the burden of disease related to obesity H. Razavi, PhD, MBA July - PowerPoint PPT Presentation

The value proposition of NASH therapy on the burden of disease related to obesity H. Razavi, PhD, MBA July 5, 2018 homie.razavi@centerforda.com

Dis isclosure: The epidemiology / modeling work was funded through a multi-sponsored research grant from Gilead, Intercept, and Boehringer Ingelheim. The funders had no influence over the design, the implementation, or the outcomes of the study. The economic impact analysis was funded by CDA. H. Razavi has not received any personal remuneration for this or any other project.

This work would not be possible wit ithout th the in inputs of f th the following exp xperts: • China – Wei L • France – Ratziu V • Germany – Bantel H, Geier A, Kroy D, Manns M, Schattenberg JM, Tacke F, Trautwein C & Zeuzem S • Italy – Bellentani S, Colombo M, Craxi A, Kondili L, Marchesini G & Petta S • Japan – Eguchi Y, Nakajima A, & Tanaka J • Spain – Arias-Loste M, Caballeria J, Crespo J, Romero-Gomez M & Lazarus J • United Kingdom – Anstee Q, & Day C • United States – Sanyal A, Loomba R & Younossi Z • CDA – Estes C

Methodology • Convened a panel of NAFLD experts in each country • Collect published epidemiology data for NAFLD • Gathered country specific rates for obesity and diabetes to estimate incidence • Used published work to estimate progression rates for non-alcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) • Modeled the disease progression • Validates the forecasts against reported NASH related HCC cases

Modeling Approach • Built a disease progression (Markov) model Obesity, Diabetes and NAFLD Relative Incidence • Populations were handled as stocks whereas 1.00 transition probabilities were handled as flows 0.80 • Started in 1950 to track steatosis onset for 0.60 most individuals 0.40 • The population was allowed to age through 1 0.20 year age cohorts by gender • Incidence rates of obesity and diabetes were 0.00 1980 1990 2000 2010 2020 2030 used to estimate new NAFLD cases Obesity incidence trend Diabetes incidence trend Relative Incidence of NAFLD

The Markov model took in into consideration th the reversible nature of f th the dis isease

NASH prevalence an and obesity in in th the EU5 ar are lo lower th than th the US % of total % of total % of NAFLD BMI≥30 population ≥15+ population ≥15+ with NASH with NAFLD with NASH US 28% 30% 20% 6.3% France 16% 25% 16% 4.2% Germany 19% 25% 18% 4.6% Italy 16% 28% 17% 4.9% Spain 18% 25% 17% 4.4% UK 21% 25% 18% 4.8%

Par arallel l Epidemics of f Dia iabetes an and Obesity in in th the US Centers for Disease Control and Prevention, National Center for Health Statistics. National Health Examination Survey and National Health and Nutrition Examination Survey. Health, United States 2006. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA, 311(8):806-814, 2014. National Center for Health Statistics. Health, United States, 2014. Hyattsville, MD. 2015. Available at: http://www.cdc.gov/nchs/data/hus/hus14.pdf

Obesity has been in increasing in in European countries as as well Adult Obesity Rate 30% 25% Adult obesity has been 20% increasing but the rate of 15% increase has slowed. 10% 5% 0% 1980 1990 2000 2010 2020 2030 UK Germany Spain France Italy

NASH populatio ion is is exp xpected to grow by 60% while cir cirrhotic cases will ill in increase by 160% in in US

NASH populatio ion is is exp xpected to grow by 45% while cir cirrhotic cases will ill in increase by 120% in in EU

The in increase in in NAFLD cases is is sl slowing down but NASH, , HCC, an and liv liver related deaths will ill in increase

Cost In Inputs • Annual direct costs per F4 / HCC patient were derived from the literature and inflated to 2016 USD based on Eurostat health inflation • Costs for compensated cirrhosis were applied to 10% of prevalent cases (2015) increasing to 50% (2030) reflecting increased awareness and diagnosis Annual Direct Cost per Patient (2016 USD) Annual Direct Cost per Patient (2016 USD) 60,000 250,000 50,000 200,000 40,000 Annual Cost Annual Cost 150,000 30,000 100,000 20,000 50,000 10,000 - - Compensated Cirrhosis Decompensated Cirrhosis Hepatocellular Carcinoma Liver Transplant Liver Transplant - Subseqent Years United States France Germany Italy Spain United Kingdom United States France Germany Italy Spain United Kingdom Eckman MH, Talal AH, Gordon SC, Schiff E, Sherman KE. Cost-effectiveness of screening for chronic hepatitis C infection in the United States. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2013;56(10):1382-93. Postma MJ, Wiessing L, Jager J. Updated healthcare estimates for drug-related hepatitis C infections in the European Union. In: Jager J, Limburg W, Kretzschmar M, Postma MJ, Wiessing L, editors. Hepatitis C and injecting drug use: impact, costs and policy options. EMCDDA Scientific Monograph Series, ISSN 1606-1691; No 7. 389 p. : ill. ; 24 cm. Luxembourg: Office for Official Publications of the European Communities; 2004. p. 203-16. Sullivan SD, Craxi A, Alberti A, et al. Cost effectiveness of peginterferon alpha-2a plus ribavirin versus interferon alpha-2b plus ribavirin as initial therapy for treatment-naive chronic hepatitis C. Pharmacoeconomics 2004; 22: 257-65. Eurostat. 2017. Database - HICP (2015 = 100) - annual data (average index and rate of change) for Health Category (CP06).

Estimated Dir irect US Healthcare Cost - NASH • Annual direct costs increase 260% from $4.9 B (2015) to $17.6 B (2030) • Decompensated cirrhosis comprises only ~1% of all prevalent NASH cases and ~10% of F4/HCC cases, but accounts for the majority of direct costs in this analysis • Assumed the number of liver transplants can not increase due to limited availability of donors Prevalent NASH Cases (F4 & HCC) – US, 2015-2030 NASH Costs – US, 2015-2030 4,000,000 20,000 Annual Cost (2016 USD Millions) 3,500,000 15,000 3,000,000 2,500,000 2,000,000 10,000 1,500,000 1,000,000 5,000 500,000 0 0 Compensated Cirrhosis Decompensated Cirrhosis Compensated Cirrhosis Decompensated Cirrhosis Hepatocellular Carcinoma Liver Transplant Hepatocellular Carcinoma Liver Transplant

Estimated Dir irect US Healthcare Cost - NASH • Decompensated cirrhosis comprises ~10% of F4/HCC cases but accounts for the majority of direct costs in all years 2015 US Costs 2015 US Prevalent Cases 0.4% 0.8% 5.9% 8.6% 10.3% 9.2% 88.6% 76.4% 2030 US Prevalent Cases 2030 US Costs 0.2% 0.7% 6.3% 2.3% 10.9% 31.5% 88.2% 59.9% Compensated Cirrhosis Decompensated Cirrhosis Hepatocellular Carcinoma Liver Transplant

Estimated Dir irect EU5 Hea ealthcare Cost - NASH • Annual direct costs increase 160% from $1.1 B (2015) to $3.9 B (2030) • Decompensated cirrhosis costs increases faster (160%) as compared to HCC (115%), while compensated cirrhosis costs increase ten-fold largely due to increased diagnosis • Assumed the number of liver transplants can not increase due to limited availability of donors Prevalent NASH Cases (F4 & HCC) – EU5, 2015-2030 NASH Costs – EU5, 2015-2030 2,500,000 4,500 Annual Cost (2016 USD Millions) 4,000 2,000,000 3,500 3,000 1,500,000 2,500 2,000 1,000,000 1,500 1,000 500,000 500 0 0 Compensated Cirrhosis Decompensated Cirrhosis Compensated Cirrhosis Decompensated Cirrhosis Hepatocellular Carcinoma Liver Transplant Hepatocellular Carcinoma Liver Transplant

Estimated Dir irect EU5 Hea ealthcare Cost - NASH • Similar to the US, most direct costs are incurred among decompensated cirrhosis cases in all years 2015 EU5 Costs 2015 EU5 Prevalent Cases 0.3% 0.9% 4.7% 7.4% 10.2% 10.5% 88.4% 77.7% 2030 EU5 Prevalent Cases 2030 US Costs 0.1% 0.8% 4.7% 1.5% 11.2% 35.1% 58.7% 87.9% Compensated Cirrhosis Decompensated Cirrhosis Hepatocellular Carcinoma Liver Transplant

Conclusions • In the absence of interventions, advanced liver diseases associated with NAFLD will more than double over the next 15 years • Direct healthcare costs in the US currently estimated at $4.9 billion increasing by 260% to $17.6 billion by 2030 without interventions • In the European Union, the current healthcare cost is estimate at $1.1 billion, which will increase by 160% to $3.9 billion by 2030 without interventions • Interventions are required to manage the increase in future disease burden and associated costs • Preventing progression to decompensated cirrhosis and HCC are critical for reducing direct healthcare costs • These same interventions will also have an impact on other non-communicable diseases including cardiovascular diseases and diabetes • Better reporting systems are required to track NAFLD related disease burden to measure progress