Access to HCV treatment in Egypt Prof. Gamal Esmat Prof. 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 2008-2012 April 2008 Arab Republic of Egypt, Ministry of Health and Population National 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 characteristic Urban-rural residence Urban Rural Place of residence Urban Governorates Lower Egypt Urban Rural Upper Egypt Urban Rural Frontier Governorates Education No education Some primary Primary complete/some secondary Secondary complete/higher Wealth quintile Lowest Second Middle Fourth Highest HCV antibody positive, % 10.3 18.0 9.5 17.5 11.8 19.3 14.7 10.9 16.4 3.8 24.0 20.4 11.5 10.5 18.6 17.1 16.4 11.6 10.2 Total 14.7 El-Zanaty F & Way A. Egypt Demographic & Health Survey 2008
50 45 40 35 30 25 20 15 10 5 0 2.7 5.5 5.5 4.6 4.4 HCV Egypt 2008 Overall Prevalence 14% 8 10.2 13.1 13.3 14.3 21.2 24.6 49.3 35 27.1 23.6 35 43.5 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 Women 2008 Men 2008
Total Number of HCV Positive Cases in 1996-2008 10000000 9000000 8000000 7000000 6000000 5000000 4000000 3000000 2000000 1000000 0 9,244,604 5,839,102 6,008,993 4,379,326 HCV all cases AB chronic HCV HCV PCR1968 1996 2008
40 HCV Prevalence National Surveys 1996 vs 2008 Women 15-60 Ys 35 Women 1966 Women 2008 35 30 25 25.1 28.1 29.4 28.3 21.2 23.6 27.1 26.9 30.3 20 15 16.5 13.3 10 9.7 9.6 10.2 5 2.7 5.5 4.6 0 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59
60 50 HCV Prevalence National Surveys 1996 vs 2008 Men 15-60 Ys Men 1996 Men 2008 49.3 42.4 39.9 40.0 43.9 43.5 40 30.3 35 33.6 30 19.3 24.6 20 10 10.4 10.7 5.5 4.4 8 13.1 14.3 0 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59
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): 350,000 Annual number of new patients treated: 45,000 Annual budget from the Ministry of Health: 90 million $
Percent Ministry of Health, Egypt National Committee for Control of Viral Hepatitis National HCV Treatment Program Response Rates of treated patients 90 80 70 60 50 40 30 20 10 0 88.5 68 62 54 EVR Week 24 respone ETR SVR
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
Number of Patients with Hepatitis C in Egypt Current Incidence (2.5/1000) 16,000,000 12,000,000 8,000,000 4,000,000 0 2038 2039 2040 2041 2042 2043 2044 2045 2046 2047 2048 2049 2050 2051 2052 2053 2054 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 Current therapy 50% Efficacy, 50,000/yr Current therapy 50% Efficacy, 100,000/yr DAA, 90% Efficacy, 250,000/yr Annual mortality assumed at: 50/100,000 Or 5/1000 for HCV positive patients
Number of Patients with Hepatitis C in Egypt 90% Reduction in Incidence (0.25/1000) 16,000,000 12,000,000 8,000,000 4,000,000 0 2038 2039 2040 2041 2042 2043 2044 2045 2046 2047 2048 2049 2050 2051 2052 2053 2054 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 Current therapy 50% Efficacy, 50,000/yr Current therapy 50% Efficacy, 100,000/yr DAA, 90% Efficacy, 250,000/yr Annual mortality assumed at: 50/100,000 Or 5/1000 for HCV positive patients
HCV in EGYPT from 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 Egypt Overcoming the Barriers Ideal drug Decrease incidence Mass treatment
% SVR 12 Summary of Currently Available Therapies for HCV G4 Triple Therapy with PEG-RBV Interferon Free 100 88 83 96 100 87 95 90.9 100 100 100 DCV PEG-RBV 24-48 wks SMV PEG-RBV Experienced 12+48 wks SOF RBV 24-wks Naiive LED SOF 12 wks PAR/r-OMB RBV Naiive ASV+BCV+DCV 1. He zode 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
Esmat G. et al. AASLD 2014,J.Hepatology,April,2015 IFN-Free Therapy in Genotype 4 SOF + RBV in Treatment-Naïve and Experienced Egyptian Patients Naiive 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 Treatmentexperienced Treatmentnaive SOF+ RBV (n=25) SOF+ RBV (n=27) SOF + RBV (n=24) SOF + RBV (n=27) Week 0 12 24 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%). 100 80 60 40 20 0 Overall 77 90 12 wks 24 wks 100 80 60 40 20 0 100 80 60 40 84 92 12 wks 24 wks Experienced 70 89 Naïve patients, with <=F2 Fibrosis, low viral load (<600,000 IU): 100% SVR with 12 wks treatment 20 0 12 wks 24 wks
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 Egypt Overcoming 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 Egypt R0 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 effective because it reduces transmission by timely treatment and decreases incidence..
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 Egypt Overcoming the Barriers Ideal drug Decrease incidence Mass treatment
Mass Treatment Improving 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.
National HCV Treatment Program Real life experience National Committee for Control of Viral Hepatitis April 2015
No of patients registered on the NCCVH Portal since 18 Sep 2014 till 28 Feb 2015
Registry in first 3 days of NCCVH portal 120000 100000 103258 80000 60000 40000 51237 51701 20000 0 18/09/2014 19/09/2014 20/09/2014
Week 4 viremia (n=7409) positive viremia, 627 negative viremia, 6782 92%
Week 12 viremia (n=1958) ISVHLD 2015,P 149 positive viremia, 39 negative viremia, 1919
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)..
NCCVH HCV Treatment Protocol Update, 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
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 immunosupressive regimenr or any other drugs contraindicated with semiprevir
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.