Sofosbuvir-Velpatasvir-Voxilaprevir in GT 3 and Cirrhosis POLARIS-3

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Presentation transcript:

Sofosbuvir-Velpatasvir-Voxilaprevir in GT 3 and Cirrhosis POLARIS-3 Phase 3 Treatment Naïve and Experienced Sofosbuvir-Velpatasvir-Voxilaprevir in GT 3 and Cirrhosis POLARIS-3 Jacobson IM, et al. Gastroenterology. 2017;153:113-22.

Sofosbuvir-Velpatasvir-Voxilaprevir in GT 3 and Cirrhosis POLARIS-3: Study Features POLARIS-3 Trial Design: Open-label, randomized, phase 3 trial to compare efficacy of a fixed-dose combination of sofosbuvir-velpatasvir-voxilaprevir for 8 weeks versus sofosbuvir-velpatasvir for 12 weeks in patients with HCV genotype 3 and cirrhosis who were DAA-naïve Setting: 84 sites in United States, Canada, New Zealand, Australia, France, Germany, and United Kingdom Entry Criteria - Age ≥18 years - Chronic HCV GT 3 with compensated cirrhosis - HCV RNA ≥10,000 IU/mL at screening - No prior treatment with DAA; prior peginterferon plus ribavirin allowed Primary End-Point: SVR12 Source: Jacobson IM, et al. Gastroenterology. 2017;153:113-22.

Sofosbuvir-Velpatasvir-Voxilaprevir in GT 3 and Cirrhosis POLARIS-3: Study Design Week 24 8 12 20 GT 3 Cirrhotic DAA Naïve n = 110 SOF/VEL/VOX SVR12 n = 109 SOF/VEL SVR12 Abbreviations: SOF = sofosbuvir; VEL = velpatasvir; VOX = voxilaprevir Drug Dosing SOF-VEL-VOX (400/100/100 mg): fixed dose combination; one pill once daily SOF-VEL (400/100 mg): fixed dose combination; one pill once daily Source: Jacobson IM, et al. Gastroenterology. 2017;153:113-22.

Sofosbuvir-Velpatasvir-Voxilaprevir in GT 3 and Cirrhosis POLARIS-3: Baseline Characteristics SOF-VEL-VOX 8 weeks (n = 110) SOF-VEL 12 weeks (n = 109) Age, mean (range) 54 (25-75) 55 (31-69) Male, n (%) 74 (67) 100 (92) White, n (%) 100 (91) 97 (89) Cirrhosis Features Platelets <100 x 103/μL, n (%) Mean Fibroscan (range), kPa 30 (29) 23 (13-75) 21 (19) 22 (13-75) Body mass index, mean, kg/m2 (range) 28 (20-50) 27 (18-46) Mean HCV RNA, log10 IU/mL (range) 6.0 (1.6-7.6) 6.3 (4.1-7.5) IL28B CC, n (%) 41 (37) 52 (48) Source: Jacobson IM, et al. Gastroenterology. 2017;153:113-22.

Sofosbuvir-Velpatasvir-Voxilaprevir in GT 3 and Cirrhosis POLARIS-3: Baseline Characteristics Information on Prior Treatment SOF-VEL-VOX x 8 weeks (n = 110) SOF-VEL x 12 weeks (n = 109) Treatment-Naïve 75 (68) 77 (71) Treatment-Experienced Peginterferon + Ribavirin Other 35 (32) 31 (89) 4 (11) 32 (29) 30 (94) 2 (6) Most Recent Treatment Response Nonresponder Relapse 16 (46) 3 (9) 8 (25) 20 (63) 4 (13) Source: Jacobson IM, et al. Gastroenterology. 2017;153:113-22.

Sofosbuvir-Velpatasvir-Voxilaprevir in GT 3 and Cirrhosis POLARIS-3: Results POLARIS-3: Overall SVR12 by Treatment Arm 106/110 105/109 Source: Jacobson IM, et al. Gastroenterology. 2017;153:113-22.

Sofosbuvir-Velpatasvir-Voxilaprevir in GT 3 and Cirrhosis POLARIS-3: Results POLARIS-3: Overall SVR12 by Treatment Arm 106/110 105/109 Source: Jacobson IM, et al. Gastroenterology. 2017;153:113-22.

Sofosbuvir-Velpatasvir-Voxilaprevir in GT 3 and Cirrhosis POLARIS-3: Results POLARIS-3: SVR12 by Treatment Experience 72/75 76/77 34/35 29/32 Source: Jacobson IM, et al. Gastroenterology. 2017;153:113-22.

Sofosbuvir-Velpatasvir-Voxilaprevir in GT 3 and Cirrhosis POLARIS-3: Results POLARIS-3: SVR12 by Baseline RAS 80/84 394/411 23/23 349/356 2/2 82/90 20/20 80 82 76 78 23 23 23 23 2 2 4 4 20 20 19 19 Y93H: 6 patients in SOF-VEL-VOX group and 4 in SOF-VEL group; all achieved SVR. No treatment-emergent RASs in SOF-VEL-VOX group. Both virologic failures in SOF-VEL group had Y93H. Source: Jacobson IM, et al. Gastroenterology. 2017;153:113-22.

Sofosbuvir-Velpatasvir-Voxilaprevir in GT 3 and Cirrhosis POLARIS-3: Adverse Events Adverse Event (AE), n (%) SOF/VEL/VOX 8 weeks (n=110) SOF/VEL 12 weeks (n=109) Discontinuation due to AE 1 (1) Serious AE 2 (2) 3 (3) Serious Related AE Deaths 1 (1) § Common AE Headache Fatigue Nausea Diarrhea 27 (25) 28 (25) 23 (21) 17 (15) 32 (29) 31 (28) 10 (9) 5 (5) Laboratory AEs (Grade 3-4) 14 (13) 9 (8) Source: Jacobson IM, et al. Gastroenterology. 2017;153:113-22.

Sofosbuvir-Velpatasvir-Voxilaprevir in GT 3 and Cirrhosis POLARIS-3: Conclusions Conclusions: “In phase 3 trials of patients with HCV infection, we did not establish that sofosbuvir-velpatasvir-voxilaprevir for 8 weeks was noninferior to sofosbuvir-velpatasvir for 12 weeks, but the 2 regimens had similar rates of SVR in patients with HCV genotype 3 and cirrhosis. Mild gastrointestinal adverse events were associated with treatment regimens that included voxilaprevir.” Source: Jacobson IM, et al. Gastroenterology. 2017;153:113-22.