Population Viral Kinetic Modeling: SVR Prediction in HCV GT-3 Cirrhotic Patients With 24 Weeks of Daclatasvir + Sofosbuvir Administration

Size: px
Start display at page:

Download "Population Viral Kinetic Modeling: SVR Prediction in HCV GT-3 Cirrhotic Patients With 24 Weeks of Daclatasvir + Sofosbuvir Administration"

Transcription

1 Population Viral Kinetic Modeling: SVR Prediction in HCV GT-3 Cirrhotic Patients With 24 Weeks of Daclatasvir + Sofosbuvir Administration Emi Tafoya, Yasong Lu, Melody Luo, Premkumar Narasimhan, Neelima Thanneer, Brenda Cirincione, Timothy Eley, Nannan Zhou, Dennis Hernandez, Fiona McPhee, Tarek Leil Bristol-Myers Squibb, Princeton, NJ, USA; Bristol-Myers Squibb, Wallingford, CT, USA 16th International Workshop on Clinical Pharmacology of HIV & Hepatitis Therapy. Washington DC, USA, May 2015 Oral Presentation #3

2 Disclosures All authors are a full time employee and may also be stockholders of Bristol-Myers Squibb 2

3 An Unmet Medical Need: Effective and Safe Treatment for HCV GT 3 24 weeks of SOF + RBV approved in US Suboptimal in some populations/ anemia issues with RBV DCV+SOF now preferred regimen in EU for GT-3 Treatment experience Drug Duration (weeks) SVR12 (%) No cirrhosis SVR12 (%) With cirrhosis Naive IFNintolerant, ineligible, unwilling Previously IFN treated SOF+RBV Previously IFN treated Naive Previously IFN treated Study FISSION POSITRON FUSION VALENCE Sovaldi (sofosbuvir) US label 2013; SOF, sofosbuvir; RBV, ribavirin; HCV, hepatitis C virus (HCV); GT, genotype (GT) 3

4 An Unmet Medical Need: Effective and Safe Treatment for HCV GT 3 cont. Even lower SVR for GT-3 reported in real-world studies Study Boson EASL 2015 Abstract L05 (Foster G et al) Patient Population SOF+RBV 16 weeks %SVR12 SOF+RBV 24 weeks %SVR12 Cirrhosis Cirrhosis Treatment Naïve Treatment experienced HCV-TARGET Abstract P0840 EASL 2015 (Alqahtani S et al) Cirrhosis Cirrhosis Treatment Naïve - 78 Treatment experienced

5 ALLY-3 Study (AI444218) Phase 3 patients with chronic HCV GT 3 infection Treatment experienced subjects includes patients who previously failed treatment with interferon-based therapies or other anti-hcv therapies, including sofosbuvir Treatment-naive (N = 101) Treatment-experienced (N = 51) DCV 60 mg + SOF 400 mg QD DCV 60 mg + SOF 400 mg QD Follow-up Day 1 Week 12 Week 24 Week 36 SVR12 a DCV, daclatasvir; (DCV); CHC, chronic hepatitis C; SVR12, sustained virologic response rate at 12 weeks posttreatment; naive; treatment naive 5

6 ALLY-3 Study Patients Parameter HCV RNA level, n (%) Treatment-Naive Treatment-Experienced N=101 N=51 < 800,000 IU/mL 31 (31) 13 (25) 800,000 IU/mL 70 (69) 38 (75) IL28B genotype, n (%) CC 40 (40) 20 (39) CT 47 (47) 21 (41) TT 14 (14) 10 (20) Cirrhosis, n (%) d,e 19 (19) 13 (25) Fibrosis stage by FibroTest, n (%) f F0-F3 76 (75) 43 (84) F4 22 (22) 8 (16) d Cirrhosis was determined by liver biopsy (METAVIR F4; n=14), FibroScan (>14.6 kpa; n=11), or FibroTest score 0.75 and APRI >2 (n=7); for 11 patients, cirrhosis status was missing or inconclusive (FibroTest score >0.48 to <0.75 or APRI >1 to 2). e Of the 32 patients with cirrhosis, 11 (34%) had baseline platelet counts of cells/l. f Per the study protocol, FibroTest assessments were performed during screening (FibroTest scores not available for 3 treatment-naive patients); F0-F3 defined as FibroTest score of 0.74 and F4 defined as FibroTest score of >

7 ALLY-3 Study Result and Question Drug Duration Cirrhosis Observed SVR12 (%) DCV + SOF 12 wks 24 wks YES 63% NO 96% YES? NO? Reduced SVR12 rate in cirrhotic subjects HCV GT-3 cirrhotic patients may benefit from longer treatment duration without RBV However, longer duration was not studied 7

8 Population Viral Kinetic (PVK) M&S Goal Supporting 24 weeks of DCV + SOF without added RBV by SVR simulation Drug Duration Cirrhosis DCV + SOF 12 wks 24 wks Observed SVR12 (%) Simulated SVR12 (%) Simulated SVR24 (%) YES 63% Z Y NO 96% Z Y YES Not tested Y Y NO Not tested Y Y Y for prediction and Z for validation SVR12 data base lock was used 8

9 PVK Modeling Characteristics PVK model was characterized by a competition between a drug-susceptible strain and a drug-resistant strain in a HCV two-strain model Drug-resistant strain for each patient was identified by Population-based sequencing data of HCV RNA Resistance profiles established by using cell-based HCV replicon assays 9

10 PVK Modeling Characteristics cont. Base Model Covariates Replication capacity of drug-resistant strain Cirrhosis status Statistical Methodology MCMC Bayesian Laplacian algorithm (NONMEM 7.2) Diagnostic tests: conditional prediction of VK, VPC and convergence test SVR simulation 12 wks/24 wks of therapy, cirrhosis+ / cirrhosis For each scenario, 500 trials were simulated 100 hypothetical subjects were included in each trial 10

11 HCV Kinetics in Patients With DCV + SOF Reality: More HCV variants The two-strain model: a plausible and feasible simplification Other negligible mutants The most significant variant resistant to DCV Wildtype Mutation The most significant doubleresistant variant The most significant variant resistant to SOF 11

12 HCV Kinetics in Patients With DCV + SOF Drug-susceptible strains (Treatment effective) Other negligible mutants The most significant variant resistant to DCV Drug-resistant strains (Treatment ineffective) Wildtype Mutation The most significant doubleresistant variant The most significant variant resistant to SOF What will be the most significant variant? 12

13 Method to Identify the Most Significant Resistant Variant Replication capacity EC 50 Ranked resistance data (DCV) Rank Mutation 1 L31M 2 A30K 3 Y93H 4 S62N 5 M28V 6 S62I 7 S62T 8 A30S Linear stability analysis of the non-infectious steady state in the two-strain model was used for ranking HCV genome Total # of amino acids (Population Sequencing) NS5B ~591 NS5A Clinical Prevalence Population-based sequencing data (baseline) Subject N5A-M28 N5A-A30 N5A-L31 N5A-S62 N5A-Y T H 3 T 4 V Result Subject Resistant strains 1 None 2 Y93H 3 S62T 4 None 13

14 Variables in the BMS HCV Two-strain Model 14

15 Infection and Spontaneous Clearance of HCV RNA 15

16 Virion Clearance and Cell Death Virion clearance and cell death 16

17 Liver Cell Proliferation 17

18 Virion Production and Mutation Before Treatment p s cr 1 c : Replication capacity r f 1 18

19 Virion Production and Mutation With Treatment 19

20 Pre-specified Cirrhosis Covariates Based on Biology/Clinical Knowledge Inflammation in the liver possibly alters the parameters Theoretical difference in PK profile in cirrhotics within liver (systemic minimal Δ) 20

21 VK and SVR12 Achievement Adequately Described in 150/150 Subjects O: Observed VK Green: Estimated VK Blue: End of Treatment Red: Follow-up after treatment (4 wks and 12 wks) 21

22 Improved SVR for Patients With Cirrhosis Was Predicted by 24 Weeks of DCV + SOF Median SVR rate (5% - 95% CI) across 500 trials 100 hypothetical subjects were included in each trial Drug Duration Cirrhosis DCV + SOF 12 wks 24 wks Observed SVR12 (%) Simulated SVR12 (%) Simulated SVR24 (%) YES (50-70) 57 (47-68) NO (90-96) 93 (89-95) YES Not tested 89 (78-97) 89 (78-97) NO Not tested 99 (97-100) 99 (97-100) 22

23 Summary Mechanistic PVK M&S effectively characterized the 12 week DCV + SOF treatment efficacy data in GT 3 cirrhotic and non-cirrhotic patients Mechanistic PVK M&S predicted the efficacy of 24 weeks of therapy in GT 3 cirrhotic and non-cirrhotic patients This PVK approach supports 24 weeks of DCV + SOF without ribavirin for HCV GT 3 cirrhotic patients, a population with high unmet medical need 23

Case 4: A 61-year-old man with HCV genotype 3 with cirrhosis. Ira M. Jacobson, M.D. Weill Cornell Medical College New York, New York USA

Case 4: A 61-year-old man with HCV genotype 3 with cirrhosis. Ira M. Jacobson, M.D. Weill Cornell Medical College New York, New York USA Case 4: A 61-year-old man with HCV genotype 3 with cirrhosis Ira M. Jacobson, M.D. Weill Cornell Medical College New York, New York USA 1 Genotype 3 case 61-year-old man with HCV genotype 3 Cirrhosis on

More information

5/12/2016. Learning Objectives. Management of Hepatitis C Virus Genotype 2 or 3 Infected Treatment-Naive or Experienced Patients

5/12/2016. Learning Objectives. Management of Hepatitis C Virus Genotype 2 or 3 Infected Treatment-Naive or Experienced Patients 5/12/216 Management of Hepatitis C Virus Genotype 2 or 3 Infected Treatment-Naive or Experienced Patients Alexander Monto, MD Professor of Clinical Medicine University of California San Francisco San Francisco,

More information

Treatment of HCV infection in daily clinical practice. Which are the optimal options for Genotypes 2 and 3? Jiannis Vlachogiannakos

Treatment of HCV infection in daily clinical practice. Which are the optimal options for Genotypes 2 and 3? Jiannis Vlachogiannakos Treatment of HCV infection in daily clinical practice. Which are the optimal options for Genotypes 2 and 3? Jiannis Vlachogiannakos Associate Professor of Gastroenterology Academic Department of Gastroenterology

More information

Phase 3. Treatment Experienced. Ledipasvir-Sofosbuvir +/- Ribavirin in HCV Genotype 1 ION-2. Afdhal N, et al. N Engl J Med. 2014;370:

Phase 3. Treatment Experienced. Ledipasvir-Sofosbuvir +/- Ribavirin in HCV Genotype 1 ION-2. Afdhal N, et al. N Engl J Med. 2014;370: Phase 3 Treatment Experienced Ledipasvir-Sofosbuvir +/- Ribavirin in HCV Genotype 1 ION-2 Afdhal N, et al. N Engl J Med. 2014;370:1483-93. Ledipasvir-Sofosbuvir +/- Ribavirin in Treatment-Experienced HCV

More information

Daklinza Sovaldi. Daklinza (daclatasvir) and Sovaldi (sofosbuvir) Description

Daklinza Sovaldi. Daklinza (daclatasvir) and Sovaldi (sofosbuvir) Description Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 Subject: Daklinza Sovaldi Page: 1 of 4 Last Review Date: September 18, 2015 Daklinza Sovaldi Description

More information

HCV In 2015: Maximizing SVR

HCV In 2015: Maximizing SVR HCV In 2015: Maximizing SVR Alnoor Ramji Gastroenterology & Hepatology Clinical Associate Professor Division of Gastroenterology University Of British Columbia ramji_a@hotmail.com Disclosures (within Last

More information

Daklinza Sovaldi. Daklinza (daclatasvir) and Sovaldi (sofosbuvir) Description

Daklinza Sovaldi. Daklinza (daclatasvir) and Sovaldi (sofosbuvir) Description Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.01.36 Subject: Daklinza Page: 1 of 8 Last Review Date: March 18, 2016 Daklinza Description Daklinza (daclatasvir)

More information

Daklinza Sovaldi. Daklinza (daclatasvir) and Sovaldi (sofosbuvir) Description

Daklinza Sovaldi. Daklinza (daclatasvir) and Sovaldi (sofosbuvir) Description Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 Subject: Daklinza Sovaldi Page: 1 of 7 Last Review Date: June 24, 2016 Daklinza Sovaldi Description Daklinza

More information

C-CREST study, Part A: GZR + EBR or MK MK-3682 for genotypes 1, 2 and 3 - Phase II

C-CREST study, Part A: GZR + EBR or MK MK-3682 for genotypes 1, 2 and 3 - Phase II Design 18 years Chronic HCV infection Genotype 1, 2 or 3 Treatment-naïve HCV RNA 1 IU/ml No cirrhosis * No HBV or HIV co-infection Randomisation Open-label * Liver biopsy or Fibroscan 12.5 kpa or Fibrotest

More information

Dr. Siddharth Srivastava

Dr. Siddharth Srivastava Dr. Siddharth Srivastava MD, DM (Gastroenterology) Associate Professor GIPMER, New Delhi Rashtriya Gaurav Award 2013 for work on hepatitis B and C Set up Liver clinic at GIPMER and in charge EUS laboratory.

More information

How to optimize treatment in G3 patients? Jérôme GOURNAY, MD Hépatologie Centre Hospitalier Universitaire de Nantes France

How to optimize treatment in G3 patients? Jérôme GOURNAY, MD Hépatologie Centre Hospitalier Universitaire de Nantes France How to optimize treatment in G3 patients? Jérôme GOURNAY, MD Hépatologie Centre Hospitalier Universitaire de Nantes France Paris Hepatitis Conference, January 12, 2016 Disclosures I have received funding

More information

Technology appraisal guidance Published: 25 November 2015 nice.org.uk/guidance/ta364

Technology appraisal guidance Published: 25 November 2015 nice.org.uk/guidance/ta364 Daclatasvir for treating chronic hepatitis C Technology appraisal guidance Published: 25 November 2015 nice.org.uk/guidance/ta364 NICE 2018. All rights reserved. Subject to Notice of rights (https://www.nice.org.uk/terms-and-conditions#notice-ofrights).

More information

Rome, February nd Riunione Annuale AISF th AISF ANNUAL MEETING

Rome, February nd Riunione Annuale AISF th AISF ANNUAL MEETING Rome, February 20-21 nd 2014 Riunione Annuale AISF 2014 14 th AISF ANNUAL MEETING Present and future treatment strategies for patients with HCV infection: chronic hepatitis and special populations IFN

More information

Clinical Сase A previously relapse to PEG IFN + RBV in HCV G3a patient. Konstantin Zhdanov

Clinical Сase A previously relapse to PEG IFN + RBV in HCV G3a patient. Konstantin Zhdanov Clinical Сase A previously relapse to PEG IFN + RBV in HCV G3a patient Konstantin Zhdanov Genotype 3 in Europe Canada Norway Germany Sweden Czech Republic Poland Approximately 1/3 of HCV-infected patients

More information

TREATMENT OF GENOTYPE 2

TREATMENT OF GENOTYPE 2 Treatment of Genotype 2, 3,and 4 David E. Bernstein, MD, FACG Advisory Committee/Board Member: AbbVie Pharmaceuticals, Gilead, Merck, Janssen Consultant: AbbVie Pharmaceuticals, Bristol-Myers Squibb, Gilead,

More information

Treatments of Genotype 2, 3,and 4: Now and in the future

Treatments of Genotype 2, 3,and 4: Now and in the future Treatments of Genotype 2, 3,and 4: Now and in the future THERAPY FOR THE TREATMENT OF GENOTYPE 2 1 GT 2 and GT 3 Treatment-Naïve: SOF+RBV vs PEG-IFN+RBV FISSION Study Design HCV GT 2 and GT 3 Treatment-naïve

More information

Harvoni. Harvoni (ledipasvir & sofosbuvir) Description

Harvoni. Harvoni (ledipasvir & sofosbuvir) Description Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 Subject: Harvoni Page: 1 of 7 Last Review Date: June 19, 2015 Harvoni Description Harvoni (ledipasvir &

More information

Latest Treatment Updates for GT 2 and GT 3 Patients

Latest Treatment Updates for GT 2 and GT 3 Patients Latest Treatment Updates for GT 2 and GT 3 Patients Eric Lawitz, MD, AGAF, CPI Vice President, Scientific and Research Development The Texas Liver Institute Clinical Professor of Medicine University of

More information

Harvoni. Harvoni (ledipasvir & sofosbuvir) Description

Harvoni. Harvoni (ledipasvir & sofosbuvir) Description Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.03.32 Subject: Harvoni Page: 1 of 7 Last Review Date: December 3, 2015 Harvoni Description Harvoni (ledipasvir

More information

10/4/2016. Management of Hepatitis C Virus Genotype 2 or 3 Infection

10/4/2016. Management of Hepatitis C Virus Genotype 2 or 3 Infection Management of Hepatitis C Virus Genotype 2 or 3 Infection Kenneth E. Sherman, MD, PHD Gould Professor of Medicine Director, Division of Digestive Diseases University of Cincinnati Cincinnati, Ohio FORMATTED:

More information

SURVEYOR-II Part 2 Study Design

SURVEYOR-II Part 2 Study Design HIGH SVR RATES WITH + CO-ADMINISTERED FOR 8 WEEKS IN NON-CIRRHOTIC PATIENTS WITH HCV GENOTYPE 3 INFECTION A.J. Muir, S. Strasser, S. Wang, S. Shafran, M. Bonacini, P. Kwo, D. Wyles, E. Gane, S.S. Lovell,

More information

Harvoni. Harvoni (ledipasvir & sofosbuvir) Description

Harvoni. Harvoni (ledipasvir & sofosbuvir) Description Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.01.32 Subject: Harvoni Page: 1 of 9 Last Review Date: March 18, 2016 Harvoni Description Harvoni (ledipasvir

More information

Update on chronic hepatitis C treatment: current trends, new challenges, what next?

Update on chronic hepatitis C treatment: current trends, new challenges, what next? Update on chronic hepatitis C treatment: current trends, new challenges, what next? Matti Maimets 12.06.2015 MMaimets15 Disclosure this presentation is sponsored by Gilead Sciences MMaimets15 MMaimets15

More information

Current Treatment Options for HCV Patients. Michael Manns Dept. of Gastroenterology, Hepatology and Endocrinology Hannover Germany

Current Treatment Options for HCV Patients. Michael Manns Dept. of Gastroenterology, Hepatology and Endocrinology Hannover Germany Current Treatment Options for HCV Patients Michael Manns Dept. of Gastroenterology, Hepatology and Endocrinology Hannover Germany 7th International Congress of Internal Medicine of Central Greece, Larissa,

More information

Tough Cases in HIV/HCV Coinfection

Tough Cases in HIV/HCV Coinfection NORTHWEST AIDS EDUCATION AND TRAINING CENTER Tough Cases in HIV/HCV Coinfection John Scott, MD, MSc Assistant Professor University of Washington Presentation prepared by: J Scott Last Updated: Jun 5, 2014

More information

Expert Perspectives: Best of HCV from EASL 2015

Expert Perspectives: Best of HCV from EASL 2015 Best of HCV from EASL 2015 Expert Perspectives: Best of HCV from EASL 2015 Saeed Hamid, MD Alex Thompson, MD, PhD This activity is supported by educational grants from AbbVie, Bristol-Myers Squibb, and

More information

What do we need to know about RAVs clinically?

What do we need to know about RAVs clinically? 14 th European HIV & Hepatitis Workshop Rome, 25-27 May, 2016 What do we need to know about RAVs clinically? Stefan Zeuzem, MD University of Frankfurt Germany Background Resistance associated variants

More information

PEARL-I. Ombitasvir + Paritaprevir + Ritonavir +/- Ribavirin in HCV GT4. Treatment Naïve and Treatment Experienced

PEARL-I. Ombitasvir + Paritaprevir + Ritonavir +/- Ribavirin in HCV GT4. Treatment Naïve and Treatment Experienced Phase 2b Treatment Naïve and Treatment Experienced Ombitasvir + Paritaprevir + Ritonavir +/- Ribavirin in HCV GT4 PEARL-I Hézode C, et al. Lancet. 2015 March 30. [Epub ahead of print] PEARL-I: Study Design

More information

The Liver Meeting 2013: The 64th Annual Meeting of the AASLD Washington, DC, November 1 5, 2013 Presentation LB-1

The Liver Meeting 2013: The 64th Annual Meeting of the AASLD Washington, DC, November 1 5, 2013 Presentation LB-1 Phase 2b Study of the Interferon-Free and Ribavirin-Free Combination of Daclatasvir, Asunaprevir, and BMS-791325 for 12 Weeks in Treatment-Naive Patients With Chronic HCV Genotype 1 Infection Everson GT,

More information

Program Disclosure. Provider is approved by the California Board of Registered Nursing, Provider #13664, for 1.5 contact hours.

Program Disclosure. Provider is approved by the California Board of Registered Nursing, Provider #13664, for 1.5 contact hours. Program Disclosure This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint-sponsorship

More information

Hepatitis C Direct-Acting Antivirals

Hepatitis C Direct-Acting Antivirals Hepatitis C Direct-Acting Antivirals Goals: Approve use of cost-effective treatments supported by the medical evidence. Provide consistent patient evaluations across all hepatitis C treatments. Ensure

More information

SYNOPSIS Final Clinical Study Report for Study AI444031

SYNOPSIS Final Clinical Study Report for Study AI444031 Name of Sponsor/Company: Bristol-Myers Squibb Name of Finished Product: Name of Active Ingredient: () Individual Study Table Referring to the Dossier (For National Authority Use Only) SYNOPSIS for Study

More information

Harvoni. Harvoni (ledipasvir & sofosbuvir) Description

Harvoni. Harvoni (ledipasvir & sofosbuvir) Description Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.01.32 Subject: Harvoni Page: 1 of 9 Last Review Date: December 2, 2016 Harvoni Description Harvoni (ledipasvir

More information

EASL 2013 Interferon Free, All Oral Regimens for Hepatitis C. Maria Buti Hospital Universitario Valle Hebron Barcelona Spain

EASL 2013 Interferon Free, All Oral Regimens for Hepatitis C. Maria Buti Hospital Universitario Valle Hebron Barcelona Spain EASL 2013 Interferon Free, All Oral Regimens for Hepatitis C Maria Buti Hospital Universitario Valle Hebron Barcelona Spain The first Results with Oral therapy: a Protease Inhibitor and NS5A inhibitor

More information

Prior Authorization Guideline

Prior Authorization Guideline Prior Authorization Guideline Guideline Name Olysio (simeprevir) Formulary UnitedHealthcare Community & State Formulary Note Approval Date 2/19/2014 Revision Date 7/9/2014 1. Indications Drug Name: Olysio

More information

Virological tools for hepatitis C: re-treatment and resistance. Joop Arends Will Irving. by author

Virological tools for hepatitis C: re-treatment and resistance. Joop Arends Will Irving. by author Virological tools for hepatitis C: re-treatment and resistance Joop Arends Will Irving Disclosures Joop Arends Advisory board: Gilead, Abbvie, Janssen, MSD, BMS (research) grants: Abbvie, BMS, MSD and

More information

Treating HCV Genotype 2 & 3

Treating HCV Genotype 2 & 3 Treating HCV Genotype 2 & 3 3rd Workshop on HCV Therapy Advances, Rome 14.12.2013 Christoph Sarrazin Klinikum der J. W. Goethe-Universität Frankfurt am Main, Germany HCV Genotypes 2 & 3 Laurel and Hardy

More information

SVR Updates from the 2013 EASL

SVR Updates from the 2013 EASL Updates from the 2013 EASL By Tracy Swan, Treatment Action Group Streamlining HCV Treatment Treatment for hepatitis C virus (HCV) is becoming simpler, shorter, and more effective. All-oral combinations

More information

Saeed Hamid, MD Alex Thompson, MD, PhD

Saeed Hamid, MD Alex Thompson, MD, PhD Saeed Hamid, MD Alex Thompson, MD, PhD 1 We will review some top line data from EASL Majority of the time discussing how the data affects daily practice 2 Grazoprevir (GZR; MK-5172) + Elbasvir (EBR; MK-

More information

Hepatitis C Resistance Associated Variants (RAVs)

Hepatitis C Resistance Associated Variants (RAVs) Hepatitis C Resistance Associated Variants (RAVs) Atif Zaman, MD MPH Oregon Health & Science University Professor of Medicine Division of Gastroenterology and Hepatology Nothing to disclose Disclosure

More information

Hepatitis C Treatment 2014

Hepatitis C Treatment 2014 Hepatitis C Treatment 214 Brendan M. McGuire, MD UAB Liver Center Outline Epidemiology/National History Terminology for Treatment Treatment Considerations Current Treatment Options Genotype 1 (GT 1) Genotype

More information

Ledipasvir-Sofosbuvir (Harvoni)

Ledipasvir-Sofosbuvir (Harvoni) HEPATITIS WEB STUDY HEPATITIS C ONLINE Ledipasvir-Sofosbuvir (Harvoni) Robert G. Gish MD Professor, Consultant, Stanford University Medical Center Senior Medical Director, St Josephs Hospital and Medical

More information

Approved regimens for cirrhotic patients

Approved regimens for cirrhotic patients 5th Workshop on HCV THERAPY ADVANCES New antivirals in clinical practice Approved regimens for cirrhotic patients Amsterdam, 4-5 december 2015 Disease burden in Spain 400000 350000 300000 F0 Peak cirrhosis

More information

Emerging Therapies for HCV: Highlights from AASLD 2012 (Part 1)

Emerging Therapies for HCV: Highlights from AASLD 2012 (Part 1) Emerging Therapies for HCV: Highlights from AASLD 2012 (Part 1) Goals for Hepatitis C Therapy Compared to PegIFN/RBV, new products should offer: Improved efficacy Efficacy in all patient types including

More information

HCV Drug Resistance: Regulatory Perspective

HCV Drug Resistance: Regulatory Perspective HCV Drug Resistance: Regulatory Perspective Patrick Harrington, PhD Senior Clinical Virology Reviewer Division of Antiviral Products, FDA/CDER 2016 HIV and Hepatitis Clinical Pharmacology Workshop Washington,

More information

Hepatitis C Medications Prior Authorization Criteria

Hepatitis C Medications Prior Authorization Criteria Hepatitis C Medications Authorization Criteria Epclusa (/velpatasvir), Harvoni (ledipasvir/), Sovaldi (), Daklinza (daclatasvir), Zepatier (elbasvir/grazoprevir), Olysio (simeprevir), Viekira Pak (ombitasvir/paritaprevir/ritonavir;

More information

SOLAR-1 (Cohorts A and B)

SOLAR-1 (Cohorts A and B) Phase 2 Treatment Naïve and Treatment Experienced Ledipasvir-Sofosbuvir + RBV in HCV GT 1,4 and Advanced Liver Disease SOLAR-1 (Cohorts A and B) Charlton M, al. Gastroenterology. 2015; 149:649-59. Ledipasvir-Sofosbuvir

More information

Hepatitis C Introduction and Overview

Hepatitis C Introduction and Overview Hepatitis C Introduction and Overview Michael S. Saag, MD Professor of Medicine Associate Dean of Global Health Director, Center for AIDS Research University of Alabama at Birmingham Birmingham, Alabama

More information

Failure after treatment with DAAs: What to do? Marseille France 2-3 th June 2016

Failure after treatment with DAAs: What to do? Marseille France 2-3 th June 2016 Failure after treatment with DAAs: What to do? Marc Bourliere, MD White Nights of Hepatology Hôpital Saint Joseph Saint Petersburg Marseille France 2-3 th June 16 Disclosures Board member for : Schering-Plough,

More information

Treatment of Hepatitis C in HIV-Coinfected Patients. Vincent Soriano Department of Infectious Diseases Hospital Carlos III Madrid, Spain

Treatment of Hepatitis C in HIV-Coinfected Patients. Vincent Soriano Department of Infectious Diseases Hospital Carlos III Madrid, Spain Treatment of Hepatitis C in HIV-Coinfected Patients Vincent Soriano Department of Infectious Diseases Hospital Carlos III Madrid, Spain Estimated no. of persons infected with HIV and hepatitis viruses

More information

Management of HCV Tawesak Tanwandee

Management of HCV Tawesak Tanwandee Management of HCV 2016 Tawesak Tanwandee Topics Burden of HCV in our countries Natural history and unmet need for HCV treatment Current treatment as for 2016 Conclusion Evolution from HCV infection to

More information

Is HCV drug resistance an issue?

Is HCV drug resistance an issue? Is HCV drug resistance an issue? 5TH ASIAN CONFERENCE ON HEPATITIS&AIDS NANJING, CHINA 28-29 MAY 2016 FROM BASIC SCIENCE TO CLINICAL PRACTIC Jürgen Kurt Rockstroh Department of Medicine I, University Hospital

More information

Treatement Experienced patients without cirrhosis. Rafael Esteban Hospital Universitario Valle Hebron Barcelona

Treatement Experienced patients without cirrhosis. Rafael Esteban Hospital Universitario Valle Hebron Barcelona Treatement Experienced patients without cirrhosis Rafael Esteban Hospital Universitario Valle Hebron Barcelona Agenda With IFN PegIFN+ Ribavirin + Simeprevir PegIFN+ Ribavirin+ Sofosbuvir Without IFN Sofosbuvir

More information

What is the Optimized Treatment Duration? To Overtreat versus Undertreat. Nancy Reau, MD Associate Professor of Medicine University of Chicago

What is the Optimized Treatment Duration? To Overtreat versus Undertreat. Nancy Reau, MD Associate Professor of Medicine University of Chicago What is the Optimized Treatment Duration? To Overtreat versus Undertreat Nancy Reau, MD Associate Professor of Medicine University of Chicago Learning Objectives: 1. Discuss patient populations appropriate

More information

Clinical Criteria for Hepatitis C (HCV) Therapy

Clinical Criteria for Hepatitis C (HCV) Therapy Clinical Criteria for Hepatitis C (HCV) Therapy Pre-Treatment Evaluation o Must have chronic hepatitis C and HCV genotype and sub-genotype documented; o Patients who have prior exposure to DAA therapy

More information

HCV Infection: EASL Clinical Practice Guidelines Francesco Negro University Hospital Geneva Switzerland

HCV Infection: EASL Clinical Practice Guidelines Francesco Negro University Hospital Geneva Switzerland HCV Infection: EASL Clinical Practice Guidelines 2016 Francesco Negro University Hospital Geneva Switzerland Panel Codinat: Jean-Michel Pawlotsky Panel: Alessio Aghemo David Back Geoffrey Dusheiko Xavier

More information

HCV Treatment Failure: What Next? Dr Ashley Brown, Imperial College Healthcare NHS Trust, London

HCV Treatment Failure: What Next? Dr Ashley Brown, Imperial College Healthcare NHS Trust, London HCV Treatment Failure: What Next? Dr Ashley Brown, Imperial College Healthcare NHS Trust, London European HIV Hepatitis Co-infection Conference QEII Conference Centre 10 th December 2015 Dr Ashley Brown

More information

Simeprevir + PEG + RBV in Treatment-Naïve Genotype 1 QUEST-1 Trial

Simeprevir + PEG + RBV in Treatment-Naïve Genotype 1 QUEST-1 Trial Phase 3 Treatment Naïve Simeprevir + in Treatment-Naïve Genotype 1 QUEST-1 Trial Jacobson IM, et al. Lancet. 2014;384:403-13. Simeprevir + PEG + Ribavirin for Treatment-Naïve HCV GT1 QUEST-1 Trial QUEST-1

More information

Protocol. This trial protocol has been provided by the authors to give readers additional information about their work.

Protocol. This trial protocol has been provided by the authors to give readers additional information about their work. Protocol This trial protocol has been provided by the authors to give readers additional information about their work. Protocol for: Wyles DL, Ruane PJ, Sulkowski MS, et al. Daclatasvir plus sofosbuvir

More information

HCV Resistance Associated variants: impact on chronic hepatitis C treatment

HCV Resistance Associated variants: impact on chronic hepatitis C treatment HCV Resistance Associated variants: impact on chronic hepatitis C treatment Dr. Stéphane Chevaliez Associate Professor of Medicine at the University of Paris-Est. History of Resistance in HCV Concern Only

More information

Treating now vs. post transplant

Treating now vs. post transplant Resistance with treatment failure Treating now vs. post transplant Pros (for treating pre transplant) If SVR efficacy means Better quality of life Removal from waiting list No post transplant recurrence

More information

Glecaprevir-Pibrentasvir in Non-Cirrhotic Genotype 2 ENDURANCE-2

Glecaprevir-Pibrentasvir in Non-Cirrhotic Genotype 2 ENDURANCE-2 Phase 3 Treatment Naïve or Experienced Glecaprevir-Pibrentasvir in Non-Cirrhotic Genotype 2 ENDURANCE-2 *ENDURANCE-2: Study Features ENDURANCE-2 Trial Design: Randomized, double-blind, placebo-controlled

More information

HCV-G3: Sofosbuvir with ledipasvir or daclatasvir?

HCV-G3: Sofosbuvir with ledipasvir or daclatasvir? HCV-G3: Sofosbuvir with ledipasvir or daclatasvir? Ioannis Goulis, MD Aristotelian University of Thessaloniki XXIII International Hepatitis B & C Meeting of Athens Hadziyannis HCV genotype 3 therapy Chronic

More information

Addressing Unmet Medical Needs in HCV Genotype 3

Addressing Unmet Medical Needs in HCV Genotype 3 Addressing Unmet Medical Needs in HCV Genotype 3 Karen Doucette, MD, MSc (Epi), FRCPC Associate Professor, Division of Infectious Diseases, Department of Medicine University of Alberta Objectives Identify

More information

10/21/2016. Susanna Naggie, MD, MHS Associate Professor of Medicine Duke University Durham, North Carolina. Learning Objectives

10/21/2016. Susanna Naggie, MD, MHS Associate Professor of Medicine Duke University Durham, North Carolina. Learning Objectives A Crash Course on the AASLD/IDSA Hepatitis C Virus Infection Treatment Guidelines: What s New Susanna Naggie, MD, MHS Associate Professor of Medicine Duke University Durham, North Carolina FORMATTED: 1/3/16

More information

Glecaprevir-Pibrentasvir in HCV GT 1 or 4 & Prior DAA Treatment MAGELLAN-1 (Part 2)

Glecaprevir-Pibrentasvir in HCV GT 1 or 4 & Prior DAA Treatment MAGELLAN-1 (Part 2) Phase 3 Treatment-Experienced in HCV GT 1 or 4 & Prior DAA Treatment MAGELLAN-1 (Part 2) in HCV GT 1 or 4 & Prior DAA Treatment MAGELLAN-1 (Part 2): Study Features MAGELLAN-1 (Part 2) Trial Design: Randomized,

More information

Clinical Criteria for Hepatitis C (HCV) Therapy

Clinical Criteria for Hepatitis C (HCV) Therapy Clinical Criteria for Hepatitis C (HCV) Therapy Pre-Treatment Evaluation o Must have chronic hepatitis C and HCV genotype and sub-genotype documented; o Patients who have prior exposure to DAA therapy

More information

Length of Authorization: 8-12 weeks. Requires PA: All direct-acting antivirals for treatment of Hepatitis C. Approval Criteria

Length of Authorization: 8-12 weeks. Requires PA: All direct-acting antivirals for treatment of Hepatitis C. Approval Criteria Hepatitis C Direct-Acting Antivirals Goals: Approve use of cost-effective treatments supported by the medical evidence. Provide consistent patient evaluations across all hepatitis C treatments. Ensure

More information

VII CURSO AVANCES EN INFECCIÓN VIH Y HEPATITIS VIRALES

VII CURSO AVANCES EN INFECCIÓN VIH Y HEPATITIS VIRALES VII CURSO AVANCES EN INFECCIÓN VIH Y HEPATITIS VIRALES REGIMENES TERAPÊUTICOS DE LA HEPATITIS C, INTERFERÓN FREE A Coruña 2 Febrero 2013 Rui Sarmento e Castro Centro Hospitalar do Porto HJU ECS Universidade

More information

The Dawn of a New Era: Hepatitis C

The Dawn of a New Era: Hepatitis C The Dawn of a New Era: Hepatitis C Naudia L. Jonassaint Assistant Professor of Medicine and Surgery University Pittsburgh School of Medicine December 1, 2015 Objectives After presentation the learner should

More information

Interferon free therapy Are we getting there? Graham R Foster Queen Marys University of London

Interferon free therapy Are we getting there? Graham R Foster Queen Marys University of London Interferon free therapy Are we getting there? Graham R Foster Queen Marys University of London IFN free therapy Disclosures I have received personal and institutional funding from companies that sell drug

More information

Follow-up of patients with SVR Lawrence Serfaty Service d Hépatologie, UMR_S 938 Hôpital Saint-Antoine Université Pierre&Marie Curie Paris, France

Follow-up of patients with SVR Lawrence Serfaty Service d Hépatologie, UMR_S 938 Hôpital Saint-Antoine Université Pierre&Marie Curie Paris, France 9th Paris Hepatitis Conference, January 11-12, 2016 Follow-up of patients with SVR Lawrence Serfaty Service d Hépatologie, UMR_S 938 Hôpital Saint-Antoine Université Pierre&Marie Curie Paris, France Disclosures

More information

SOLAR-1 (Cohorts A and B)

SOLAR-1 (Cohorts A and B) Phase 2 Treatment Naïve and Treatment Experienced Ledipasvir-Sofosbuvir + RBV in HCV GT 1,4 and Advanced Liver Disease SOLAR-1 (Cohorts A and B) Charlton M, al. Gastroenterology. 2015; [Epub ahead of print]

More information

Hepatitis C Agents

Hepatitis C Agents Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.01.41 Subject: Hepatitis C Agents Page: 1 of 20 Last Review Date: March 16, 2018 Hepatitis C Agents Description

More information

Pharmacy Medical Necessity Guidelines: Medications for the Treatment of Hepatitis C

Pharmacy Medical Necessity Guidelines: Medications for the Treatment of Hepatitis C Pharmacy Medical Necessity Guidelines: Medications for the Treatment of Hepatitis C Effective: March 13, 2018 Prior Authorization Required Type of Review Care Management Not Covered Type of Review Clinical

More information

Hepatitis C Agents

Hepatitis C Agents Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.01.41 Subject: Hepatitis C Agents Page: 1 of 19 Last Review Date: December 8, 2017 Hepatitis C Agents

More information

ICVH 2016 Oral Presentation: 28

ICVH 2016 Oral Presentation: 28 Ledipasvir/Sofosbuvir Is Safe and Effective for the Treatment of Patients with Genotype 1 Chronic HCV Infection in Both HCV Mono- and HIV/HCV Coinfected Patients A Luetkemeyer 1, C Cooper 2, P Kwo 3, K

More information

Baseline and acquired viral resistance to DAAs: how to test and manage

Baseline and acquired viral resistance to DAAs: how to test and manage Baseline and acquired viral resistance to DAAs: how to test and manage Round table discussion by Marc Bourliere, Robert Flisiak, Vasily Isakov, Mark Sulkowsky & Konstantin Zhdanov Prevalence of baseline

More information

SASKATCHEWAN FORMULARY BULLETIN Update to the 62nd Edition of the Saskatchewan Formulary

SASKATCHEWAN FORMULARY BULLETIN Update to the 62nd Edition of the Saskatchewan Formulary April 1, 2017 Bulletin #165 ISSN 1923-0761 SASKATCHEWAN FORMULARY BULLETIN Update to the 62nd Edition of the Saskatchewan Formulary Related Information for Prescribers: Only prescribers who have completed

More information

Why make this statement?

Why make this statement? HCV Council 2014 10 clinical practice statements were evaluated by the Council A review of the available literature was conducted The level of support and level of evidence for the statements were discussed

More information

Duncan Webster, BSc, BA, MA, MD, FRCPC

Duncan Webster, BSc, BA, MA, MD, FRCPC Moderator Duncan Webster, BSc, BA, MA, MD, FRCPC Internist, Infectious Disease Physician, Department of Medicine Medical Microbiologist, Department of Laboratory Medicine, Saint John Regional Hospital

More information

HIV/Hepatitis C in France: data from real life cohorts LIONEL PIROTH CHU DIJON UNIVERSITY OF BURGUNDY DECEMBER LONDON

HIV/Hepatitis C in France: data from real life cohorts LIONEL PIROTH CHU DIJON UNIVERSITY OF BURGUNDY DECEMBER LONDON HIV/Hepatitis C in France: data from real life cohorts LIONEL PIROTH CHU DIJON UNIVERSITY OF BURGUNDY DECEMBER 2015 - LONDON The need Decreasing prevalence of chronic hepatitis C in French people living

More information

The Changing World of Hepatitis C

The Changing World of Hepatitis C The Changing World of Hepatitis C Alnoor Ramji Gastroenterology & Hepatology Clinical Associate Professor Division of Gastroenterology University Of British Columbia St. Paul s Hospital Site Disclosures

More information

Glecaprevir-Pibrentasvir in Cirrhotic Genotype 1, 2, 4, 5, and 6 EXPEDITION-1

Glecaprevir-Pibrentasvir in Cirrhotic Genotype 1, 2, 4, 5, and 6 EXPEDITION-1 Phase 3 Treatment-Naïve and Treatment-Experienced Glecaprevir-Pibrentasvir in Cirrhotic Genotype 1, 2, 4, 5, and 6 EXPEDITION-1 EXPEDITION-1: Study Features EXPEDITION-1 Trial Design: Open-label, single-arm,

More information

Supplementary Material*

Supplementary Material* Supplementary Material* Najafzadeh M, Andersson K, Shrank WH, Krumme AA, Matlin OS, Brennan T, et al. Cost- Effectiveness of Novel Regimens for the Treatment of Hepatitis C Virus. Ann Intern Med. doi:10.7326/m14-1152

More information

Evolution of Therapy in HCV

Evolution of Therapy in HCV Hepatitis C: Update on New Therapies and AASLD 13 David Bernstein, MD, FACP, AGAF, FACP Professor of Medicine Hofstra North Shore-LIJ School of Medicine Evolution of Therapy in HCV 199 1999 1 13 (%) SVR

More information

Experience with pre-transplant antiviral treatment: PEG/RBV and DAA. Xavier Forns, MD Liver Unit Hospital Clínic IDIBAPS and CIBREHD Barcelona

Experience with pre-transplant antiviral treatment: PEG/RBV and DAA. Xavier Forns, MD Liver Unit Hospital Clínic IDIBAPS and CIBREHD Barcelona Experience with pre-transplant antiviral treatment: PEG/RBV and DAA Xavier Forns, MD Liver Unit Hospital Clínic IDIBAPS and CIBREHD Barcelona Interferon-free regimens G1b nulls Asunaprevir (PI) + Daclatasvir

More information

VIRAL LIVER DISEASE. OAG Post DDW Course Westin Prince, Toronto, June 13-14, 2015

VIRAL LIVER DISEASE. OAG Post DDW Course Westin Prince, Toronto, June 13-14, 2015 VIRAL LIVER DISEASE OAG Post DDW Course Westin Prince, Toronto, June 13-14, 2015 Financial Interest Disclosure (over the past 24 months) Dr. Paul Marotta Relationships related to this presentation! Research

More information

Interferon-based and interferon-free new treatment options

Interferon-based and interferon-free new treatment options Interferon-based and interferon-free new treatment options White Nights of Hepatology St. Petersburg, 7. June 2013 Christoph Sarrazin Klinikum der J. W. Goethe-Universität Medizinische Klinik I Frankfurt

More information

Treatment of Hepatitis C with sofosbuvir/ledipasvir (Harvoni )

Treatment of Hepatitis C with sofosbuvir/ledipasvir (Harvoni ) Applies to all products administered or underwritten by Blue Cross and Blue Shield of Louisiana and its subsidiary, HMO Louisiana, Inc.(collectively referred to as the Company ), unless otherwise provided

More information

Treatment of HCV in 2016

Treatment of HCV in 2016 5/1/16 Treatment of HCV in 16 Graham R Foster Professor of Hepatology QMUL Conflicts of Interest Speaker and consultancy fees received from AbbVie, BI, BMS, Gilead, Janssen, Roche, Merck, Novartis, Springbank,

More information

Clinical Criteria for Hepatitis C (HCV) Therapy

Clinical Criteria for Hepatitis C (HCV) Therapy Clinical Criteria for Hepatitis C (HCV) Therapy Pre-Treatment Evaluation o Must have chronic hepatitis C and HCV genotype and sub-genotype documented; o Patients who have prior exposure to DAA therapy

More information

HCV therapy : Clinical case

HCV therapy : Clinical case HCV therapy : Clinical case PHC 2018 Paris January 14th, 2018 Tarik Asselah (MD, PhD) Professor of Medicine Hepatology, Chief INSERM UMR 1149, Hôpital Beaujon, Clichy, France. Disclosures Professor Asselah

More information

THE THERAPEUTIC REVOLUTION THAT TRANSFORMED CHRONIC HEPATITIS C TO A CURABLE DISEASE

THE THERAPEUTIC REVOLUTION THAT TRANSFORMED CHRONIC HEPATITIS C TO A CURABLE DISEASE THE THERAPEUTIC REVOLUTION THAT TRANSFORMED CHRONIC HEPATITIS C TO A CURABLE DISEASE MARIA SCHINA CONSULTANT PHYSICIAN INTERNAL MEDICINE AND HEPATOLOGY ATHENS EUROCLINIC 10 th INTERNATIONAL CONGRESS OF

More information

Need to Assess HCV Resistance to DAAs: Is it Useful and When?

Need to Assess HCV Resistance to DAAs: Is it Useful and When? Need to Assess HCV Resistance to DAAs: Is it Useful and When? Stéphane Chevaliez French National Reference Center for Viral Hepatitis B, C and delta Department of Virology & INSERM U955 Henri Mondor Hospital

More information

Treating HCV After Liver Transplantation: What are the Treatment Options?

Treating HCV After Liver Transplantation: What are the Treatment Options? 4 th OPTIMIZE WORKSHOP USING DAAs IN PATIENTS WITH CIRRHOSIS AND LIVER RECIPIENTS Treating HCV After Liver Transplantation: What are the Treatment Options? Maria Carlota Londoño, MD Liver Unit, Hospital

More information

Future strategies with new DAAs

Future strategies with new DAAs Future strategies with new DAAs Ola Weiland professor New direct antiviral drugs Case no 1 male with genotype 2b Male with gt 2b chronic HCV Male with gt 2b relapse afer peg-ifn + RBV during 24 weeks

More information

Meet the Professor: HIV/HCV Coinfection

Meet the Professor: HIV/HCV Coinfection Meet the Professor: HIV/HCV Coinfection Vincent Lo Re, MD, MSCE Assistant Professor of Medicine and Epidemiology Division of Infectious Diseases Center for Clinical Epidemiology and Biostatistics University

More information

Prior Authorization Guideline

Prior Authorization Guideline Prior Authorization Guideline Guideline Name Sovaldi (sofosbuvir) Formulary UnitedHealthcare Community & State Formulary Note Approval Date 2/19/2014 Revision Date 7/8/2014 1. Indications Drug Name: Sovaldi

More information

Hepatitis C in Special Populations

Hepatitis C in Special Populations Hepatitis C in Special Populations David E. Bernstein, MD, FACG Vice Chairman of Medicine for Clinical Trials Chief, Division of Hepatology and Sandra Atlas Bass Center for Liver Diseases Northwell Health

More information