F/C AETC Faculty HIV/HCV Thursday May 8, 2014 | 1:30- 2:30pm (EDT) Facilitator/ Presenter Dushyantha T. Jayaweera, MD, MRCOG (UK), FACP University of Miami Case Discussant Patrick Marsh, MD University of South Florida Maribel Gonzalez, RN, ARNP University of South Florida
HIV Case Conference: Highlights from EASL Dushyantha T. Jayaweera MD, MRCOG (UK), FACP Associate Vice Provost for Human Subject Research & Professor of Medicine, University of Miami, Miller School of Medicine, Division of Infectious Diseases Faculty Member, Florida/Caribbean AIDS Education and Training Center
HCV TREATMENT IN TREATMENT NAIVE PATIENTS
SAPPHIRE-I Study: Design ABT-450/r/ABT-267 qd + ABT-333 bid + RBV bid (n=473) ABT-450/r/ABT-267 qd + ABT-333 bid + RBV bid (n=473) Placebo*(n=158)Placebo*(n=158) Week ABT-450/r/ABT-267 qd + ABT-333 bid + RBV bid (n=158) ABT-450/r/ABT-267 qd + ABT-333 bid + RBV bid (n=158) Double-Blind Open-Label Feld J, et al. 49th EASL; London, England; April 9-13, Abst. O60. Phase 3 Study Double-Blind Key eligibility criteria HCV genotype 1 Treatment-naïve No cirrhosis No HIV or HBV
SAPPHIRE-1 Study: Interim Results Virologic relapse: 1.7% 3D regimen + RBV was well-tolerated Discontinuations due to adverse events: 0.6% Most commonly reported adverse events Fatigue Headache Nausea Feld J, et al. 49th EASL; London, England; April 9-13, Abst. O60. Patients (Percentage) SVR12 Rates 3D Regimen + RBV 1a (n=322) 1b (n=151) Overall (n=473) 95% 98% 96% Genotype
ABT-450/r/ABT-267 qd + ABT-333 bid+ RBV bid (n=210) ABT-450/r/ABT-267 qd + ABT-333 bid+ RBV Placebo (n=209) Week Phase 3 Study Double-Blind Placebo-controlled Key eligibility criteria HCV genotype 1 Treatment-naïve No cirrhosis No HIV or HBV PEARL-III Study: Design Ferenci P, et al. 49th EASL; London, England; April 9-13, Abst. P1299.
Pearl-III Study: SVR12 and Virologic Failure Rates 3D Regimen + RBV Ferenci P, et al. 49th EASL; London, England; April 9-13, Abst. P1299. Patients (Percentage) No RBV (n=209) With RBV (n=210) 99% SVR12 0% No RBV (n=209) 0.5% With RBV (n=210) Virologic Failure
Pearl-III Study: Safety Results 3D regimen + RBV was well tolerated Discontinuations due to adverse events With RBV: 0% No RBV: 0% Most commonly reported adverse events Headache Fatigue Ferenci P, et al. 49th EASL; London, England; April 9-13, Abst. P1299.
ION-1 Study: Design GT 1 HCV treatment-naïve patients in Europe and USA Broad inclusion criteria Targeted 20% enrollment of patients with cirrhosis No upper age or BMI limit Platelet count ≥50,000/mm 3, no neutrophil minimum 865 patients randomized 1:1:1:1 across four arms Stratified by HCV subtype (1a or 1b) and cirrhosis Mangia A, et al. 49th EASL; London, England; April 9-13, Abst. O164. Wk 0 Wk 12Wk 36Wk 24 LDV/SOF SVR12 LDV/SOF + RBV LDV/SOF LDV/SOF + RBV SVR12
179/18032/34178/18433/33181/18431/33179/18136/36 12 Weeks24 Weeks LDV/SOF + RBV LDV/SOF SVR12 (Percentage) Absence of Cirrhosis Cirrhosis ION-1 Study: SVR12 - Absence of Cirrhosis vs Cirrhosis Error bars represent 95% confidence intervals. Mangia A, et al. 49th EASL; London, England; April 9-13, Abst. O164.
179/18032/34178/18433/33181/18431/33179/18136/36 12 Weeks24 Weeks LDV/SOF + RBV LDV/SOF SVR12 (Percentage) Absence of CirrhosisCirrhosis ION-1 Study: SVR12 - Absence of Cirrhosis vs Cirrhosis Error bars represent 95% confidence intervals. Mangia A, et al. 49th EASL; London, England; April 9-13, Abst. O164.
ION-3 Study: Design GT 1 treatment-naïve patients without cirrhosis Broad inclusion criteria No upper age or BMI limit Opiate substitution therapy allowed 647 patients randomized 1:1:1 across three arms Stratified by HCV subtype (1a or 1b) LDV/SOF LDV/SOF + RBV SVR12 Kowdley K, et al. 49th EASL; London, England; April 9-13, Abst. O56. Wk 0 Wk 12Wk 36Wk 24
Error bars represent 95% confidence intervals. Kowdley K, et al. 49th EASL; London, England; April 9-13, Abst. O56. ION-3 Study Results – Non-Inferiority Comparison 201/216202/215206/216 p= Weeks12 Weeks LDV/SOF + RBVLDV/SOF SVR12 (Percentage)
Study Design: MK-5172 (100 mg QD) + MK-8742 (50 mg QD) ± RBV in 253 Pte n = 31 Follow-up D1TW12SVR12TW4TW8 TN + Cirrhosis n=123 TN + Cirrhosis n=123 PR-Nulls ± Cirrhosis n=130 PR-Nulls ± Cirrhosis n=130 SVR24TW18FU8FU4 Follow-up No RBV + RBV No RBV + RBV No RBV + RBV Follow-up n = 29 n = 32 n = 31 n = 32 n = 33 n = 32 Lawitz E, et al. 49th EASL; London, England; April 9-13, Abst. O61. No RBV + RBV No RBV + RBV No RBV + RBV
* 30 31* TW4 TW12 FU4/8 Breakthrough Relapse Discontinuation Efficacy of MK MK-8742 ± RBV in Treat-Naïve Pte + Cirrhosis:12W vs18W *Excludes patients who have not yet reached the FU4 time point 12 week arms include 97% of FU8 results Lawitz E, et al. 49th EASL; London, England; April 9-13, Abst. O61.
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