Patient Discussion Guide INFORMATION AND ANSWERS TO AID YOUR COUNSELING OF PATIENTS Please click to see full Prescribing Information for HARVONI, including BOXED WARNING.
CHRONIC HEPATITIS C (HEP C) GENOTYPE 1 (GT 1) PATIENT DISCUSSION GUIDE CHANGE IN HEP C CAN START WITH YOU CONTENTS: SCREEN DIAGNOSE CONNECT ABOUT HARVONI The goal for Hep C patients is to achieve cure. Cure, or sustained virologic response (SVR12), is defined as undetectable levels of HCV in the blood at 12 weeks after completion of therapy. 2,3 To help your patients with that goal, use this guide to: Counsel your patients about Hep C Answer questions that may arise Inform them about HARVONI as a treatment option for chronic HCV GT 1 patients YOUR ROLE You play a critical role in the management of your patients Hep C. Connection to treatment evaluation starts with you from screening patients to linking them to a treatment provider. INDICATION HARVONI is indicated for the treatment of adults with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis. HARVONI is used with ribavirin in GT 1 adults with decompensated cirrhosis and in GT 1 or 4 adult liver transplant recipients without cirrhosis or with compensated cirrhosis. IMPORTANT SAFETY INFORMATION BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HARVONI. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and posttreatment followup. Initiate appropriate patient management for HBV infection as clinically indicated. Contraindications If HARVONI is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information. Please click to see full Prescribing Information for HARVONI, including BOXED WARNING. 2
SCREENING FOR HEP C ANTIBODIES Of the approximately 3.5 million Americans with chronic Hep C infection, only half have been diagnosed. 4 KEY POINTS: In the United States, Hep C is the most common chronic blood-borne infection 5 50% of chronic Hep C patients in the United States are undiagnosed they don t know they have the infection 4 Approximately three-quarters of all those infected with Hep C are baby boomers (born 1945 1965) 6 The Centers for Disease Control and Prevention (CDC), US Preventive Services Task Force (USPSTF), and American Association for the Study of Liver Diseases (AASLD) recommend a one-time screening of all baby boomers for Hep C, regardless of other risk factors 3,6,7 For a comprehensive list of other reasons and risk factors for screening, visit the CDC website Screening for Hep C antibodies is accomplished through a simple blood test A positive Hep C antibody test result does not necessarily mean your patient has an active infection. Another blood test is needed to confirm the diagnosis of Hep C - If you choose a lab s reflex-testing option at the screening step, a second blood draw will not be necessary if your patient s antibody test is positive Hep C can be cured with treatments that are interferon-free 3
PATIENT QUESTION RECOMMENDED RESPONSE What is Hep C and why should I be screened for it? Hep C is a blood-borne virus that causes inflammation of the liver. It is important to identify if you have Hep C because the virus can damage your liver. Hep C can be cured, which means the virus is no longer detected when measured in the blood 3 months after treatment completion. Will my insurance cover the screening test? The Affordable Care Act requires all new private health plans to pay for screening of persons at high risk for infection and for the one-time screening of baby boomers, those born 1945 1965. 8,9 Medicare patients are covered without cost sharing. 9 Also, most state Medicaid programs cover preventive services for adults. 10 4
DIAGNOSING CHRONIC HEP C INFECTION About 20% 50% of patients clear the Hep C virus spontaneously within the first few months after initial infection. 3 Once people have been infected with HCV, they will always test positive for HCV antibodies. 11 KEY POINTS: If the antibody screening test is positive, a second blood test that detects and measures the amount of Hep C RNA (viral load) is needed to confirm a chronic infection Your patient will need to have another blood draw if the reflex-testing option was not selected when you ordered the screening test If the RNA test result is positive, your patient has an active Hep C infection, which means the virus is present in the blood Patients who do not have symptoms or who have a low viral load can still have liver disease progression 12 Remind the patient that Hep C can be cured 5
PATIENT QUESTION RECOMMENDED RESPONSE How did I get Hep C? How long have I had it? Hep C is a blood-borne virus that is spread by direct contact with the blood of an infected person. 13 It is possible to get Hep C by injecting drugs or using nonsterile tattoo needles. People who received blood transfusions before 1992 may also be at risk of having Hep C infection. While less likely, it s also possible to get it by sharing personal care items such as toothbrushes, razors, or nail clippers with someone who has Hep C. However, it cannot be spread through casual contact, including shaking hands or sharing food and drinks. There is more information about the ways it can be transmitted on the CDC hepatitis C webpage. We may never know exactly when you contracted Hep C. (Through sensitive patient-physician questioning and dialogue, a risk factor from your patient s history may be revealed.) What is Hep C doing to my body? Hep C is a serious disease that can result in long-term health problems, including liver damage, liver failure, or even death. 14 Why was my Hep C antibody test result positive, but my Hep C RNA test result was negative? A negative Hep C RNA test result means you were exposed to the virus, but you are not chronically infected with Hep C. Now that you ve confirmed I have Hep C, what happens next? The next step is to connect you with a Hep C treatment provider for evaluation. 6
CONNECTING PATIENTS TO TREATMENT EVALUATION Your staff s assistance in scheduling the first appointment can help ensure the patient follows through on the initial visit to the Hep C treatment provider. KEY POINTS: Tell your patient that you would like him/her to see a Hep C treatment provider Explain that the Hep C treatment provider will conduct more tests to evaluate the patient s liver health and determine treatment options Select a treatment provider who: Has experience currently treating patients with Hep C Is accepting new patients Can accommodate cultural or language preferences Has an office conveniently located for your patient The Hep C treatment provider will evaluate the patient and then discuss treatment options and next steps Assure the patient that you will be available to answer questions after the first treatment provider appointment and throughout any treatment At the end of the discussion with your patient, make sure: You have answered any questions he/she may have Your patient is motivated to connect with a Hep C treatment provider and move forward to possible treatment 7
PATIENT QUESTION RECOMMENDED RESPONSE What kind of tests will the treatment provider perform? Will you contact the treatment provider or help me contact the treatment provider to make an appointment? [If not already performed,] the treatment provider will confirm the diagnosis with a test that measures how much virus is in your blood (viral load). The treatment provider will also run tests to determine your genotype, assess the health of your liver, and test for hepatitis B. I can assist you in scheduling the treatment provider appointment and will contact you after the appointment as a follow-up. 8
HARVONI OVERVIEW HARVONI is a complete regimen taken as one pill, once daily for 12 weeks in the majority of patients with GT 1, 1 the most common GT in the United States. 15 KEY POINTS: HARVONI is an interferon- and ribavirin (RBV) free tablet taken once daily for 12 weeks in most patient types. 1 8 weeks can be considered in GT 1 treatment-naïve, non-cirrhotic patients with baseline viral load <6 million IU/mL 1 This dosing information does not include patients with decompensated cirrhosis (Child-Pugh B or C) or liver transplant recipients In the ION-1, ION-2, and ION-3 clinical trials, HARVONI delivered an overall cure rate (sustained virologic response, or SVR12) of 97% (n=1042/1079) in GT 1 patients 1 High cure rates (SVR12) were observed in a broad range of subjects, including those with compensated cirrhosis, previous treatment experience, advanced age, and high BMI 1,16-18 Across the ION-1, ION-2, and ION-3 clinical trials, adverse reactions (all grades) reported in 5% of subjects receiving 8, 12, or 24 weeks of treatment with HARVONI were fatigue (13% 18%), headache (11% 17%), nausea (6% 9%), diarrhea (3% 7%), and insomnia (3% 6%) 1 Discontinuation rates due to adverse events (AEs) were 0% 1% across HARVONI clinical trials 1 Study Designs: randomized, open-label trials in GT 1 subjects 1 ION-1 1,16 : TN subjects (N=865) without cirrhosis or with compensated cirrhosis were randomized to receive HARVONI for 12 weeks, HARVONI + RBV for 12 weeks, HARVONI for 24 weeks, or HARVONI + RBV for 24 weeks. ION-2 1,17 : TE subjects (N=440) without cirrhosis or with compensated cirrhosis were randomized to receive HARVONI for 12 weeks, HARVONI + RBV for 12 weeks, HARVONI for 24 weeks, or HARVONI + RBV for 24 weeks. ION-3 1,18 : TN subjects (N=647) without cirrhosis were randomized to receive HARVONI for 8 weeks, HARVONI + RBV for 8 weeks, or HARVONI for 12 weeks. These studies did not include patients with decompensated cirrhosis (Child-Pugh B or C) or liver transplant recipients. TN = treatment-naïve, TE = treatment-experienced patients who have failed treatment with either peginterferon (Peg-IFN) alfa + ribavirin (RBV) or an HCV protease inhibitor (PI) + Peg-IFN alfa + RBV, RBV = ribavirin IMPORTANT SAFETY INFORMATION Warnings and Precautions Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with HARVONI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia. Risk of Reduced Therapeutic Effect Due to P-gp Inducers: Rifampin and St. John s wort are not recommended for use with HARVONI as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations. Adverse Reactions Most common adverse reactions ( 10%, all grades) were fatigue, headache, and asthenia. Please click to see full Prescribing Information for HARVONI, including BOXED WARNING. 9
PATIENT QUESTION RECOMMENDED RESPONSE What is HARVONI? How long does treatment take? What results have patients who were treated with HARVONI achieved? HARVONI is a prescription medicine used to treat adults with chronic (lasting a long time) hepatitis C genotype (GT) 1, 4, 5 or 6 infection with or without cirrhosis (compensated). In those with GT 1 and advanced cirrhosis (decompensated) or with GT 1 or 4 with or without cirrhosis (compensated) who have had a liver transplant, HARVONI is used with ribavirin. 1 Your Hep C treatment provider will determine the length of your treatment, which may depend on whether or not you ve been treated before, the level of virus in your body, and how advanced your liver disease is. With HARVONI, there is no interferon or complicated regimens. 1 Across Phase 3 trials, HARVONI delivered an overall cure rate of 97% (n=1042/1079) in subjects with the most common type of Hep C. IMPORTANT SAFETY INFORMATION Drug Interactions In addition to rifampin and St. John s wort, coadministration of HARVONI is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of HARVONI. Coadministration of HARVONI is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively. Consult the full Prescribing Information for HARVONI for more information on potentially significant drug interactions, including clinical comments. Please click to see full Prescribing Information for HARVONI, including BOXED WARNING. 10
PATIENT QUESTION RECOMMENDED RESPONSE What will my Hep C treatment provider want to know about my health before starting HARVONI? IMPORTANT SAFETY INFORMATION Before taking HARVONI, tell your Hep C treatment provider all of your medical conditions, including if you: have ever had hepatitis B virus infection have liver problems other than hepatitis C infection have ever had a liver transplant have severe kidney problems or you are on dialysis have HIV infection are pregnant or plan to become pregnant. It is not known if HARVONI will harm your unborn baby. When taking HARVONI in combination with ribavirin, you should also read the ribavirin Medication Guide for important pregnancy information are breastfeeding or plan to breastfeed. It is not known if HARVONI passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take HARVONI BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HARVONI. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and posttreatment followup. Initiate appropriate patient management for HBV infection as clinically indicated. Please click to see full Prescribing Information for HARVONI, including BOXED WARNING. 11
PATIENT QUESTION RECOMMENDED RESPONSE What possible side effects can I expect? HARVONI may cause serious side effects, including: Hepatitis B (Hep B) reactivation: If you have a history of Hep B, and take HARVONI, your Hep B may become active again and cause serious liver problems including liver failure and death. Your healthcare provider will monitor you for Hep B infection during and after HARVONI treatment. Slow heart rate (bradycardia): HARVONI, when taken with amiodarone (Cordarone, Nexterone, Pacerone ), a medicine used to treat certain heart problems, may cause slow heart rate, which in some cases has led to death or the need for a pacemaker. Get medical help right away if you take amiodarone with HARVONI and get any of the following symptoms: fainting or near-fainting, dizziness or lightheadedness, not feeling well, weakness, extreme tiredness, shortness of breath, chest pains, confusion, or memory problems. The most common side effects of HARVONI include tiredness, headache, and weakness. 1 Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of HARVONI. For more information, ask your healthcare provider or pharmacist. IMPORTANT SAFETY INFORMATION Contraindications If HARVONI is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information. Please click to see full Prescribing Information for HARVONI, including BOXED WARNING. 12
PATIENT QUESTION RECOMMENDED RESPONSE What should I consider if I m taking other medications? Where can I get more information on HARVONI? Will my insurance cover HARVONI, and what part of the cost will I pay? Tell your Hep C treatment provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. HARVONI may affect the way certain other medicines work, and other medicines may affect how HARVONI works. 1 In addition to your doctor or Hep C treater, there are two great resources to get more information about HARVONI. You can call 844-READY41 to speak to a live educator or visit harvoni.com. Support Path can help you understand your insurance costs, verify your benefits, and assist with the prescription approval process. There is also a HARVONI co-pay coupon for eligible patients with commercial insurance. IMPORTANT SAFETY INFORMATION Warnings and Precautions Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with HARVONI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia. Risk of Reduced Therapeutic Effect Due to P-gp Inducers: Rifampin and St. John s wort are not recommended for use with HARVONI as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations. Adverse Reactions Most common adverse reactions ( 10%, all grades) were fatigue, headache, and asthenia. Please click to see full Prescribing Information for HARVONI, including BOXED WARNING. 13
IMPORTANT SAFETY INFORMATION Drug Interactions In addition to rifampin and St. John s wort, coadministration of HARVONI is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of HARVONI. Coadministration of HARVONI is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively. Consult the full Prescribing Information for HARVONI for more information on potentially significant drug interactions, including clinical comments. Please click to see full Prescribing Information for HARVONI, including BOXED WARNING. REFERENCES 1. HARVONI Prescribing Information. Gilead Sciences, Inc. Foster City, CA. April 2017. 2. US Department of Health and Human Services, Center for Drug Evaluation and Research. Draft Guidance for Industry. Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment. May 2016. 3. AASLD, IDSA, IAS-USA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Accessed September 21, 2017. 4. Yehia BR, Schranz AJ, Umscheid CA, Lo Re V. The treatment cascade for chronic hepatitis C virus infection in the United States: a systematic review and meta-analysis. PLoS One. 2014;9(7):1-7. 5. Centers for Disease Control and Prevention. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCVrelated chronic disease. MMWR Morb Mortal Wkly Rep. 1998;47(RR-19):1-39. 6. Smith BD, Morgan RL, Beckett GA, et al. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recomm Rep. 2012;61(RR-4):1-32. 7. US Preventive Services Task Force. Hepatitis C: Screening. https://www.uspreventiveservicestaskforce.org/page/document/recommendationstatementfinal/hepatitis-c-screening. Published June 25, 2013. Accessed August 23, 2017. 8. Moyer VA. Ann Intern Med. 2013;159:349-357. 9. CDC. https://www.cdc.gov/nchhstp/preventionthroughhealthcare/healthdepartments/ services.htm. Accessed July 19, 2017. 10. The AIDS Institute. Coverage Guide for Hepatitis C Testing. Revised June 2017. 11. Centers for Disease Control and Prevention. Hepatitis C: what to expect when getting tested. https://www.cdc.gov/hepatitis/hcv/pdfs/hepcgettingtested.pdf. Updated October 2013. Accessed August 23, 2017. 12. Heller T, Seeff LB. Viral load as a predictor of progression of chronic hepatitis C? Hepatology. 2005;42(6):1261-1263. 13. Centers for Disease Control and Prevention. HIV/AIDS and viral hepatitis. https://www.cdc.gov/hepatitis/populations/hiv.htm. Updated July 26, 2016. Accessed August 1, 2016. 14. Centers for Disease Control and Prevention. Hepatitis C FAQs for the public. https://www.cdc.gov/hepatitis/hcv/cfaq.htm. Updated October 17, 2016. Accessed August 23, 2017. 15. Messina JP, Humphreys I, Flaxman A, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology. 2015;61(1):77-87. 16. Afdhal N, Zeuzem S, Kwo P, et al; for the ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370(20):1889-1898. 17. Afdhal N, Reddy KR, Nelson DR, et al; for the ION-2 Investigators. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370(16):1483-1493. 18. Kowdley KV, Gordon SC, Reddy KR, et al; for the ION-3 Investigators. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014;370(20):1879-1888. HARVONI, the HARVONI logo, SUPPORT PATH, GILEAD, and the GILEAD logo are trademarks of Gilead Sciences, Inc., or its related companies. All other trademarks referenced herein are the property of their respective owners. 2017 Gilead Sciences, Inc. All rights reserved. HVNP1141 11/17 14