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Presentation transcript:

Phase 3 Treatment Experienced Sofosbuvir-Velpatasvir-Voxilaprevir in NS5A-Experienced GT 1-6 POLARIS-1 Bourlière M, et al. N Engl J Med. 2017;376:2134-46.

Sofosbuvir-Velpatasvir-Voxilaprevir in NS5A-Experienced GT 1-6 POLARIS-1: Study Features POLARIS-1 Trial Design: Randomized, placebo-controlled, phase 3 trial to evaluate the efficacy of a fixed-dose combination of sofosbuvir-velpatasvir-voxilaprevir for 12 weeks in NS5A-inhibitor-experienced patients with GT 1-6 chronic HCV infection Setting: - 108 sites in United States, Canada, New Zealand, Australia, France, Germany, and United Kingdom Entry Criteria - Age >18 years - Chronic HCV (any genotype) - HCV RNA ≥10,000 IU/mL at screening - Prior treatment failure with DAA that contained NS5A inhibitor - Patients with compensated cirrhosis allowed Primary End-Point: SVR12 Source: Bourlière M, et al. N Engl J Med. 2017;376:2134-46.

Sofosbuvir-Velpatasvir- Sofosbuvir-Velpatasvir-Voxilaprevir in NS5A-Experienced GT 1-6 POLARIS-1: Study Design 12 24 Week GT 1-6 with NS5A inhibitor experience* n = 415 Sofosbuvir-Velpatasvir- Voxilaprevir N=263 SVR12 Placebo N=152 SVR12 GT 1 patients randomized 2:1 ratio (active:placebo). Stratified by presence of cirrhosis (target ≥30%). Genotypes 2-6 were assigned to active arm (and not randomized). Placebo recipients were eligible for deferred treatment with sofosbuvir-velpatasvir-voxilaprevir Drug Dosing Sofosbuvir-Velpatasvir-Voxilaprevir (400/100/100 mg): fixed dose combination; one pill once daily Placebo: one pill once daily Source: Bourlière M, et al. N Engl J Med. 2017;376:2134-46.

Sofosbuvir-Velpatasvir-Voxilaprevir in NS5A-Experienced GT 1-6 POLARIS-1: Baseline Characteristics SOF-VEL-VOX (n = 263) Placebo ( n =152) Age, mean (range) 58 (27-84) 59 (29-80) Male, n (%) 200 (76) 121 (80) White, n (%) 211 (80) 124 (82) HCV genotype—no. (%) 1 1a 1b 1 (other) 2 3 4 5 6 150 (57) 101 (38) 45 (17) 4 (2) 5 (2) 78 (30) 22 (8) 1 (<1) 6 (2) 150 (99) 117 (77) 31 (20) 2 (1) Mean HCV RNA, log10 IU/mL (range) 6.3 ± 0.7 6.3 ± 0.6 IL28B CC, n (%) 47 (18) 27 (18) Cirrhosis, n (%) 121 (46) 51 (34) Source: Bourlière M, et al. N Engl J Med. 2017;376:2134-46.

Sofosbuvir-Velpatasvir-Voxilaprevir in NS5A-Experienced GT 1-6 POLARIS-1: Prior NS5A Treatment 133/263 70/263 30/263 33/263 Source: Bourlière M, et al. N Engl J Med. 2017;376:2134-46.

Sofosbuvir-Velpatasvir-Voxilaprevir in NS5A-Experienced GT 1-6 POLARIS-1: Results POLARIS-1: SVR12 Results by Genotype 97/101 45/45 5/5 74/78 20/22 1/1 6/6 Source: Bourlière M, et al. N Engl J Med. 2017;376:2134-46.

Sofosbuvir-Velpatasvir-Voxilaprevir in NS5A-Experienced GT 1-6 POLARIS-1: Results POLARIS-1: SVR 12 by Cirrhosis Status 253/263 140/142 113/121 Source: Bourlière M, et al. N Engl J Med. 2017;376:2134-46.

Sofosbuvir-Velpatasvir-Voxilaprevir in NS5A-Experienced GT 1-6 POLARIS-1: Results POLARIS-1: SVR 12 by Cirrhosis Status 6 Relapses 1 On-treatment failure 2 Withdrew consent 1 Lost to follow-up 6 Relapses 1 On-treatment failure 1 Withdrew consent 1 Withdrew consent 1 Lost to follow-up 253/263 140/142 113/121 Source: Bourlière M, et al. N Engl J Med. 2017;376:2134-46.

Sofosbuvir-Velpatasvir-Voxilaprevir in NS5A-Experienced GT 1-6 POLARIS-1: Results POLARIS-1: SVR12 by Baseline Resistance-Associated Substitutions (RAS) 42/43 199/205 2/2 9/9 120/124 70/72 83% of patients had baseline resistance-associated substitutions (RASs); 79% had NS5A RASs. None who relapsed had treatment-emergent RASs. Source: Bourlière M, et al. N Engl J Med. 2017;376:2134-46.

Sofosbuvir-Velpatasvir-Voxilaprevir in NS5A-Experienced GT 1-6 POLARIS-1: Adverse Events Adverse Event (AE) SOF-VEL-VOX (n = 263) Placebo (n = 152) Discontinuation due to AE—no. (%) 1 (<1) § 3 (2) Serious AEs—no. (%) 5 (2) 7 (5) Deaths—no. Any AE in ≥5% of patients—no. (%) Headache Fatigue Diarrhea Nausea 66 (25) 56 (21) 47 (18) 37 (14) 26 (17) 30 (20) 19 (12) 12 (8) Laboratory AEs Grade 3 or Above—no. (%) 18 (6.9%) 22 (14.5%) § One patient in active arm discontinued due to angioedema attributed to ramipril. Source: Bourlière M, et al. N Engl J Med. 2017;376:2134-46.

Sofosbuvir-Velpatasvir-Voxilaprevir in DAA-Experienced GT 1-6 POLARIS-1 and POLARIS-4: Conclusions Conclusions: “Sofosbuvir-velpatasvir-voxilaprevir taken for 12 weeks provided high rates of sustained virologic response among patients across HCV genotypes in whom treatment with a DAA regimen had previously failed.” Source: Bourlière M, et al. N Engl J Med. 2017;376:2134-46.