Sofosbuvir/Ledipasvir for HIV •
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Sofosbuvir for the Treatment of Genotype 1 Hepatitis C in Subjects Aged 65 Years Or Older
AMERICAN ASSOCIATION FOR THE STUDY OFLIVERD I S E ASES HEPATOLOGY, VOL. 63, NO. 4, 2016 Safety and Efficacy of Ledipasvir/ Sofosbuvir for the Treatment of Genotype 1 Hepatitis C in Subjects Aged 65 Years or Older Sammy Saab,1 Sarah H. Park,1 Masashi Mizokami,2 Masao Omata,3 Alessandra Mangia,4 Ed Eggleton,5 Yanni Zhu,5 Steven J. Knox,5 Phil Pang,5 Mani Subramanian,5 Kris Kowdley,6 and Nezam H. Afdhal7 Elderly subjects have been historically underrepresented in clinical trials involving antiviral hepatitis C therapies. The aim of this analysis was to retrospectively evaluate the safety and efficacy of ledipasvir/sofosbuvir (LDV/SOF) by age groups of <65 years versus 65 years among subjects enrolled in phase 3 trials. Four open-label phase 3 clinical trials evaluated the safety and efficacy of LDV/SOF with or without ribavirin (RBV) for the treatment of genotype 1 chronic hepatitis C virus. Sustained virological response at 12 weeks, treatment-emergent adverse events (AEs), and graded laboratory abnor- malities were analyzed according to age group. Of the 2293 subjects enrolled in four phase 3 trials, 264 (12%) were 65 years of age, of whom 24 were aged 75 years. Sustained virological response at 12 weeks was achieved by 97% (1965/ 2029) of subjects aged <65 years and 98% (258/264) of subjects aged 65 years. The most common AEs in both LDV/ SOF groups that occurred in 10% of subjects were headache and fatigue. The rate of study discontinuation due to AEs was similar in the two age cohorts. -
Ombitasvir, Paritaprevir/Ritonavir (Technivie )
Ombitasvir, paritaprevir/ritonavir (Technivie®) National Abbreviated Review Drug Monograph December 2015 VA Pharmacy Benefits Management Services, Medical Advisory Panel, VISN Pharmacist Executives and Office of Public Health The purpose of VA PBM Services drug monographs is to provide a comprehensive drug review for making formulary decisions. Updates will be made when new clinical data warrant additional formulary discussion. Documents will be placed in the Archive section when the information is deemed to be no longer current. FDA Approval Information1 Description/ Technivie is a fixed-dose combination of ombitasvir, paritaprevir, and ritonavir. Mechanism of Action Ritonavir does not have activity against Hepatitis C virus (HCV); it is included in the regimen as a pharmacokinetic enhancer (i.e. increase concentration of paritaprevir). The other two agents are direct-acting antivirals with different mechanisms of action. Ombitasvir is a NS5A inhibitor and paritaprevir is a NS3/4A protease inhibitor. Indication(s) under Review in Fixed-dose combination of ombitasvir, paritaprevir and ritonavir with ribavirin this document is indicated for the treatment of chronic hepatitis C genotype 4 infections in adults without cirrhosis. NOTE: Per prescribing information, this combination may be administered without ribavirin in treatment-naïve patients who cannot tolerate ribavirin Dosage Form(s) Under Ombitasvir, paritaprevir, ritonavir 12.5/75/50mg tablet Review REMS NO REMS Pregnancy Rating Pregnancy Category B; however, when ribavirin is co-administered, then regimen is contraindicated in pregnant women and in men whose female partners are pregnant. Executive Summary1-2 Efficacy The FDA approval of ombitasvir, paritaprevir and ritonavir with ribavirin was primarily based on one phase 2b randomized, open-label, multi-center trial (called PEARL-1). -
Hepatitis C Agents Therapeutic Class Review
Hepatitis C Agents Therapeutic Class Review (TCR) November 2, 2018 No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, digital scanning, or via any information storage or retrieval system without the express written consent of Magellan Rx Management. All requests for permission should be mailed to: Magellan Rx Management Attention: Legal Department 6950 Columbia Gateway Drive Columbia, Maryland 21046 The materials contained herein represent the opinions of the collective authors and editors and should not be construed to be the official representation of any professional organization or group, any state Pharmacy and Therapeutics committee, any state Medicaid Agency, or any other clinical committee. This material is not intended to be relied upon as medical advice for specific medical cases and nothing contained herein should be relied upon by any patient, medical professional or layperson seeking information about a specific course of treatment for a specific medical condition. All readers of this material are responsible for independently obtaining medical advice and guidance from their own physician and/or other medical professional in regard to the best course of treatment for their specific medical condition. This publication, inclusive of all forms contained herein, is intended to be educational in nature and is intended to be used for informational purposes only. Send comments and suggestions to [email protected]. Proprietary Information. Restricted Access – Do not disseminate or copy without approval. © 2004–2018 Magellan Rx Management. All Rights Reserved. FDA-APPROVED INDICATIONS Drug Mfr FDA-Approved Indications Interferons peginterferon alfa-2a Genentech Chronic hepatitis C (CHC) 1 (Pegasys®) . -
2015 Hepatitis C Second Generation Antivirals (Harvoni [Ledipasvir/Sofosbuvir], and Viekira Pak [Ombitasvir/Paritaprevir/Ritonavir
2015 Hepatitis C Second Generation Antivirals (Harvoni [ledipasvir/sofosbuvir], and Viekira Pak [ombitasvir/paritaprevir/ritonavir + dasabuvir ]) Prior Authorization – Through Preferred Agents Program Summary 2015 Hepatitis C Second Generation Antivirals (Harvoni [ledipasvir/sofosbuvir], and Viekira Pak [ombitasvir/paritaprevir/ritonavir + dasabuvir]) Prior Authorization – Through Preferred Oral Agent(s) The Hepatitis C First Generation, Hepatitis C Second Generation and Sovaldi Prior Authorization Programs must be implemented together. OBJECTIVE The intent of the Hepatitis C second generation antiviral Prior Authorization (PA) program is to appropriately select patients for therapy according to the Food and Drug Administration (FDA) approved product labeling and/or clinical guidelines and/or clinical studies. The PA process will evaluate the use of these agents when there is supporting clinical evidence of Class IIa, Level C or better for their use. Patients requesting Harvoni that are treatment naïve, non-cirrhotic and with an initial viral load < 6 M IU/mL will be approved for 8 weeks assuming all other criteria are met. This criteria does not include the use of Sovaldi (sofosbuvir), and requests for Sovaldi (sofosbuvir) in combination with Olysio (simeprevir) which will not be approved. For the use of Sovaldi (sofosbuvir) see Sovaldi specific criteria. For the use of Olysio in combination with peginterferon and ribavirin, see Hepatitis C First Generation criteria. For hepatocellular carcinoma patients, see Sovaldi (sofosbuvir) specific criteria. TARGET DRUGS Preferred Agent(s) Harvoni® (ledipasvir/sofosbuvir) Nonpreferred Agent(s) Viekira Pak (ombitasvir/paritaprevir/ritonavir + dasabuvir) PRIOR AUTHORIZATION CRITERIA FOR APPROVAL Harvoni (ledipasvir/sofosbuvir) will be approved when the following criteria are met: 1. The patient has a diagnosis of chronic hepatitis C confirmed by serological markers AND 2. -
Hepatitis C Treatment
Hepatitis C Treatment The goal of treatment for hepatitis C virus (HCV) is to cure the virus, which can be done with a combination of drugs. The specific meds used and the duration of treatment depend on a number of factors, including HCV genotype (genetic structure of the virus), viral load, past treatment experience, degree of liver damage, ability to tolerate the prescribed treatment, and whether the person is waiting for a liver transplant or is a transplant recipient. In some cases, HCV treatment may be limited by your health insurance plan or drug formulary. Here’s information about each type, or class, of approved HCV treatment along with drugs in the late stages of development: Multi-Class Combination Drugs Brand Name Generic Name Status Pharmaceutical Company Epclusa* sofosbuvir + velpatasvir Approved Gilead Sciences Harvoni* ledipasvir + sofosbuvir Approved Gilead Sciences Mavyret glecaprevir + pibrentasvir Approved AbbVie Vosevi sofosbuvir/velpatasvir/ Approved Gilead Sciences voxilaprevir Zepatier elbasvir + grazoprevir Approved Merck n/a daclatasvir + asunaprevir + Phase III Bristol-Myers Squibb beclabuvir *generic available What are they? Multi-class combination drugs are a combination of drugs formulated into a single pill or package of pills. For instance, the drug Harvoni combines two drugs, ledipasvir and sofosbuvir. Ledipasvir is an NS5A inhibitor and is only sold as part of Harvoni; sofosbuvir may be prescribed separately under the brand name of Sovaldi. Pegylated Interferon Alfa Brand Name Generic Name Status Pharmaceutical Company Pegasys peginterferon alfa-2a Approved Genentech What are they? Interferon is a protein made by the immune system, named because it interferes with viral reproduction. In addition, interferon signals the immune system to recognize and respond to microorganisms, including viral and bacterial infections. -
Study Protocol and Statistical Analysis Plan
Effects of Ledipasvir/Sofosbuvir on the Pharmacokinetics and Renal Safety of Tenofovir Alafenamide (TAF) NCT03126370 Protocol & Statistical Analysis Plan Version 03.29.2018 COMIRB Protocol COLORADO MULTIPLE INSTITUTIONAL REVIEW BOARD CAMPUS BOX F-490 TELEPHONE: 303-724-1055 Fax: 303-724-0990 Protocol #: 17-0490 Project Title: Effects of ledipasvir/sofosbuvir treatment on the pharmacokinetics and renal safety of tenofovir alafenamide (TAF) Principal Investigator: Jennifer J. Kiser, PharmD Version Number: 3.0 Version Date: 03/29/2018 I. Hypotheses and Specific Aims: Hypothesis: 1. Tenofovir plasma concentrations will be lower, tenofovir diphosphate concentrations in peripheral blood mononuclear cells will be higher, and tenofovir diphosphate concentrations in red blood cells (measured as dried blood spots, DBS) will be lower with tenofovir alafenamide relative to tenofovir disoproxil fumarate. 2. Tenofovir plasma and intracellular tenofovir diphosphate concentrations will increase when tenofovir alafenamide is co-administered with ledipasvir/sofosbuvir relative to TAF alone. 3. Markers of renal function (e.g. CrCl, urinary retinol binding protein/creatinine ratio and urinary beta-2 microglobulin/creatinine ratio) will not change when tenofovir alafenamide is coadministered with ledipasvir/sofosbuvir. Primary Aims: 1. Compare the area under the concentration time curve over the dosing interval (AUC0-24) of tenofovir in plasma when switched from tenofovir disoproxil fumarate (TDF) (Phase 1) to tenofovir alafenamide (TAF 25mg) (Phase 2), and compare the AUC0-24 of tenofovir in plasma given as TDF (Phase 1) to tenofovir in plasma in the form of TAF 25mg concomitantly with ledipasvir (LDV)/sofosbuvir (SOF) (Phase 3) 2. Compare TFV-DP in PBMCs between TDF (Phase 1) and TAF 25mg (Phase 2) and between TDF (Phase 1) and TAF 25mg plus LDV/SOF (Phase 3) Secondary Aims: 1. -
Update Sulle Terapie Farmacologiche Nell’Infezione Da Hcv
UPDATE SULLE TERAPIE FARMACOLOGICHE NELL’INFEZIONE DA HCV Giorgio Barbarini Già responsabile Unità Semplice “Diagnosi e terapia delle Malattie Infettive correlate alla Tossicodipendenza” DIPARTIMENTO MALATTIE INFETTIVE E TROPICALI April 21, 1989 Hepatitis C is the silent global epidemic of the 21st Century 2015 • ~72 million people with viraemic HCV • ~8.1 million people with HCV-related liver cirrhosis • ~261,000 people with HCV-related HCC • ~7000 HCV-related liver transplants • ~370,000 HCV liver-related deaths Viraemic prevalence 0.0–<0.6% 0.6–<0.8% 0.8–<1.3% 1.3–<2.9% 2.9–<6.7% Blach S, et al. Lancet Gastroenterol Hepatol 2017;2:161–76; The Polaris Observatory. Hepatitis C. Available at: http://polarisobservatory.org/polaris/hepC.htm (accessed April 2017) Seroprevalence of Hepatitis C: 150 to 200 Million Worldwide Eastern Europe 10 M Western Pacific 60 M United States Western Europe 5M 5 M Southeast Asia Highest Prevalence: 30-35 M Egypt-4M Americas (45% adults >40y) 12-15 M Africa 30-40M Australia .2 M 1. World Health Organization. Wkly Epidemiol Rec. 2000;75:17-28. 2. Edlin B et al. AASLD; November 11-15; 2005 San Francisco, California. Oral Presentation #44. 3. Fontanet A. Annual Report of Emerging Diseases for Year 2005. Accessed 03/13/06 at http://www.pasteur.fr/recherche/RAR/RAR2005/Epimal-en.html Distribution of HCV in the EU Viremic prevalence 0.64% Total viremic pool 3,238,000 New yearly infections 57,900 (plus ~30,000 from immigration) Lancet Gastroenterol Hepatol 2017;2:325-336 The European Union HCV Collaborators: Lancet Gastroenterol Hepatol 2017; 2: 325-36. -
Report on the Deliberation Results September 14, 2016 Evaluation and Licensing Division, Pharmaceutical Safety and Environmental
Report on the Deliberation Results September 14, 2016 Evaluation and Licensing Division, Pharmaceutical Safety and Environmental Health Bureau Ministry of Health, Labour and Welfare Brand Name Rebetol Capsules 200 mg Non-proprietary Name Ribavirin (JAN*) Applicant MSD K.K. Date of Application December 25, 2015 Results of Deliberation In the meeting held on September 9, 2016, the Second Committee on New Drugs concluded that the partial change application for the product may be approved and that this result should be presented to the Pharmaceutical Affairs Department of the Pharmaceutical Affairs and Food Sanitation Council. The re-examination period of the product is the time to the expiration date of the re-examination period for Viekirax Combination Tablets specified at the initial approval (until September 27, 2023). Conditions of Approval The applicant is required to develop and appropriately implement a risk management plan. *Japanese Accepted Name (modified INN) This English translation of this Japanese review report is intended to serve as reference material made available for the convenience of users. In the event of any inconsistency between the Japanese original and this English translation, the Japanese original shall take precedence. PMDA will not be responsible for any consequence resulting from the use of this reference English translation. Review Report August 23, 2016 Pharmaceuticals and Medical Devices Agency The following are the results of the review of the following pharmaceutical products submitted for marketing approvals conducted by the Pharmaceuticals and Medical Devices Agency. Brand Names (a) Viekirax Combination Tablets (b) Rebetol Capsules 200 mg Non-proprietary Names (a) Ombitasvir Hydrate/Paritaprevir Hydrate/Ritonavir (b) Ribavirin Applicants (a) AbbVie GK (b) MSD K.K. -
Ledipasvir/Sofosbuvir
Drug and Biologic Coverage Policy Effective Date ............................................ 9/1/2021 Next Review Date… ..................................... 9/1/2022 Coverage Policy Number ............................... IP0186 Ledipasvir/Sofosbuvir Table of Contents Related Coverage Resources Overview .............................................................. 1 Authorized Generics Medical Necessity Criteria ................................... 1 Interferon Therapy Reauthorization Criteria ....................................... 4 Omnibus Codes Authorization Duration ......................................... 4 Conditions Not Covered....................................... 5 Background .......................................................... 6 References .......................................................... 8 INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the -
Evaluation and Management of Chronic Hepatitis C Virus Infection
EVALUATION AND MANAGEMENT OF CHRONIC HEPATITIS C VIRUS (HCV) INFECTION Federal Bureau of Prisons Clinical Guidance MAY 2017 Federal Bureau of Prisons (BOP) Clinical Guidance is made available to the public for informational purposes only. The BOP does not warrant this guidance for any other purpose, and assumes no responsibility for any injury or damage resulting from the reliance thereof. Proper medical practice necessitates that all cases are evaluated on an individual basis and that treatment decisions are patient- specific. Consult the BOP Health Management Resources Web page to determine the date of the most recent update to this document: http://www.bop.gov/resources/health_care_mngmt.jsp. Federal Bureau of Prisons Evaluation and Management of Chronic HCV Infection Clinical Guidance May 2017 WHAT’S NEW IN BOP GUIDANCE REGARDING HCV INFECTION? The major changes included in this May 2017 update to the BOP guidance on chronic HCV infection are based primarily on the April 2017 changes to the American Association for the Study of Liver Diseases (AASLD) guidelines, as follows: • The term resistance-associated substitutions (RASs) is now being used instead of resistance- associated variants (RAVs). • Anti-HBs and anti-HBc, in addition to HBsAg, are recommended for baseline testing of hepatitis B status (see LABORATORY TESTS under BASELINE EVALUATION). • Ledipasvir/sofosbuvir once daily for eight weeks is now an AASLD-recommended regimen for treatment in a subgroup of HCV-infected persons who have genotype 1a or 1b, have an HCV viral load <6 million IU/ml, and are treatment-naïve—but who are not black, are not HIV-coinfected, and do not have cirrhosis. -
Web Annex 3.1. Adult Hepatitis C Virus Treatment Systematic Review
Web Annex 3.1. Adult hepatitis C virus treatment systematic review Michael Zoratti, Hamilton, Canada In: Guidelines for the care and treatment of persons diagnosed with chronic hepatitis C virus infection July 2018 i WHO/CDS/HIV/18.36 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial- ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. Zoratti M. Web Annex 3.1. Adult hepatitis C virus treatment systematic review. In: Guidelines for the care and treatment of persons diagnosed with chronic hepatitis C virus infection. -
TECHNIVIE (Ombitasvir, Paritaprevir and Ritonavir) Tablets, for Oral Use WARNINGS and PRECAUTIONS Initial U.S
HIGHLIGHTS OF PRESCRIBING INFORMATION • Co-administration with drugs that are: highly dependent on CYP3A for These highlights do not include all the information needed to use clearance; moderate and strong inducers of CYP3A. (4) TECHNIVIE safely and effectively. See full prescribing information for • Known hypersensitivity to ritonavir (e.g. toxic epidermal necrolysis, TECHNIVIE. Stevens-Johnson syndrome). (4) TECHNIVIE (ombitasvir, paritaprevir and ritonavir) tablets, for oral use WARNINGS AND PRECAUTIONS Initial U.S. Approval: 2015 • Risk of Hepatitis B Virus Reactivation: Test all patients for evidence of current or prior HBV infection before WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN initiation of HCV treatment. Monitor HCV/HBV coinfected patients for PATIENTS COINFECTED WITH HCV AND HBV HBV reactivation and hepatitis flare during HCV treatment and post- See full prescribing information for complete boxed warning. treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated. (5.1) Hepatitis B virus (HBV) reactivation has been reported, in some cases • Hepatic Decompensation and Hepatic Failure in Patient with Cirrhosis: resulting in fulminant hepatitis, hepatic failure, and death. (5.1) Hepatic decompensation and hepatic failure, including liver transplantation or fatal outcomes, have been reported mostly in patients with cirrhosis. RECENT MAJOR CHANGES Monitor for clinical signs and symptoms of hepatic decompensation, and Boxed Warning 2/2017 discontinue treatment in patients who develop evidence of hepatic Indication and Usage (1) 2/2017 decompensation. (5.2) Dosage and Administration (2.1) 2/2017 • ALT Elevations: Discontinue ethinyl estradiol-containing medications prior to starting TECHNIVIE (alternative contraceptive methods are Dosage and Administration (2.2) 2/2017 recommended).