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 years1

Prevent complications from HCV infection

Necroinflammation

Fibrosis

Cirrhosis

Hepatocellular carcinoma

Death

1Swain 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

1st gen protease inhibitors + pegylated interferon alfa-2a + ribavirin

SVR 67-75%2

2nd gen protease inhibitors e.g. simeprevir

SVR 79.2%3

RNA polymerase nonstructural protein (NS5B) inhibitor sofosbuvir

SVR 90%4

1http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702007000600006 2Gritsenko D, Hughes G. Ledipasvir/Sofosbuvir (harvoni): improving options for hepatitis C virus infection. P T. 2015;40(4):256-76. 3Forns 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.

4Sofosbuvir [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 ledipasvir-

sofosbuvir 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, diarrhea1

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.

The end