Harvoni: solution to HCV PRESENTATION BY: PATRICK HO, USC PHARM D. CANDIDATE OF 2017 MENTOR: DR. CRAIG STERN, PHARMD, MBA, RPH, FASCP, FASHP, FICA, FLMI, FAMCP
Hepatitis C (HCV) Inflammation of the liver, characterized by hepatocyte necrosis An enveloped, single stranded, positive sense RNA virus The most common chronic bloodborne infection in the United States Prevalence: 1.6% (2.0*) 3.2 (5.2*) million persons live with HCV infection Genotype 1 (72%) Genotype 2 (16% to 19%) Genotype 3 (8% to 19%) Gritsenko D, Hughes G. Ledipasvir/Sofosbuvir (harvoni): improving options for hepatitis C virus infection. P T. 2015;40(4):256-76. http://www.hepatitis.va.gov/provider/reviews/genotypes.asp
Progression of Hepatitis C http://www.hepfi.org/hepatitis/hepatitis-c.html http://www.hepatitisc.uw.edu/go/evaluation-staging-monitoring/natural-history/core-concept/all
Goals of Pharmacological Treatment Sustained virological response (SVR) Continued absence of detectable HCV RNA at least 12 weeks after completion of therapy SVR is a marker for cure of HCV infection and has been shown to be durable in large prospective studies in more than 99% of patients followed up for > 5 years 1 Prevent complications from HCV infection Necroinflammation Fibrosis Cirrhosis Hepatocellular carcinoma Death 1 Swain MG, et al. Gastroenterology. 2010;139(5):1593 601.
History of HCV Treatment (genotype 1) Pegylated interferon + oral ribavirin SVR 45-50% 2 Relapse 13% to 18% 1 1 st gen protease inhibitors + pegylated interferon alfa-2a + ribavirin SVR 67-75% 2 2 nd gen protease inhibitors e.g. simeprevir SVR 79.2% 3 RNA polymerase nonstructural protein (NS5B) inhibitor sofosbuvir SVR 90% 4 1 http://www.scielo.br/scielo.php?script=sci_arttext&pid=s1413-86702007000600006 2 Gritsenko D, Hughes G. Ledipasvir/Sofosbuvir (harvoni): improving options for hepatitis C virus infection. P T. 2015;40(4):256-76. 3 Forns X, Lawitz E, Zeuzem S, et al. Simeprevir with peginterferon and ribavirin leads to high rates of SVR in patients with HCV genotype 1 who relapsed after previous therapy: a phase 3 trial. Gastroenterology. 2014;146(7):1669-79.e3. 4 Sofosbuvir [package insert]. Foster City, CA: Gilead Sciences; 2015.
What is Harvoni? Fixed-dose combination in a single pill taken once daily: Sofosbuvir 400 mg NS5B Polymerase Inhibitor Ledipasvir 90 mg NS5A inhibitor Indicated for HCV genotypes 1, 4, 5, 6 SVR 96% - 8 clinical trials that demonstrate >90% efficacy One tablet taken orally once daily with or without food Recommended treatment duration for GT 1: Treatment naïve with or without cirrhosis: 12 weeks Treatment experienced without cirrhosis: 12 weeks Treatment experienced with cirrhosis: 24 weeks Recommended treatment duration for other GTs: 12 weeks Harvoni [package insert]. Gilead Sciences, Inc. Foster City, CA. https://www.gilead.com/~/media/files/pdfs/medicines/liver-disease/harvoni/harvoni_pi.pdf. Published February 2016. Accessed May 19, 2016.
Who is Harvoni being recommended by? Department of Veterans Affairs (VA) National Hepatitis C Resource Center Program and National Viral Hepatitis Program American Liver Foundation European Association for the Study of the Liver (EASL) 2016 AASLD/ISDA Guideline - American Association for the Study of Liver Diseases and Infectious Diseases Society of America Harvoni (ledipasvir 90 mg/sofosbuvir 400 mg) Rating: Class I, Level A Daily sofosbuvir (400 mg) and weight-based RBV for 24 weeks Rating Class IIb, Level A http://hepc.liverfoundation.org/treatment/the-basics-about-hepatitis-c-treatment/medication-regimens-according-to-genotype/ Chronic Hepatitis C Virus (HCV) Infection: Treatment Considerations from the Department of Veterans Affairs National Hepatitis C Resource Center Program and the National Viral Hepatitis Program in the Office of Patient Care Services. http://www.hepatitis.va.gov/pdf/treatment-considerations-2016-03-28.pdf. Accessed May 19,2016. AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Accessed May 19, 2016.
Harvoni is cost-effective! Interferon and ribavirin overall combined cost: $25,000 for 48 weeks SVR 50%, Relapse 18% Cost / (SVR - Relapse) = $781.25 Harvoni Cost: $94,500 for 12 week course SVR 96%, Relapse 1% Cost / (SVR Relapse) = $994.74 Cost and Medication Access: The wholesale acquisition cost (WAC) for ledipasvirsofosbuvir is $1125 per pill. 1 Cost of 8-week course of therapy = $63,000 Cost of 12-week course of therapy = $94,500 Annals of Internal Medicine cost effectiveness study - Harvoni vs. older standard of care requiring a protease inhibitor, interferon and ribavirin 83% cost effective for treatment-naïve and 81% for treatment-experienced http://www.fpnotebook.com/mobile/gi/lvr/hptscantvrlrgmn.htm http://www.hepatitisc.uw.edu/page/treatment/drugs/ribavirin-drug#cost_and_medication_access http://www.hepmag.com/article/harvoni-cost-effectiveness-26971-61558283 http://www.hepatitisc.uw.edu/page/treatment/drugs/ledipasvir-sofosbuvir
Why Harvoni? One course cure to HCV Once daily oral tablet formulation promotes patient adherence Sustained virological response 96% with low relapse 1% Pregnancy category B No need for IFN (flu-like syndrome) or ribavirin (preg cat X) Well tolerated Fatigue, headache, nausea, diarrhea 1 Cost-effective Harvoni [package insert]. Gilead Sciences, Inc. Foster City, CA. https://www.gilead.com/~/media/files/pdfs/medicines/liver-disease/harvoni/harvoni_pi.pdf. Published February 2016. Accessed May 19, 2016.
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