Update on Real-World Experience With HARVONI

Transcription

1 Update on Real-World Experience With A RESOURCE FOR PAYERS MAY 217 This information is intended for payers only. The HCV-TARGET study was supported by Gilead Sciences, Inc. Real-world experience data were derived from patient medical records. Such data are longitudinal and observational in nature, and are not based on controlled clinical studies. Results from these cohorts may differ from results seen in the membership of a particular payer. INDICATIONS AND USAGE 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. 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. Click here for full Prescribing Information including BOXED WARNING on hepatitis B reactivation.

2 1 TABLET ONCE A DAY Pill not actual size Ledipasvir (9 mg) An HCV NS5A inhibitor Sofosbuvir (4 mg) A nucleotide analog inhibitor of HCV NS5B polymerase 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. 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. 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. 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 post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated. 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. 1

3 RECOMMENDED TREATMENT DURATION FOR ADULTS WITH HCV GT 1, 4, 5, 6, INCLUDING THOSE WITH HCV/HIV-1 COINFECTION 1 1 TABLET DAILY 8 WEEKS Can be considered in treatment-naïve (TN) GT 1 patients without cirrhosis and with pre-treatment HCV RNA <6 million IU/mL 12 WEEKS 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) NO FOOD REQUIREMENT + RBV 12 WEEKS 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 WEEKS 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 6 mg and can be titrated up to 1 mg for patients <75 kg and 12 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 (1 mg for patients <75 kg and 12 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. Test all patients for evidence of current or prior HBV infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-hbc) before initiating HCV treatment with For patients with HCV/HIV-1 coinfection, follow the dosage recommendations above. Refer to the Drug Interactions section of the Prescribing Information for dosage recommendations for concomitant HIV-1 antiretroviral drugs No dosage recommendation can be given for patients with severe renal impairment (estimated Glomerular Filtration Rate [egfr] <3 ml/min/1.73 m 2 ) or with end-stage renal disease (ESRD) due to higher exposures (up to 2-fold) of the predominant sofosbuvir metabolite Clinical and hepatic laboratory monitoring, as clinically indicated, is recommended for patients with decompensated cirrhosis receiving treatment with and RBV Warnings and Precautions 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. 2

4 CLINICAL STUDIES IN ADULTS WITHOUT CIRRHOSIS OR WITH COMPENSATED CIRRHOSIS (CHILD-PUGH A) 1 Study Weeks ION-1 and ION-2 ION-3 ION-4 SIRIUS + RBV a + RBV a Primary endpoint: sustained virologic response (SVR12), defined as HCV RNA <25 IU/mL at 12 weeks after the cessation of treatment 1, b SVR12 is considered a virologic cure 2 + RBV a Baseline demographics ION-1 1 ION-2 1 ION-3 1 ION-4 1,3 SIRIUS 1 N Design Randomized, open-label Randomized, open-label Randomized, open-label Single-arm, open-label Randomized, placebo-controlled c Cirrhotics 16% (n = 136) 2% (n = 88) None 2% (n = 67) 1% (n = 155) Prior treatment TN Peg-IFNa + RBV or Peg-IFNa + RBV + HCV PI TN TN or RBV +/- PegIFN +/- HCV DAA Peg-IFNa + RBV followed by Peg-IFNa + RBV + HCV PI HCV GT GT 1 GT 1 GT 1 GT 1 or GT 4 d GT 1 HCV/HIV-1 coinfection No No No Yes No DAA = direct-acting antiviral agent; Peg-IFNa = peginterferon alfa. a RBV 1-12 mg/day. b Relapse was a secondary endpoint. c In the 12-week arm, subjects received placebo for 12 weeks followed by + RBV for 12 weeks. d GT 1, n = 327; GT 4, n = 8. Warnings and Precautions (cont.) Risk of Reduced Therapeutic Effect 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. 3

5 CLINICAL STUDIES IN ADULTS WITHOUT CIRRHOSIS OR WITH COMPENSATED CIRRHOSIS (CHILD-PUGH A) 1 (cont.) GT 1 patients achieving SVR12 with ± RBV Patients (%) % 96% 99% 96% 95% 96% 97% 1% 8 weeks 12 weeks + RBV 12 weeks 24 weeks 2 n = 123 n = 216 n = 213 n = 335 n = 87 n = 77 n = 77 n = 22 ION-3 a ION-3 ION-1 ION-4 b ION-2 SIRIUS SIRIUS ION-2 TN, NC TN, NC TN, NC/CC TN/TE, NC/CC TE, NC TE, CC TE, CC TE, CC CC = compensated cirrhosis (Child-Pugh A); NC = noncirrhotic. Adverse reactions (all grades) reported in 5% of GT 1 patients receiving for 8, 12, or 24 weeks: ION-1, ION-2, and ION-3 8 Weeks (N = 215) 12 Weeks (N = 539) 24 Weeks (N = 326) Fatigue 16% 13% 18% Headache 11% 14% 17% Nausea 6% 7% 9% Diarrhea 4% 3% 7% Insomnia 3% 5% 6% The safety profile in HCV/HIV-1 coinfected subjects (ION-4) was similar to that observed in HCV monoinfected subjects The most common adverse reactions occurring in at least 1% of subjects were headache (2%) and fatigue (17%) Direct comparisons across studies should not be made due to differing study designs Adverse reactions reported in 5% of TE, CC, GT 1 patients receiving for 24 weeks or + RBV for 12 weeks versus placebo: SIRIUS 24 Weeks (N = 78) + RBV 12 Weeks (N = 76) Placebo 12 Weeks (N = 77) Asthenia 31% 36% 23% Headache 29% 13% 16% Fatigue 18% 4% 1% Cough 5% 11% 1% Myalgia 9% 4% Dyspnea 3% 9% 1% Irritability 8% 7% 1% Dizziness 5% 1% Footnotes for all figures: a Subgroup of TN, NC, GT 1 HCV patients with baseline HCV RNA <6 million IU/mL. In ION-3, relapse rates for for 8 weeks were 2% (n = 2/123) in patients with baseline HCV RNA <6 million IU/mL and 1% (n = 9/92) in patients with baseline HCV RNA 6 million IU/mL. b Patients with GT 1 or 4 HCV with HIV coinfection. Adverse Reactions Most common adverse reactions ( 1%, all grades) were fatigue, headache, and asthenia. 4

6 REAL-WORLD EXPERIENCE: HCV-TARGET 4 Baseline demographics HCV-TARGET 8 Weeks a (N = 35) 12 Weeks (N = 971) 24 Weeks (N = 552) Male, n (%) 134 (44) 57 (59) 361 (65) Median age, years (range) 58 (18-84) 6 (21-87) 61 (23-83) Black, n (%) 68 (22) 39 (32) 16 (19) White, n (%) 219 (72) 591 (61) 46 (74) Prior HCV treatment, n (%) Experienced DAA-experienced HCV GT, n (%) 1a 1b 11 (4) 2 (1) 197 (65) 97 (32) 35 (36) 89 (9) 646 (67) 27 (28) 494 (9) 143 (26) 374 (68) 125 (23) Cirrhosis, n (%) 3 (1) 259 (27) 42 (76) Decompensated cirrhosis, n (%) b 5 (2) 14 (11) 189 (34) Median HCV RNA, log HIV, n (%) 1 (.3) 55 (6) 14 (3) The HCV-TARGET study evaluated the safety and efficacy of 8, 12, or 24 weeks of in real-world GT 1 adult patients in academic or community settings HCV-TARGET included GT 1 TN and TE patients without cirrhosis or with compensated cirrhosis (N = 299) SVR12 rates in HCV-TARGET excluded patients lost to follow-up The regimen was selected and administered at the clinician s discretion according to local standards of care DAA = direct-acting antiviral. a for 8 weeks can be considered in GT 1 TN, noncirrhotic patients with a baseline viral load <6 million IU/mL. b The recommended treatment regimen and duration for TN and TE GT 1 patients with decompensated cirrhosis (Child-Pugh B or C) is + ribavirin for 12 weeks. GT 1 adult patients achieving SVR12 with a Patients (%) Drug Interactions 96% 97% 95% 244/ /91 486/51 8 b 12 c 24 c Treatment Duration (Weeks) a Per-protocol population. b Subgroup of patients treated with 8 weeks according to label (ie, GT 1 TN, noncirrhotic, pretreatment HCV RNA <6 million IU/mL). c Of patients in HCV-TARGET who received alone for 12 or 24 weeks, 14 (11%) and 189 (34%) had decompensated cirrhosis, respectively. Treatment with for 8, 12, or 24 weeks resulted in overall SVR12 rates of 96% Of the total of 2356 patients that ended treatment with a -containing regimen: 2.8% (n = 67) of patients discontinued treatment (13 deaths, 12 were in patients with cirrhosis) 8% (n = 19) had insufficient follow-up or were lost to follow-up post-treatment Of the 299 patients in the per-protocol population (virological outcome known), 15% (n = 311) received + RBV for 12 weeks is recommended for TN GT 1 patients without cirrhosis or with compensated cirrhosis (Child-Pugh A) and for TE GT 1 patients without cirrhosis. for 8 weeks can be considered in TN GT 1 adults without cirrhosis who have pre-treatment HCV RNA <6 million IU/mL. for 24 weeks is recommended for TE GT 1 adults with compensated cirrhosis (Child-Pugh A). + RBV for 12 weeks can be considered in TE GT 1 patients with compensated cirrhosis (Child-Pugh A) who are eligible for RBV. 1 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. 5

7 REAL-WORLD EXPERIENCE: HCV-TARGET 4 (cont.) The overall SVR12 rate with treatment was 96% (n = 1788) GT 1 adult patients achieving SVR12 with a % 98% 94% 96% 97% Patients (%) / / / / /846 Overall Yes Cirrhosis No Naïve Experienced Prior Treatment a For 8 (n = 282), 12 (n = 91), or 24 (n = 51) weeks. Only patients who completed treatment with and have available virologic outcome included (per-protocol population). Adverse events reported in 5% of patients receiving in HCV-TARGET, n = 1927 (%) Any adverse event, n (%) 1217 (63) Nausea 155 (8.) Fatigue 436 (22.6) Diarrhea 123 (6.4) Headache 49 (21.2) Insomnia 117 (6.1) Infections and infestations 159 (8.3) 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 were fatigue (13%-18%), headache (11% 17%), nausea (6%-9%), diarrhea (3%-7%), and insomnia (3%-6%) 1 Patients who may be considered for 8 weeks of are adults with GT 1 HCV who are treatment-naïve without cirrhosis and have baseline HCV RNA <6 million IU/mL. In ION-3, relapse rates for for 8 weeks were 2% (n = 2/123) in patients with baseline HCV RNA <6 million IU/mL and 1% (n = 9/92) in patients with baseline HCV RNA 6 million IU/mL. 1 Drug Interactions (cont.) 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. 6

8 REAL-WORLD EXPERIENCE 4 Efficacy in adult patients who can be considered for 8 weeks of SVR12 rates in GT 1, TN, noncirrhotic patients with baseline HCV RNA <6 million IU/mL Patients (%) % 98% 8 weeks 12 weeks 2 244/ /296 HCV-TARGET in HCV GT 1 adults: Real-world experience from HCV-TARGET Patients achieving SVR12 with Patients (%) % 97% 8 weeks 12 weeks 2 n = 255 n = 91 HCV-TARGET HCV-TARGET <6 million IU/mL TN, NC TN, NC/CC Patients who may be considered for 8 weeks of are adults with GT 1 HCV who are treatment-naïve without cirrhosis and have baseline HCV RNA <6 million IU/mL. In ION-3, relapse rates for for 8 weeks were 2% (n = 2/123) in patients with baseline HCV RNA <6 million IU/mL and 1% (n = 9/92) in patients with baseline HCV RNA 6 million IU/mL. 1 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. 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 post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated. 7

9 REAL-WORLD EXPERIENCE: SUMMARY The HCV-TARGET study was supported by Gilead Sciences, Inc. Real-world experience data were derived from patient medical records. Such data are longitudinal and observational in nature, and are not based on controlled clinical studies. Results from these cohorts may differ from results seen in the membership of a particular payer. In HCV-TARGET, overall SVR12 rates of 96% were achieved in GT 1 adult patients regardless of duration of (8, 12, or 24 weeks) The overall discontinuation rate in HCV-TARGET was 2.8% The most common AEs were fatigue and headache Among GT 1 adult patients who may be considered for the 8-week regimen, SVR12 rates for those who actually received it were similar to SVR12 rates for those who received for 12 weeks instead Patients who may be considered for 8 weeks of are adults with GT 1 HCV who are treatmentnaïve without cirrhosis and have a baseline HCV RNA <6 million IU/mL. In ION-3, relapse rates for for 8 weeks were 2% (n = 2/123) in patients with baseline HCV RNA <6 million IU/mL and 1% (n = 9/92) in patients with baseline RNA 6 million IU/mL for 12 weeks is the recommended treatment duration for treatment-naïve patients without cirrhosis or with compensated cirrhosis. This does not include patients with decompensated cirrhosis (Child-Pugh B or C) or liver transplant recipients In ION-3, adverse reactions (all grades) reported in 5% of patients receiving 8 weeks of treatment with were fatigue, headache, and nausea 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 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. Risk of Reduced Therapeutic Effect 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. Adverse Reactions Most common adverse reactions ( 1%, all grades) were fatigue, headache, and asthenia. 8

10 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. Click here for full Prescribing Information including BOXED WARNING on hepatitis B reactivation. References. 1. [package insert]. Foster City, CA: Gilead Sciences, Inc.; April US Food and Drug Administration. Draft guidance for industry. Chronic hepatitis C virus infection: developing direct-acting antiviral drugs for treatment. May Naggie S, et al. N Engl J Med. 215;373: Terrault N, et al. Gastroenterology. 216;151: , the Logo, GILEAD, and the GILEAD Logo are trademarks of Gilead Sciences, Inc., or its related companies. 217 Gilead Sciences, Inc. All rights reserved. HVNP955 5/17