Hepatitis C Genotype 1 (GT 1) Patients in the United States (US) INDICATION is indicated with or without ribavirin for the treatment of patients with chronic hepatitis C virus (HCV) genotype 1, 4, 5, or 6 infection. 1
RECOMMENDED TREATMENT DURATION FOR HCV GT 1, 4, 5, OR 6 PATIENTS, INCLUDING THOSE WITH HCV/HIV-1 CO-INFECTION Please refer to the Drug Interactions section of the full Prescribing Information for dosage recommendations for concomitant HIV-1 antiviral drugs. 1 TABLET DAILY NO FOOD REQUIREMENT 8 + RBV Can be considered in treatment-naïve (TN) GT 1 patients without cirrhosis and with pre-treatment HCV RNA <6 million IU/mL 12 12 TN GT 1 patients without cirrhosis or with compensated cirrhosis (Child-Pugh A) Treatment-experienced (TE) a GT 1 patients without cirrhosis TN or TE a GT 4, GT 5 or GT 6 patients without cirrhosis or with compensated cirrhosis (Child-Pugh A) TN and TE a GT 1 patients with decompensated cirrhosis (Child-Pugh B or C) b TN and TE a GT 1 or GT 4 liver transplant recipients without cirrhosis or with compensated cirrhosis (Child-Pugh A) c 24 TE a GT 1 patients with compensated cirrhosis (Child- Pugh A) d a TE patients include those who have failed a peginterferon alfa + ribavirin (RBV)-based regimen with or without an HCV protease inhibitor. b In patients with decompensated cirrhosis (Child-Pugh B or C), the starting dosage of RBV is 600 mg and can be titrated up to 1000 mg for patients <75 kg and 1200 mg for those 75 kg in two divided doses with food. If the starting dosage of RBV is not well tolerated, the dosage should be reduced as clinically indicated based on hemoglobin levels. c The daily dosage of RBV is weight-based (1000 mg for patients <75 kg and 1200 mg for those 75 kg) administered orally in two divided doses with food. Refer to the RBV prescribing information. d + RBV for 12 weeks can be considered in TE GT 1 patients with compensated cirrhosis who are eligible for RBV. See footnote c for RBV dosage recommendations. ESTIMATED DISPOSITION OF CHRONIC HCV GT 1 PATIENTS IN THE US An estimated 3.5 million people in the US have chronic HCV. 2 Insight into the disposition of the HCV population receiving medical care in the US may help payers predict the size and scope of HCV management among their members. Contraindications If 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. Warnings and Precautions Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with 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.
The Ipsos Therapy Monitor study 3 is a standardized chart audit that records how physicians are managing their patients who have chronic HCV. These data provide a snapshot of the estimated percentages of GT 1, GT 4, GT 5, and GT 6 patients in the US who are receiving medical care 3 Overall, the genotype distribution in this study is consistent with the Centers for Disease Control and Prevention (CDC) estimates within the US population. 3,4 Among chronic HCV patients in this survey, approximately three-quarters were TN and less than one-quarter were TE (this may include experience with prior HCV protease inhibitors) 3 Ipsos Chart Audit January - December 2015 (N = 4910): estimated treatment experience distribution among HCV patients 3,a 3% 12% 19% 66% GT 1, TN GT 1, TE GT 4, 5, 6 a N = 4910 chronic HCV patients in the US (includes all patients with known genotype excluding those with sustained virologic response [SVR] or awaiting SVR results [weighted]). Other genotypes Ipsos Chart Audit January - December 2015 (N = 3021): estimated disposition by treatment experience and cirrhosis status among GT 1 patients 3,a a N = 3021 GT 1 chronic HCV patients in the US (includes all GT 1 patients with known fibrosis score [weighted]). Presence of cirrhosis was defined by a METAVIR fibrosis score of F4. 11% 17% 7% 65% GT 1, TN, noncirrhotic GT 1, TN, cirrhotic GT 1, TE, noncirrhotic GT 1, TE, cirrhotic 9% Ipsos Chart Audit January - December 2015 (N = 3021): disposition by METAVIR fibrosis score among GT 1 patients 3 24% 19% 28% 20% F0 (no liver damage) F1 (minimal liver damage) F2 (moderate liver damage) F3 (advanced liver damage) F4 (cirrhotic) Warnings and Precautions (continued) Risk of Reduced Therapeutic Effect of Due to P-gp Inducers: Rifampin and St. John s wort are not recommended for use with as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
A patient chart review based on online/mobile surveys with HCV-treating physicians tracked the intended duration of therapy for prescriptions within the US over time. This information can help provide a context for payers to estimate the number of patients that physicians may consider eligible for 8 weeks of therapy. Based on the most recent data available from 196 physicians representing 5368 patient charts, was initiated in 2063 TN, noncirrhotic (NC), GT 1 patients. Of those patients, 81% had a baseline viral load of <6 million (M) IU/mL. The following two figures show the intended lengths of therapy with for TN, NC, GT 1 patients with a viral load of <6M IU/mL first by average and then over time. 5 HCV Patient Initiation Tracker January 5, 2015 - January 3, 2016 (n = 1677): intended length of therapy (LOT) among TN, NC GT 1 patients with baseline viral load <6M IU/mL average 5 Initiations LOT (average) TN, NC GT 1 Patients with Baseline Viral Load <6M IU/mL (n = 1677) 8 weeks 68% 12 weeks 31% Other 1% Many TN, NC GT 1 patients with a viral load <6M IU/mL may be considered for an 8 week regimen. 1,3,5 HCV Patient Initiation Tracker January 5, 2015 - January 3, 2016 (n = 1677): LOT among TN, NC GT 1 patients with baseline viral load <6M IU/mL over time 5 3% 1% 1% 33% 34% 27% 31% % of Patient Charts 64% 66% 72% 68% 8 weeks 12 weeks Other Q1 2015 01/05/15 to 03/29/15 (n = 357) Q2 2015 03/30/15 to 06/21/15 (n = 405) Q3 2015 06/22/15 to 09/27/15 (n = 440) Q4 2015 09/28/15 to 01/03/16 (n = 475) Physicians were asked: What is the intended total length of therapy for the patient on? Warnings and Precautions (continued) Related Products Not Recommended: is not recommended for use with other products containing sofosbuvir. Adverse Reactions Most common ( 10%, all grades) adverse reactions were fatigue, headache and asthenia.
The fibrosis score distribution of GT 1 patients who could be considered to receive 8 weeks of (TN, NC with a baseline viral load <6M IU/mL) and received an intended 8 week LOT are shown in the chart below. HCV Patient Initiation Tracker January 5, 2015 - January 3, 2016 (n = 1130): intended LOT and fibrosis distribution among GT 1 patients who could be considered for an 8 week LOT (TN, NC with a baseline viral load <6M IU/mL) 5 % of Patient Charts 35% 35% 22% 8% F3 (advanced liver damage) F2 (moderate liver damage) F1 (minimal liver damage) F0 (no liver damage) 8 Week (n = 1130) AASLD/IDSA recommends early treatment for chronic HCV 6 [Clinicians] should treat HCV-infected patients with antiviral therapy with the goal of achieving an SVR, preferably early in the course of their chronic HCV infection before the development of severe liver disease and other complications. AASLD/IDSA Guidance 6 AASLD = American Association for the Study of Liver Diseases; IDSA = Infectious Diseases Society of America; SVR = sustained virologic response. Drug Interactions In addition to rifampin and St. John s wort, coadministration of 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. Coadministration of 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 for more information on potentially significant drug interactions, including clinical comments.
References: 1. full Prescribing Information, Foster City, CA: Gilead Sciences, Inc; February 2016. 2. Yehia BR, Schranz AJ, Umscheid CA, et al. The treatment cascade for chronic hepatitis C virus infection in the United States: a systematic review and meta-analysis. PLos ONE. 2014.9(7):e101554. 3. Ipsos HCV USA. Therapy Monitor. Q1 2015 - Q4 2015. 4. National Institutes of Health Consensus Development Conference statement: management of hepatitis C 2002 (June 10-12, 2002). Gastroenterology. 2002; 123: 2082-2099. 5. ZoomRx. HCV Initiation Chart Audit. HCV Initiation Tracker. January 5, 2015 to January 3, 2016. 6. AASLD/IDSA/IAS USA. When and in whom to initiate HCV therapy. Summary of recommendations for when and in whom to initiate HCV therapy. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org/full-report/when-and-whom-initiate-hcv-therapy. Updated February 24, 2016. Accessed February 26, 2016., the logo, GILEAD, and the GILEAD logo are trademarks of Gilead Sciences, Inc. or its related companies. 2016 Gilead Sciences, Inc. All rights reserved. HVNP0769 04/16