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Learning Objectives Review clinical advances for treating special populations of patients with HCV, including those with renal impairment and other comorbidities. Describe emerging clinical considerations underlying the management of HCV. Evaluate the safety, efficacy, and recommended usage of recently-approved and emerging direct-acting antiviral (DAA) agents for the management of HCV. Agenda Emerging Clinical Considerations Toward a Cure for All Patient Populations An Update on Recently-approved and Emerging DAA Regimens 15 Vindico Medical Education
Subpopulation Emerging Clinical Considerations Norah Terrault, MD, MPH Professor of Clinical Medicine and Surgery University of California, San Francisco Director of Viral Hepatitis Research in Liver Transplantation Department of Gastroenterology/Hepatology University of California, San Francisco San Francisco, CA HCV-TARGET: SVR1 and Relapse Rates for LDV/SOF ± RBV by Treatment Duration in HCV G1 Patients 1 LDV/SOF 97 97 95 SVR Relapse 1 LDV/SOFRBV 97 9 8 8 4 4 5 15/154 4/154 7/7 /7 15/11 8/11 8 Weeks 1 Weeks 4 Weeks Terrault N, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract 94. 8 1 8/89 1/89 1/1 1/1 1 Weeks 4 Weeks SVR1: SVR at 1 (±1) weeks post treatment HCV-TARGET: SVR1 with LDV/SOF Therapy by Subgroups All Cirrhotic Non-cirrhotic HCV<1 mln HCV>=1 mln Genotype 1a Genotype 1b Geno 1a Cirrhotic Geno 1b Cirrhotic Naïve Experienced No Prior OLT Prior OLT Decompensated Non-decompensated No baseline PPI Baseline PPI 4 8 1 SVR1 LCL (95%) UCL (95%) rate (%) 95.1 9.5 97. 89.9 9. 95.7 9.8 98.1 99 95. 97.5 98.9 94 95.9 97. 94. 9.1 97.4 94.5 97. 98.9 87.4 91.9 95.1 88.5 95.9 99.1 9.5 95. 97.1 95.7 97.7 98.9 95. 9.9 97.9 79.5 9 9. 8.1 87.9 9.4 9. 97. 98.5 9. 97. 98. 89.5 9. 9.1 SVR Rate (%) Completed treatment as of 7/1/15 and have available virological outcomes. Patients who discontinued due to AE or were lost to follow-up are excluded. SVR1: SVR at 1 (±1) weeks post treatment Includes patients receiving 8 (n=154), 1 (n=7), 4 (n=11) and other (n=7) week of therapy Terrault N, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract 94. 15 Vindico Medical Education
SVR Rates (%) SVR1, % TRIO: SVR1 Rates by Regimen 1% 94% 97% 78% 91% 9% 8% 7% % 5% 4% % % 1% 14/151 74/7 /41 4/47 % LDV-SOF LDV-SOF SMVSOF D RBV /-RBV /-RBV Relapse 44 Relapse Relapse 5 Relapse Death Death Death Death LTFU LTFU 1 LTFU 4 LTFU 1 DC 9 DC 1 DC DC 1 Afdhal NH, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract LB-17. ombitasvir/paritaprevir/ritonavir dasabuvir (D) TRIO: 149 Patients Were Treated Outside of FDA Guidelines and Saw a Significantly Lower SVR Rate (84% SVR Outside vs 95% SVR Inside) Inside vs Outside FDA Guidelines LDV-SOF /-RBV D /-RBV SMVSOF /-RBV Total Outside FDA Guidelines Inside FDA Guidelines 85% (115/15) 95% (191/14) Total 94% (15/1597) 8% (5/) 9% (8/41) 91% (4/47) % (5/8) 8% (7/) 78% (/41) 84% (15/149) 95% (145/15) 94% (1581/185) *Patients outside of guidelines: GT1a on D without RBV, tx failure cirrhotic patients on 1 weeks of D/-RBV, LDV-SOF without RBV, or SMVSOF/-RBV ombitasvir/paritaprevir/ritonavir dasabuvir (D) Afdhal NH, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract LB-17. VA s National HCV Clinical Case Registry SVR Rates: Treatment Naïve, GT1 1 9 8 LDV/SOF * * LDV/SOFRBV * 7 5 4 1 87/ 47/ 145/ 14/ 15 5/ 8/ 41/ 15/ / 1/ / 74/ 4/ 4/ 74/ 17 514 118 14 /148 89 1 5 57 19 89 9 4 8 D<15 Overall African-America Caucasian FIB-4.5 FIB-4 >.5 UD D 15 No significant differences in unadjusted SVR rates based on age, sex, decompensated liver disease, diabetes, HIV coinfection, BMI, baseline HCV RNA, subtype and IL8B polymorphism. P<.1 *P<.1 Backus LI, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract 9. Week 4 On Treatment HCV RNA 15 Vindico Medical Education
SVR1 (%) SVR1 (%) Rapid Response from San Francisco: NS5A Resistance Testing and Management Considerations Efficacy of LDV-SOF in Patients With and Without NS5A RAVs at Baseline With RAVs No RAVs Without cirrhosis 1 1 98 99 99 99 99 9 8 4 / 17/18 187/189 54/59 79/88 98/ LDV/SOF 8 Weeks LDV/SOF 1 Weeks LDV/SOF 1 Weeks TN < M TN TE Zeuzem S, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract 91. TE, treatment-experienced TN, treatment-naïve Efficacy of LDV-SOF in Patients With and Without NS5A RAVs at Baseline With cirrhosis With RAVs Treatment Naïve No RAVs Treatment Experience With RAVs No RAVs 1 9 9 1 1 1 88 1 9 89 87 1 8 8 4 4 /7 5/8 1/1 7/7 8/9 19/19 LDV/SOF LDV/SOFRBV LDV/SOF LDV/SOFRBV LDV/SOF 1 weeks 4 weeks 1 weeks 4 weeks The largest impact of RAVs on treatment outcome was observed in patients with cirrhosis treated for 4 weeks of LDV/SOF (and no ribavirin) Zeuzem S, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract 91. 15 Vindico Medical Education
Integrated Analysis of the Prevalence and Impact of Baseline NS5A RAVs in Patients Treated with EBR-GZR GT1a: Population Sequencing Prevalence of NS5A RAVs = % EBR RAVs=~5% TN/relapsers EBR RAVs=~1% if TE non-responders GT1b: minimal impact of baseline EBR RAVs 1 8 ERB RAVs 1% No RAVs: 1/8 (9%) 97% 9% NS5A Class RAVs 1% No RAVs: 54/8 (79%) 9% 4% 1 8 ERB RAVs NS5A Class RAVs % 15% No RAVs: No RAVs: 51/5 44/5 (98%) (85%) 1% 1% 1% 1% 4 4 59 5 9 51 1 44 8 1 7 54 14 51 1 44 8 EBR RAVs NS5A Class RAVs EBR RAVs NS5A Class RAVs Jacobson IM, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract LB-. 1 weeks EBR/GZR 1/18 weeks EBR/GZR RBV Toward a Cure for All Patient Populations Mark Sulkowski, MD Professor of Medicine, Medical Director of the Viral Hepatitis Center Johns Hopkins School of Medicine Baltimore, MD Retreatment with SOF and SMV of Patients Who Previously Failed on an HCV NS5A Inhibitor containing Regimen Week Week 1 Week 4 DCV failures SMV/SOF SVR1 N=1 Baseline characteristics N=1 Mean age, y (range) 54 (4 7) Male, n (%) 1 (81) G1a, n (%) 11 (9) G1b, n (%) () G4, n (%) (1) Median HCV RNA, 1 IU/mL 1.8 HCV RNA >8,, IU/mL, n (%) 14 (88) Severe fibrosis (FS 9. 1.5 kpa), n (%) 7 (44) Cirrhosis (FS>1.5 kpa), n (%) 9 (5) Median time between DCV-based (1 5) regimen and SMV/SOF, m (range) Presence of NS5A RAVs 1 (81) SVR1 According to Fibrosis Stage 1 1 87 8 75 4 1/15* 7/7 /8* Total No cirrhosis Cirrhosis SVR1 According to Genotype 1 1 87 8 Presence of NS RAVs 8 (57)* 4 Prior HCV treatment, n (%) 1 (81) DCV/PR (19) DCV/ASV/PR 1/15* 8/1* / / *Available in 14 patients Total G1a G1b G4 *1 patient did not reach Week 1 FU Hezode C, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract 11. 1 8 15 Vindico Medical Education
Retreatment With SOF and SMV of Patients Who Previously Failed on an HCV NS5A Inhibitor containing Regimen Efficacy according to on-treatment response Rapid response n=1 Early response n-1 Late response n=5 (%) (%) (1%) 7 7 7 SVR1: 9/9* SVR1: 1/1 SVR1: /5 5 5 5 <1 IUmL not detected: n= 4 4 4 or <1 IUmL detected: n=5 or HCV RNA<1 IUmL HCV RNA<1 IUmL >1 IUmL: n= detected or not detected or not 1 1 1 4 8 EOT SVR4 4 8 EOT SVR4 4 8 EOT SVR4 1 patient does not reach week-1 follow-up visit Abbot RealTime HCV assay was used Hezode C, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract 11. Treatment failure cases (n=) Patient 1 Patient Gender Female Male Age 47 48 G 1a 1a Cirrhosis Yes Yes (FS.8 kpa) (FS 14.9 kpa) Albumin 4.5 Platelets 7,, Prior tx DCV/PR DCV/ASV/PR On-tx Slow Slow response BL HCV RNA,84,1,9,157 IU/mL BL NS RAVs R155K Q8K, V17I BL NS5A M8T L1M RAVs SMV SOF was highly effective in this NS5A inhibitor-exposed population Treatment extension beyond 1 weeks and/or the addition of RBV in most difficult to cure? QUARTZ-I: Retreatment of HCV G1 DAA Failures With OBV/PTV/r DSV SOF Phase, multicenter study Open-label treatment G1a No cirrhosis OBV/PTV/r DSV N=14 SOF RBV G1a Cirrhosis OBV/PTV/r DSV SOF RBV N= G1b N= OBV/PTV/r DSV SOF 1 4 7 G1b G1a OBV/PTV/r G1a OBV/PTV/r OBV/PTV/r Characteristic DSV SOF RBV DSV SOF RBV DSV SOF RBV 1 weeks, n=14 4 weeks, n= 1 weeks, n= Male, n (%) 8 (57) (1) 1 (5) Age, median years 59 (41 5) (54 4) 1 (59 ) BMI, median. (17.8.4).8 (.8 5.9) 1.4 (.7.) HCV RNA median log 1. (. 7.).55 (5.1 7.45).9 (.5.) IU/mL IL8B non-cc, n (%) 1 (71) (1) (1) Fibrosis stage, n (%) F 1 (4) 1 (5) F () F (15) 1 (17) 1 (5) F4 (15) 5 (9) TE prior to previous 4 (9) (5) DAA, n (%) DAA-experienced pts G1 were enrolled, including with G1a and with compensated cirrhosis Characteristic cont. Relapse, n (%) Breakthrough, (%) Prior DAA regimen OBV/PTV/r OBV/PTV/r DSV SMV SOF SMV SAM RBV SOF RBV SOF PR TPV PR RAVs NS-Q8K NS-D18E/V NS5A-M8I/V NS5A-QE/H/R NS5A-L1M NS5A-H58D NS5A-Y9C/F/H NS5B-S55G NS5B-M414I/T NS5B-Y448H G1a OBV/PTV/r DSV SOF RBV 1 weeks, n=14 11 (79) (1) (14) 8 (57) 1 (7) 1 (7) (14) 9 (4) (14) 8 (57) 7 (5) (14) 4 (9) (14) 1 (7) G1a OBV/PTV/r DSV SOF RBV 4 weeks, n= (1) (1) 5 (8) 1 (17) () 1 (17) () G1b OBV/PTV/r DSV SOF RBV 1 weeks, n= 1 (5) 1 (5) 1 (5) 1 (5) 1 (5) 1 (5) 1 (5) Poordad F, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract LB-. QUARTZ-I: Retreatment of HCV G1 DAA Failures With OBV/PTV/r DSV SOF 1 9 8 7 5 4 1 Virologic Response During and After Treatment 95 1 1 1 1 1 1 1 1 1 1 1 9 9 9 14 15 1 14 14 14 14 14 1 1 1 At baseline, 17/ patients had at least 1 RAV in 1 of the DAA targets, while the remaining 5 had Q8K in NS, but no other RAVs present 7 patients had RAVs (other than NS Q8K) in targets patients had RAVs in all targets Overall HCV G1a HCV G1a HCV G1b No cirrhosis Cirrhosis These findings suggest that a multi-targeted treatment regimen can achieve high response rates in prior DAA failures, including those who previously failed D therapy, as well as those with persistent NS5A RAVs Poordad F, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract LB-. 15 Vindico Medical Education
% of Patients with Positive Urine Drug Screen % SVR1 (95% Cl) % of Patients with Positive Urine Drug Screen C-EDGE CO-STAR: Efficacy of Grazoprevir and Elbasvir in Persons Who Inject Drugs (PWID) Receiving Opioid Agonist Therapy Phase, randomized, parallel-group, placebo-controlled, double-blind trial Treatment naïve, GT1, 4, ; mixed genotypes of 1, 4, and allowed On opiate agonist therapy (OAT) for at least months, and consistently kept at least 8% of scheduled therapy appointments while on OAT Goal of % with cirrhosis and may be co-infected with HIV Immediate Treatment Arm EBR/GZR, n=1 Unblinding Follow-up for 4 weeks Deferred Treatment Arm Placebo, n=1 Unblinding EBR/GZR Follow-up for 4 weeks Dore G, et al. Presented at: AASLD 15; November 1-17; San Francisco, D1 W4 W8 W1 W1 W W8 W W5 CA. Abstract 4. C-EDGE CO-STAR: SVR 1 in the Immediate Treatment Group Modified Full Analysis Set (mfas) 9.1 9. 95.5 1 1 8 4 All GT GT1a* GT1b GT4 GT 189/198 147/15 8/9 11/11 /5 Failures Relapse 7 4 1 Discontinuation Reinfection counted as success 5 LTFU or discontinued unrelated to Virologic Failure excluded from mfas analysis 1 1 1 *Includes one subject with mixed infection (GT1 and GT1b) who achieved SVR1 Dore G, et al. Presented at: AASLD 15; November 1-17; San Francisco, CA. Abstract 4. 7 5 4 Urine Drug Screen Results: Day 1 to Treatment Week 1 Immediate Treatment Arm; EBR/GZR Treatment Phase Any drug use of 8 classes* Any drug use of 7 classes (excl. cannabinoids) Cannabinoids Benzodiazepines Opiates 7 5 4 Deferred Treatment Arm; Placebo Phase *8 drug classes: amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates, phencyclidine, propoxyphene 1 Cocaine 1 Day 1 TW1 TW TW4 Tw TW8 TW1TW1 Time Point Amphetamines Day 1 TW1 TW TW4 Tw TW8 TW1 TW1 Time Point Time point of Demographics Fibrosis Stage GT at baseline UDS at baseline* UDS at TW1* GT at Follow-up detectable HCV RNA 48 yo Asian male NC 1a BZP, OPA BZP FW8 a yo white female NC 1a AMP,OPA FW8 1a 55 yo white female C 1a BZP, OPA BZP, OPA FW8 a 45 yo Asian male NC a OPA FW8 1b 7 yo Asian female NC a AMP, BZP, OPA AMP, BZP, OPA FW8 a Dore G, et al. Presented at: AASLD 15; November 1-17; San Francisco, CA. Abstract 4. C-EDGE CO-STAR 15 Vindico Medical Education
Patients, % Change from baseline (g/dl) C-EDGE Co-Infected: Phase Study of Elbasvir/Grazoprevir in Patients with HIV/HCV SVR4: Modified Full Analysis Set 1% 97.% 97.1% 1% 9.% 75% 5% 5% % All Patients GT1a GT1b GT4 All GT GT1a GT1b GT4 15/19 4/4 /7 /8 (97.%) (97.1%) (1%) (9.%) Relapse 5 4 1 Excluded Reinfection 1 1 LTFU or discontinued 8 5 1 unrelated to VF Rockstroh JK, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract 1. SLAM C Randomized Open Label Prospective Clinical Pilot Study Interim Data: SOF LDV vs SOF SMV Combination Therapy in the Management of Acute HCV 9 patients with acute HCV SOF/LDV for 4 weeks (n=14) SOF/SMV for 8 weeks (n=15) Group A n=14 Group B n=15 Baseline characteristics SOF LDV SOF SMV Duration of therapy, weeks 4 8 Age, range (median) 18 9 (7) 4 (1) M:F 1. 14.1 BMI, %. 4. Caucasians Hispanic African American 9 1 Asian G1a 7 7 G1b 7 8 Mean viral load, k 1, 1, IL8b CC 4 IL8b CT 4 IL8b TT 9 Pre-Q8K (all G1a) Pre-5A polymorphism Post-Q8K (no changes) (no changes) Post-5A RAVs 1 Basu P, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract 174. Undetectable Group A n=14 SOF LDV 4 weeks therapy Group B n=15 SOF SMV 8 weeks therapy Day 7, n, % 1/14, 9.9% 1/15, 9.% 4 weeks, n, % 14/14, 1% (ETVR) 14/15, 9.% (1 dropped, started IV drug use) 8 weeks, n, % 14/14, 1% 14/15, 9.% (ETVR) 1 weeks, n, % 14/14, 1% SVR1 14/15, 9.% weeks, n, % (per protocol) 1 dropped, 1/1, 1% SVR1 transferred to prison) (1 was LTFU homeless) Retention 1/14, 9.9% 1/15, 9.% Short course all oral therapy may be effective in acute HCV RUBY-I: Safety of OMB/PTV/RTV DSV for Treating HCV G1 Infection in Patients With Severe Renal Impairment or End-stage Renal Disease D ± RBV N= Male, n (%) 17 (85) Black, n (%) 14 (7) Age, years; median (range) (49 9) Hispanic or Latino ethnicity, n (%) (15) Degree of fibrosis, n (%) F F1 1 (5) F () F 4 () HCV VL, log 1 (IU/mL);. (5.5 7.) median (range) G1a, n (%) 1 (5) Hemoglobin, g/dl; mean (SD) 1. (1.8) CKD stage, n (%) 4 (egfr 15 ml/min/1.7m ) 8 (4) 5 (egfr <15 ml/min/1.7m or dialysis) 1 () On dialysis, n (%) 1 (5) egfr, ml/min/1.7m ; 1.9 (5.4 9.9) median (range) Creatinine, mg/dl; median (range). (. 1.8) Hb change with D ± RBV mg/day 1-1 - - BL W1WWW4 W W8 W1/EOT PTW4 G1b (DAA only) G1a (DAA RBV)* *8 of 14 patients held RBV Pockros PJ. Presented at: EASL 15; April -; Vienna, Austria. Abstract LO1. Pockros PJ, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract 19. 15 Vindico Medical Education
% Patients SVR1 (%) RUBY-I: OMB/PTV/RTV DSV for Treating HCV G1 Infection in Patients With Severe Renal Impairment or End-stage Renal Disease 1 8 95 ITT Virologic Response, N= 1 9 9 4 19 18 18 RVR EOTR SVR4 SVR1 Pockros PJ, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract 19. An Update on Recently-approved and Emerging DAA Regimens K. Rajender Reddy, MD Professor of Medicine Professor of Medicine in Surgery Director of Hepatology Director, Viral Hepatitis Center University of Pennsylvania Philadelphia, PA The ASTRAL Trials: ASTRAL-1, SOF/VEL SOF/VEL (4 mg/1 mg) 1 Weeks ASTRAL-1 ASTRAL- ASTRAL- ASTRAL-4 GT 1,, 4 GT GT GT 1 CPT-B Cirrhosis Sofosbuvir (SOF); Nucleotide polymerase inhibitor Velpatasvir (VEL; GS-581); NS5A inhibitor SOF/VEL FDC: Once daily, oral, FDC (4/1 mg) 1 8 ASTRAL-1: SVR1 by Genotype 99 98 99 1 1 97 1 Feld JJ, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract LB-. Feld JJ, et al. N Engl J Med. 15 [epub ahead of print]. Sulkowski MS, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract 5. Mangia A, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract 49. Charlton MR, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract LB-1. 4 1 relapse 1 relapse 1 death lost to follow-up 1 withdrew consent 18 117 14 11 4 41 4 1 118 14 11 5 41 Total 1a 1b 4 5 Error bars represent 95% confidence intervals. Genotype Feld JJ, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract LB-. Feld JJ, et al. N Engl J Med. 15 [epub ahead of print]. 15 Vindico Medical Education
SVR1 (%) HCV RNA < LLOQ TD/TND (%) SVR1 (%) HCV RNA < LLOQ TD/TND (%) ASTRAL-: Genotype Treatment-naïve and Treatment-experienced Genotype HCV-infected patients, with and without Cirrhosis P=.18* 1 99 94 8 4 1/14 14/1 SOF/VEL SOF RBV * P value for superiority of SOF/VEL compared with SOFRBV Error bars represent 95% confidence intervals. Sulkowski MS, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract 5. ASTRAL-: SVR1 by Cirrhosis or Treatment History 1 97 87 SOF/VEL 91 SOF RBV 97 8 9 8 7 relapses relapses 7 relapses 1 non-response 4 other relapses other 4 relapses 1 relapses 4 relapses 15 relapses other 8 other other 1 other 191 1 7 55 17 4 45 197 187 8 8 4 71 71 No Yes Naïve Experienced Error bars represent 95% confidence intervals. Cirrhosis Status Treatment History Mangia A, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract 49. ALLY- Study: Daclatasvir Plus Sofosbuvir Plus Ribavirin for 1 or 1 Weeks in HCV Genotype -Infected Patients With Advanced Fibrosis or Cirrhosis Phase Study SVR1: All Treated Patients 1 9 8 7 5 4 1 ITT ANALYSIS (Primary Endpoint) 9 88 9 45 5 1 4 Overall 1 Weeks 1 Weeks VBT a Relapse b 4 Death c 1 1 4 a VBT (virologic breakthrough}: confirmed HCV RNA 1 log 1 IU/mL above nadir, or LLOQ if previously < LLOQ TD or TND; b Relapse: confirmed HCV RNA LLOQ at any posttreatment visit following < LLOQ TND at end of treatment; c Dilated cardiomyopathy on Day 7, not related to treatment. 1 9 8 7 5 4 1 9 45 49 OBSERVED ANALYSIS 91 9 1 4 Overall 1 Weeks 1 Weeks VBT a Relapse b 4 Leroy V, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract LB-. 15 Vindico Medical Education
SVR1 (%) SVR 1, % Patients SVR1, % Patients ASTRAL-4: GT 1- Treatment-naïve or -experienced Patients with CPT B Cirrhosis Overall SVR1 1 8 94 8 8 4 75/9 SOF/VEL 1 week 8/87 77/9 SOF/VEL RBV SOF/VEL 1 week 4 week P value <.1 for comparison of SVR1 rate to 1% for each treatment group Charlton MR, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract LB-1. SURVEYOR-I: HCV GT1 Non-Cirrhotic Treatment-naïve or -experienced Patients With ABT-49 and ABT-5 for 8 Weeks SURVEYOR-I Part 1: ITT SVR1 Rates ABT-49: pangenotypic HCV NS/4A protease inhibitor ABT-5: pangenotypic HCV NS5A inhibitor PT Week 4 Day 1 Week 1 Treatment period Post-treatment (PT) period n=9 ABT-49 mg ABT-5 4 mg 1 8 4 97 1 n=4 ABT-49 mg ABT-5 1 mg 1% (9/9) treatment-experienced patients achieved SVR1 98% (49/5) treatment-naïve patients achieved SVR1 ABT-49 ABT-5 8 9 mg 4 mg 4 4 mg 1 mg Poordad F, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract LB-14. SURVEYOR-II: ABT-49 and ABT-5 In Non-cirrhotic Treatment-naïve and Treatment-experienced Patients With HCV Genotype Day 1 Week 1 PT Week 4 Treatment period Post-treatment (PT) period n= ABT-49 mg ABT-5 1 mg n= a ABT-49 mg ABT-5 1 mg ITT SVR1 Rates by Treatment 9 9 94 1 8 8 n=1 ABT-49 mg ABT-5 1 mg RBV b n= ABT-49 mg ABT-5 4 mg 4 N=11. a Includes one patient who was incorrectly assigned to treatment in the GT cohort. b Daily dose of 1 mg or 1 mg RBV dosed BID based on patient body weight being <75 kg or 75 kg. open-label, multicenter Phase trial 8 8 9 1 5 ABT-49 ABT-5 mg 1 mg mg 1 mg mg 1 mg RBV mg 4 mg Kwo PY, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract 48. 15 Vindico Medical Education
SVR1 (%) Patients, % ± Compensated Cirrhotic Patients With HCV GT 1, 4 or Infection Treated With Grazoprevir/Elbasvir: An Integrated Analysis 1 SVR1 Treatment Naïve Treatment Experienced Full analysis set 97.8 9. 88.9 91.4 9.9 1 75 5 5 15 8 48 74 4 49 18 1 54 81 49 49 No RBV RBV No RBV RBV No RBV RBV 1 weeks 1 weeks 1 or 18 weeks LTFU/Early Discon. 1 * 1 98.5% 9.% 9.% 9.5% 9.9% 1.% SVR1 (mfas ) (15/17) (8/1) (48/5) (74/8) (4/49) (49/49) Breakthrough 1 1 Rebound Relapse 1 4 1 *Death (coronary artery disease) Death (lymphoma) n=1;discontinued due to noncompliance, n=1 mfas (modified full analysis set) excludes patients who discontinued treatment for reasons unrelated to study medication. Death (motor vehicle accident) D/C Due to Lab: ALT with increased eosinophils (8.8%) Jacobson IM, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract 4. C-CREST 1 & : Efficacy and Safety of Grazoprevir and MK-8 with Either Elbasvir or MK-848 in Patients with Chronic HCV GT1, or Phase, Randomized, Open-label clinical trials AIMS Part A of C-CREST 1 (GT1 and GT) and C-CREST (GT): Evaluated safety and efficacy of 8 weeks in treatment-naïve, noncirrhotic patients, using combinations of direct-acting antiviral drugs: 1. Grazoprevir (GZR), an NS/4A protease inhibitor. MK-8, an NS5B polymerase inhibitor. Elbasvir (EBR) or MK-848, NS5A inhibitors To select the regimen to be used in Part B of C-CREST 1 and, which will expand treatment into harder-to-treat patient populations Gane EJ, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract LB-15. 8 Week Regimen of GZR/MK-848/MK-8 (45 mg) Achieve High SVR1 Rates in GT1, GT & GT Compared to Prior 1-Week Regimens 1 Weeks GZR/EBR=RBV 8 Weeks GZR/MK-848/MK-8 ( mg) 8 Weeks GZR/MK-848/MK-8 (45 mg) 1 95 1 91 94 95 91 8 8 71 45 4 7* 4 1 4 1 15 9 88 4 14 1 1 GT1 GT GT *Zeuzem S, et al. Ann Intern Med. 15;1:1-1. Brown A, et al. Poster presented at: EASL 15; April -, 15; Vienna, Austria. Poster P771. Gane E, et al. Poster presented at: EASL 15; April -, 15; Vienna, Austria. Poster P77. Gane EJ, et al. Presented at: AASLD 15; November 1-17, 15; San Francisco, CA. Abstract LB-15. C-CREST 15 Vindico Medical Education
Conclusions Thank you for participating Please complete the post test and evaluation to receive your CME credits 15 Vindico Medical Education