographic & Health Survey 2008

2.75.5 4.6

10.2

13.3

21.223.6

27.1

35

5.5 4.4

8

13.1 14.3

24.6

35

49.3

43.5

0

5

10

15

20

25

30

35

40

45

50

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

HCV Egypt 2008

Women 2008 Men 2008

Overall Prevalence 14%

Total Number of HCV Positive Cases in 1996-2008

9,244,604

6,008,9935,839,102

4,379,326

0

1000000

2000000

3000000

4000000

5000000

6000000

7000000

8000000

9000000

10000000

all cases chronic HCV 1968

1996

2008

HCV AB HCV PCR

9.79.6

16.5

25.1

28.129.4 28.3

26.9

30.3

2.7

5.5 4.6

10.2

13.3

21.2

23.6

27.1

35

0

5

10

15

20

25

30

35

40

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

Women 1966 Women 2008

HCV Prevalence National Surveys 1996 vs 2008 Women 15-60 Ys

10.4 10.7

19.3

30.3

42.439.9 40.0 43.9

33.6

5.5 4.48

13.1 14.3

24.6

35

49.3

43.5

0

10

20

30

40

50

60

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

Men 1996 Men 2008

HCV Prevalence National Surveys 1996 vs 2008 Men 15-60 Ys

Egyptian Strategy for HCV Control

Nile River in Cairo

PEG INF Cost Per Course (MSF)

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 $

Response Rates of treated patients

0

10

20

30

40

50

60

70

80

90

EVR Week 24 respone

ETR SVR

88.5

6862

54

Perc

ent

Ministry of Health, EgyptMinistry of Health, Egypt

National Committee for Control of Viral Hepatitis

National HCV Treatment Program

National HCV treatment program: Positive outcomes

Governmental appreciation of the magnitude of HCV

problem in Egypt

National guidelines for treatment of chronic HCV

MOH and universities cooperation

Treatment for more than 350,000patients

>90% governmental funding

Data to answer a lot of questions

0

4,000,000

8,000,000

12,000,000

16,000,000

2013

2014

2015

2016

2017

2018

2019

2020

2021

2022

2023

2024

2025

2026

2027

2028

2029

2030

2031

2032

2033

2034

2035

2036

2037

2038

2039

2040

2041

2042

2043

2044

2045

2046

2047

2048

2049

2050

2051

2052

2053

2054

Current therapy 50% Efficacy, 50,000/yr Current therapy 50% Efficacy, 100,000/yr

DAA, 90% Efficacy, 250,000/yr

Number of Patients with Hepatitis C in EgyptCurrent Incidence (2.5/1000)

Annual mortality assumed at: 50/100,000 Or 5/1000 for HCV positive patients

0

4,000,000

8,000,000

12,000,000

16,000,000

2013

2014

2015

2016

2017

2018

2019

2020

2021

2022

2023

2024

2025

2026

2027

2028

2029

2030

2031

2032

2033

2034

2035

2036

2037

2038

2039

2040

2041

2042

2043

2044

2045

2046

2047

2048

2049

2050

2051

2052

2053

2054

Current therapy 50% Efficacy, 50,000/yr Current therapy 50% Efficacy, 100,000/yr

DAA, 90% Efficacy, 250,000/yr

Number of Patients with Hepatitis C in Egypt90% Reduction in Incidence (0.25/1000)

Annual mortality assumed at: 50/100,000 Or 5/1000 for HCV positive patients

HCV in EGYPTfrom Control to Elimination

To decrease HCV prevalence to< 2 % in Egypt

in 10 years(Mathematical modeling)

Effective treatment SVR > 90%

Annual treatment of 250.000 to 300.000 patients

Prioritize treatment early and to most frequent injectors

Elimination of HCV in EgyptOvercoming the Barriers

Ideal drug

Decrease incidence

Mass treatment

100

88

83

96100

87

9590.9

100 100 100

DCVPEG-RBV24-48 wks

SMVPEG-RBV

Experienced12+48 wks

SOFRBV

24-wksNaiive

LED SOF12 wks

PAR/r-OMBRBV

Naiive

ASV+BCV+DCV

% S

VR

12

Triple Therapy with PEG-RBV Interferon Free

1. Hezode C, et al. Gut, 2014 2. Moreno, C., et al. J Hepatol, 2014, 3. Lawitz, E., et al. N Engl J Med, 2013.

4. Ruane P et al. EASL 2014, 5. Esmat G el al. AASLD 2014, 6. Kapoor et al. AASLD 2014, 7. Pol S. et al. Hepatology 2014

Summary of Currently Available Therapies for HCV G4

IFN-Free Therapy in Genotype 4

• Randomized, open-label, multi-center study conducted in Egypt of the safety and efficacy of all-oral SOF + RBV in Egyptian patients with HCV GT 4, 103 patients

• SOF 400 mg + Weight-based RBV dosing

(1000-1200 mg).

• Male (67%), cirrhosis (17%), 52% high viral

load (>800,000 IU/ml), IL28B non-CC (81%).

Treatment-experienced

Week 0 12 24

SOF+ RBV (n=25)

SOF + RBV (n=24)

SOF+ RBV (n=27)

SOF + RBV (n=27)

Treatment-naive

Esmat G. et al. AASLD 2014,J.Hepatology,April,2015

77

90

0

20

40

60

80

100

12 wks 24 wks

Overall

8492

0

20

40

60

80

100

12 wks 24 wks

Naiive

70

89

0

20

40

60

80

100

12 wks 24 wks

Experienced

Naïve patients, with <=F2 Fibrosis, low viral load

(<600,000 IU): 100% SVR with 12 wks treatment

SOF + RBV in Treatment-Naïve and Experienced

Egyptian Patients

Agreement with Gilead

•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.

Ideal Drug

It is important for patients treatment but more important for control and eradication of any infectious disease

Elimination of HCV in EgyptOvercoming the Barriers

Ideal drug

Decrease incidence

Mass treatment

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.

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

Decrease incidence

•Blood safety.

•Avoid unneeded injection.

•Auto destructive syringes.

•Infection control.

•Media awareness.

•Case detection and treatment by Ideal drug

Quantifying Epidemic Severity in EgyptR0 theory

•R0: the expected number of secondary cases that an infected individual causes in a fully

susceptible population during their entire infectious period.

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

• The treat early strategy would be more effectivebecause it reduces transmission by timely treatment and decreases incidence..

34

High Injection Rate

•There is high heterogeneity in health care access in Egypt; 5% of the population takes more than 50% of all injections (2008 DHS).

•The epidemic is maintained by <5% of the population, consisting mostly of individuals with high injection rates.

• Prioritizing access to treatment early and by injection rate may be highly effective in reducing incidence.

Economic Burden of Hepatitis C in Egypt

• HCV infection is a huge economic burden in Egypt

– Direct healthcare cost EGP 3Bln

– Indirect economic impact of disability EGP 26Bln

– Intangible costs to society and families not assessed.

• Treatment of large numbers of patients with effective therapy is the only option for control

– Curing a patient saves EGP 50,000 for the next 15 years.

• Preventing a case saves EGP 120,000 for the next 40 years.

• One $ = 7.7 EGP.

Waked, NLI.

Elimination of HCV in EgyptOvercoming the Barriers

Ideal drug

Decrease incidence

Mass treatment

Mass TreatmentImproving Access to Therapy in Egypt

•Availability of other DAA in Egypt by a reduced price like sofosbuvir.

• Implementation of national program for HCV screening.

• Increasing the treatment centers to be more than 50 centers this year.

•Simplification of the treatment guidelines aiming for faster evaluation and less investigations.

•Extension of treatment to all HCV PCR positive patients .

•Raising fund from NGOs for evaluation and treatment of HCV patients.

38

National HCV Treatment Program

Real life experience

National Committee for Control of Viral Hepatitis

April 2015

No of patients registered on the NCCVH Portalsince 18 Sep 2014 till 28 Feb 2015

103258

51237 51701

0

20000

40000

60000

80000

100000

120000

18/09/2014 19/09/2014 20/09/2014

Registry in first 3 days of NCCVH portal

Week 4 viremia (n=7409)

negative viremia,

6782

positive viremia, 627

92%

Week 12 viremia (n=1958)ISVHLD 2015 ,P 149

negative viremia,

1919

positive viremia, 39

SVR of Triple Therapy

• In the multi-center national treatment program that started including patients in late October 2014, a total 21,318 patients(>F2) have started triple therapy with 12 weeks of SOF-PEG-RBV till June 2015. By the end of November 2014, 547 patients included, and have currently reached 12 weeks after the end of therapy.

• By end of treatment (week 12) 527 had HCV-RNA below level of quantification (15 IU.ml) (96.3%). Subsequently, 65 patients relapsed (11.9%), and by 12 weeks after end of treatment, 462 patients (84.5%) achieved SVR 12.

• Treatment experienced patients showed significantly lower SVR rate (153 of 194, 78.9%) compared to treatment naïve patients (309 of 353, 87.5%,OR 2.3, 95% CI 1.4-3.7 p<0.01)..

46

NCCVH HCV Treatment ProtocolUpdate, April 2015

Treatment will be available to all HCV PCR positive patients

Regimens will be categorized as follows:

IFN-based regimen:

• PegIFN alpha +Ribavirin (weight based; 1200 mg if ≥ 75 Kg or 1000 mg if < 75 Kg of body weight) +Sofosbuvir 400 mg/d for 12 weeks; basically received by INF-eligible patients

47

IFN-free regimens:

•Sofosbuvir 400 mg/d + Simeprevir 150 mg/d for 12 weeks. Basically received by IFN-ineligible patients.

•Sofosbuvir 400 mg/d + Ribavirin (weight based; 1200 mg if ≥ 75 Kg or 1000 mg if < 75 Kg of body weight) for 24 weeks received by organ transplant cases who have to receive specifically cyclosporine in their immunosupressiveregimenr or any other drugs contraindicated with semiprevir

48

Philippa Easterbrook, MD, FRCP, MPH

World Health Organization, Geneva

Geoff A. Beckett, PA-C, MPH

Centers for Disease Control and Prevention, Atlanta

15 June, 2015

Successes and opportunities• 82,000 on DAAs since September 2014

• Expansion from 26 to 32 treatment clinics

• High levels of commitment:

– National Committee

– Site clinical staff: High standards of medical clinic staff

– Clinics open until 6pm, three shifts, 6 days a week including during Ramadan.

• Achieved lowest negotiated drug costs worldwide.

• High profile treatment programme

• Well thought through (though complex) patient pathway

• Opportunity to develop a model for assessment of hepatitis treatment programmes

• National database with comprehensive dataset from largest patient population worldwide

Challenges and Threats

• Large and increasing patient volume requiring increased staff, space, clinics.

• Lack/loss of prioritisation of those with advanced disease

– Decompensated excluded

– Inequity in treatment access by geographic region

• No programmatic analysis of national database using key performance indicators along cascade of care, or feedback to sites.

• Delays in data entry:

– Requirement for live data entry; slow internet; Only 3 ports linked to server.

– Insufficient data entry staff and obstacles to recruitment

• Sub-optimal staging of liver disease:

– Discontinued Fibroscan; Fib-4 sub-optimal staging of liver disease.

– No routine clinical examination

• Multiple changes to protocols since start of programme.

• Multiple steps in patient pathway:

• Uncertainty over level of private prescribing of sofosbuvir and data capture

Conclusion

We are looking to say Goodbye Interferon

The ideal drug for treatment of HCV will be soon

within our reach.

( oral, short duration, SVR >90% , minimal side

effects and affordable)

•The ideal drug has an important role in prevention.