Achieving WHO Recommendations for HCV Elimination in the Eastern Mediterranean Region I. Waked April 12, 2016

WHO Eastern Mediterranean Region Population: ~600 Million Afghanistan Oman Bahrain Pakistan Djibouti Palestine Egypt Qatar Iran Saudi Arabia Iraq Somalia Jordan Sudan Kuwait Syria Lebanon Tunisia Libya UA Emirates Morocco Yemen Occupied Palestinian Territory

In 2016, there are approximately 15 In 2016, there are approximately 15.2 million viremic HCV infections in the Eastern Mediterranean region (2.4% prevalence) Prevalence (Viremic) Total Infected 250,000 6,000,000 0.0%-0.6% 0.6%-0.8% 0.8%-1.3% 1.3%-2.9% 2.9%-12.0% 25,000 Source: Polaris Observatory (http://www.polarisobservatory.com/)

In 2016, there are 15. 2M viremic infections, 2 In 2016, there are 15.2M viremic infections, 2.9M already diagnosed, 1.7M previously treated and 990K cured in the region Median Age: 45-49 yrs 20% The viremic prevalence of HCV in the Eastern Mediterranean region is 2.4% with nearly one fifth of infections already diagnosed. In 2016, an estimated 1.7M patients (or 11% of total infected) are treated. Source: Polaris Observatory (http://www.polarisobservatory.com/)

There is a wide range of prevalence, diagnosis and treatment rates across the Eastern Mediterranean region Bubble Diameter: HCV Prevalence 4% 2% 1% Source: Polaris Observatory (http://www.polarisobservatory.com/)

Two countries account for >80% of viremic HCV infections and treated patients 80% of Total Viremic HCV Infections (2015) 80% of Total Number Treated & Treatment Rate (Treatment Rate) Source: Polaris Observatory (http://www.polarisobservatory.com/)

The number of treated patients increased in 2015 after a period of warehousing patients Total Number Treated in Eastern Mediterranean Region Source: Polaris Observatory (http://www.polarisobservatory.com/)

Base 2014 Scenario – For comparison, the treatment paradigm in 2014 was extrapolated into the future Continue to treat with Peg IFN based therapies Most treatment is provided to patients with a fibrosis stage of ≥F1 Screening is continued each year to find new HCV cases 2014 2016 2017 2019 2021 2025 Treated 152,500 Newly Diagnosed 326,900 Fibrosis Stage ≥F1 New Infections 414,900 Treated Age 15-64 SVR 58% Source: Polaris Observatory (http://www.polarisobservatory.com/)

HCV infections will decline by 5%, while liver related deaths (LRD), HCC & decompensated cirrhosis (DC) will increase by 30-35%

Current 2015 Scenario – Extrapolate future treatment paradigm based on the current (2015) practice Switch to direct acting antivirals with higher SVR Keep the number of treated constant after 2015 Most treatment is provided to patients with a fibrosis stage of ≥F1 2014 2015 2016 2018 2020 2025 Treated 152,500 322,000 Newly Diagnosed 326,900 Fibrosis Stage ≥F1 New Infections 414,900 Treated Age 15-64 SVR 58% 86%

HCV infections will decline by 15%, while liver related deaths (LRD), HCC & decompensated cirrhosis (DC) will increase by 35% by 2030

After 2032, fewer than 145,000 individuals need to be treated annually WHO Scenario – Increase screening, treatment and eligibility to achieve a 90% reduction in new infections and a 65% reduction in LRD Switch to direct acting antivirals with higher SVR Increase treatment to achieve a >65% reduction in liver related deaths and a 90% reduction in new infections Expand screening to find infected individuals to treat Expand treatment to all patients (>=F0) Starting in 2017, expand treatment to up to 69 years of age 2014 2015 2017 2019 2021 2025 Treated 152,500 310,000 465,300 562,600 928,600 Newly Diagnosed 326,900 523,100 784,600 941,00 941,500 Fibrosis Stage ≥F1 ≥F0 New Infections 414,900 311,200 186,700 93,400 37,300 Treated Age 15-64 15-69 SVR 58% 86% 90% 95% After 2032, fewer than 145,000 individuals need to be treated annually

Start to run out of patients to treat HCV infections will decline 80% by 2030 and 95% by 2035, while LRD will decline 65% by 2030 and 90% by 2035 Start to run out of patients to treat

The 2016 prevalence is estimated to be 2% In 2016, there are an estimated 15 million HBsAg+ individuals in the Eastern Mediterranean region with data for 82% of the infected population HBsAg+ (Prevalence) <1.0% 1.0%-2.5% 2.5%-5.0% 5.0%-10.0% >10% Total Infected 200,000 1,000,000 4,000,000 The 2016 prevalence is estimated to be 2% Source: Polaris Observatory (www.polarisobservatory.com)

Eight countries accounted for 80% of all hepatitis B infections in the Eastern Mediterranean region HBsAg+ Individuals (2016) 80% of Total 73% % of infants receiving 3 doses of HBV vaccine (2014) 94% 88% 75% 99% 94% 62% 99% Source: Polaris Observatory (www.polarisobservatory.com)

In 2016, it is estimated that 12% of HBsAg+ individuals in the Eastern Mediterranean region are HBeAg+ HBeAg+ Prevalence (% of HBsAg+) <2.5% 2.5%-5.0% 5.0%-10.0% 10.0%-20.0% >20% Source: Polaris Observatory (www.polarisobservatory.com)

In 2016, it is estimated that 16% of HBsAg+ individuals in the region are anti-HDV+ Anti-HDV+ Prevalence (% of HBsAg+) <2.5% 2.5%-5.0% 5.0%-10.0% 10.0%-20.0% >20% Source: Polaris Observatory (www.polarisobservatory.com)

Pakistan and Egypt account for >80% of HCV infections in the region Conclusions: There are an estimated 15.2 million viremic HCV and 14.8 million HBV infections in the region Pakistan and Egypt account for >80% of HCV infections in the region Eight countries in the region account for 80% of HBV infections with Pakistan and Sudan leading It is feasible to eliminate HCV infections in the Eastern Mediterranean region region Programs to reduce new infections are critical to achieve elimination in the region - awareness campaigns, education of medical students/ community, adoption of single-use syringes, and programs for high risk populations (super injectors, dialysis patients, etc) Treatment has to be increased to 6-10% of total infections (coupled with active screening) Screening will become necessary as early as 2017 to ensure there are enough patients available for treatment