Senate Health Care Committee Briefing: Hepatitis C Treatment Dan Lessler, MD Chief Medical Officer November 20, 2014

Hepatitis C Overview Epidemiology & Risk Factors Clinical Course of Disease Treatments Treatment Costs and “ROI” HCA Policy Approach 2

Hepatitis C Caused by an RNA virus Prior to 1989, known as “Non-A, Non-B hepatitis” Multiple “types” – Type 1 most common – Types 2, 3 and 4 less common 3

Hepatitis C: Epidemiology Most common cause of chronic hepatitis C virus (HCV) Leading cause of cirrhosis and liver cancer in the U.S. Leading reason for liver transplantation in the U.S. Approximately 1% of U.S. general population has chronic hepatitis C infection Prevalence is greatest in those born between 1945 and 1965 – USPSTF recommends screening all people born between 1945 and

Hepatitis C: Risk Factors Blood to blood contact (e.g., IV drug use) Blood transfusion prior to 1992 Receive hemodialysis Received body piercing or tattoos with non-sterile instruments Known exposure to hepatitis C virus Infected with HIV Vertical transmission from infected mother to child in <10% of pregnancies Not spread by breastfeeding 5

Hepatitis C: Clinical Course Of every 100 people infected with hepatitis C: Between 15 and 25 will clear the infection will develop chronic infection; of these: – will go on to develop chronic liver disease (some degree of scarring) – 5-20 will go on to develop cirrhosis over a period of 2-30 years (more severe form of scarring) – 1-5 will die from cirrhosis and liver cancer 6

Hepatitis C: Clinical Manifestations Hepatitis C may lead to other complications, independent of stage of liver disease: – Kidney disease – Immunologic disorders – Profound fatigue 7

Hepatitis C: Treatment Goal: Sustained Viral Response (SVR) – No measurable virus – Proxy for “cure” Standard treatment, prior to 2011: peg- interferon and ribavirin (aka, “PR”) combination – High rate of toxicity – <50% effective in most common type of hepatitis C 8

“Breakthrough Treatments” First generation direct-acting antiviral (DAA) protease inhibitors approved for Type 1 Hepatitis C – Victrelis ® (boceprevir) wks + PR wks – Incivek ® (telaprevir) 12 wks + PR wks More effective than PR in achieving SVR (70%) Many pills taken about every 8 hours Marked increase in anemia (≤50%) Significant drug-drug interactions 9

2013 “Breakthrough Treatments” Sofosbuvir (Sovaldi ® ) and Simeprivir (Olysio™) Sofosbuvir (“Sovaldi”) – More effective than prior available treatments (up to 90% SVR) – Enables treatment without the use of interferon in genotypes 2 and 3 – For genotype 1 (most common type of HCV) and 4, still need interferon and ribavirin, but only for 12 weeks (vs weeks) – Cost ~$1000/pill 10

Hepatitis C: Breakthrough Treatments October 2014, FDA approves combination pill with sofosbuvir and ledipasvir (Harvoni ® ) – Highly effective and safe in the treatment of Hepatitis C genotype 1 (most common type) – One pill daily for 12 weeks (some may be treated in 8 weeks) – Interferon and ribivarin no longer necessary to treat type 1, thereby avoiding their toxicities 11

Hepatitis C: Breakthrough Treatments New pricing paradigm: – “Drug for a common disease, priced like an orphan drug.” (Steven Miller, MD; CMO Express Scripts) – Harvoni ~ $94,500 for typical course of treatment Additional “breakthrough” hepatitis C drugs from other manufacturers will soon be approved by FDA 12

Hepatitis C Treatment: Clinical Economics “Even at a 20 year horizon, if all patients infected with hep C are treated with the new regimens, the cost offset will only cover approximately ¾ of initial drug costs…” “…Costs saved by reducing liver-related complications in [a subgroup of patients with advanced fibrosis] would produce a net savings to the statewide [California] health care systems of approximately $1 billion after 20 years.” 13 Institute for Clinical and Economic Review, final report to the California Technology Assessment Forum, April 15, 2014

Hepatitis C: Prevalence Estimates Medicaid populations – Estimated prevalence: 21,000 PEB population – Estimated prevalence: 3,883 CDC estimates that ~50% of the U.S. population has been screened 14

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16 Whom to Treat Chronic HCV infection The need to prioritize – Limitations of workforce – Societal resources --- financial – Treat as many as resources allow How to prioritize – Those who will derive the most benefit --- highest risk of complications without treatment – Those that have the greatest impact on further transmission

17 Policy Development: Key Concepts Not all infected patients develop chronic liver disease Progression to more severe disease (cirrhosis) takes years Patients with more severe disease are at greatest risk of developing complications of cirrhosis and hepatocellular (liver) cancer

18 AASLD/IDSA: Highest Priority AASLD/IDSA: Highest Priority Patients with advanced fibrosis and compensated cirrhosis (Metavir F3/F4) Pre- & post-liver transplant recipients Severe extrahepatic (non-liver) complications of HCV -Type 2 or 3 essential mixed cryoglobulinemia with end-organ manifestations -HCV kidney disease: proteinuria, nephrotic syndrome or MPGN

HCA Hepatitis C Policy Development September 15, 2014 – Convened all payers/vendors (PEB and Medicaid) with whom HCA contracts – Discussed clinical approach to identifying and prioritizing the treatment of people with chronic hepatitis C infection – Goal: uniform clinical policy across all payers Policy drafted, sent for review and comment Current status: HCA finalizing clinical policy 19

Questions? Daniel Lessler, MD, MHA Chief Medical Officer