Phase 3 Treatment Experienced

Slides:

Advertisements

Similar presentations

Hepatitis web study Hepatitis web study Sofosbuvir + Peginterferon + Ribavirin in Genotype 2 or 3 LONESTAR-2 Phase 2 Treatment Experienced Lawitz E, et.

Advertisements

Hepatitis web study Hepatitis web study Hepatitis web study Hepatitis web study Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir + RBV in GT1 SAPPHIRE-II.

Hepatitis web study Hepatitis web study Ledipasvir-Sofosbuvir +/- Ribavirin in HCV Genotype 1 ION-2 Phase 3 Treatment Experienced Source: Afdhal N, et.

Hepatitis web study Hepatitis web study Ledipasvir-Sofosbuvir for 8 or 12 weeks in HCV GT1 ION-3 Phase 3 Treatment Naïve Kowdley K, et al. N Engl J Med.

Hepatitis web study Hepatitis web study Ledipasvir-Sofosbuvir in GT1 or GT4 and HIV Coinfection ION-4 Phase 3 Treatment Naïve and Treatment Experienced.

Hepatitis web study Hepatitis web study Ledipasvir-Sofosbuvir +/- 3 rd DAA in HCV Genotype 1 NIAID SYNERGY Phase 2 Treatment Naïve (unfavorable baseline.

Hepatitis web study Hepatitis web study Ledipasvir-Sofosbuvir in Treatment-Experienced GT1 with Cirrhosis SIRIUS Phase 2 Treatment Experienced Bourliere.

Hepatitis web study Hepatitis web study Ledipasvir-Sofosbuvir + RBV in Sofosbuvir-Experienced HCV GT1 Retreatment of Sofosbuvir Failures Phase 2 Treatment.

Hepatitis web study Hepatitis web study 3D (Paritaprevir-Ritonavir-Ombitasvir + Dasabuvir) + RBV in GT1 SAPPHIRE-II Phase 3 Treatment Experienced Zeuzem.

Hepatitis web study Hepatitis web study Sofosbuvir + Ribavirin in HCV GT 4 Egyptian Ancestry Trial Phase 2 Ruane PJ, et al. J Hepatol. 2015;62:

Hepatitis web study Hepatitis web study Ledipasvir-Sofosbuvir in GT1 or GT4 and HIV Coinfection ION-4 Phase 3 Treatment Naïve and Treatment Experienced.

Hepatitis web study Hepatitis web study Daclatasvir + Sofosbuvir in Genotype 3 ALLY-3 Study Phase 3 Treatment-Naïve and Treatment-Experienced Nelson DR,

FUSION  Design  Objectives –SVR ≥ 20% compared with historical control of 25%, 97% power –Difference of SVR > 20% between the 2 groups, 82% power SOF.

Hepatitis web study Hepatitis web study Sofosbuvir + Peginterferon + Ribavirin in Genotype 2 or 3 LONESTAR-2 Phase 2 Treatment Experienced Lawitz E, et.

SOF/VEL 400/100 mg qd N = 120 W12 SOF + RBV > 18 years Chronic HCV infection Genotype 2 Naïve or pre-treatment with IFN-based regimen Compensated cirrhosis.

Hepatitis web study Hepatitis web study Elbasvir-Grazoprevir in Treatment-Naïve HCV Genotype 1, 4 or 6 C-EDGE Treatment Naïve (TN) Phase 3 Treatment Naïve.

Phase 3 Treatment Experienced

Design Randomisation* 1 : 1 Open-label W8 W12

Phase 3 Treatment-Naïve and Treatment-Experienced

Glecaprevir-Pibrentasvir in GT 1-6 with Renal Disease EXPEDITION-4

Sofosbuvir-Velpatasvir-Voxilaprevir in DAA-Naïve GT 1-6 POLARIS-2

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

Phase 3 Treatment-Naïve and Treatment-Experienced

Phase 3 Treatment-Naïve and Treatment-Experienced

Sofosbuvir-Velpatasvir (Epclusa)

Daclatasvir + Sofosbuvir in Genotype 3 ALLY-3 Study

> 18 years Chronic HCV infection Compensated cirrhosis **

Phase 3 Treatment-Naïve and Treatment-Experienced

Retreatment study: SOF/VEL + RBV in prior NS5A failure - Phase II

Design Randomisation* 1 : 1 Open-label W12

Phase 3 Treatment Experienced

Phase 3 Treatment-Naïve and Treatment-Experienced

Failure to achieve SVR on No HBV or HIV co-infection

Phase 3 Treatment-Naïve and Treatment-Experienced

QUARTZ II-III : OBV/PTV/r + SOF RBV in genotype 2 or 3

Sofosbuvir-Velpatasvir in HIV-HCV Coinfected Patients ASTRAL-5

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

Design Randomisation* 1 : 1 Double blind W12

SOF/VEL + GS-9857 in genotypes 1-6 Phase II

Phase 2 Treatment Naïve (unfavorable baseline treatment characteristics) Ledipasvir-Sofosbuvir +/- 3rd DAA in HCV Genotype 1 NIAID SYNERGY: Genotype.

Phase 2 Treatment Naïve Injection Drug Use

Elbasvir + Grazoprevir + Ribavirin in PI-experienced HCV GT1 C-SALVAGE

Phase 3 Treatment-Naïve and Treatment-Experienced

Phase 3 Treatment Naïve HIV Coinfection

Phase 3 Treatment-Naïve and Treatment-Experienced

Ombitasvir + Paritaprevir + Ritonavir +/- Ribavirin in HCV GT4 PEARL-I

Design W12 Randomisation * Open-label

GS-US Study: SOF/VEL + GS-9857 in genotype 1 - Phase II

Phase 3 Treatment-Naïve and Treatment-Experienced

Ledipasvir-Sofosbuvir +/- Ribavirin in HCV Genotype 1 ION-2

ION-3 Study: LDV/SOF + RBV for naïve genotype 1

GS-US Study: SOF/VEL + GS in genotype 2, 3, 4 or 6 - Phase II

LEPTON Study: SOF/VEL + GS-9857 genotype 1 or 3 Phase II

Phase 2 Treatment Naïve and Treatment Experienced

Ledipasvir-Sofosbuvir +/- Ribavirin for 8 or 12 weeks in HCV GT1 ION-3

Phase 2b Treatment Naïve and Treatment Experienced

MAGELLAN-3 Study: GLE/PIB + SOF + RBV in patients who failed GLE/PIB

LDV/SOF ± RBV in genotype 3 or 6 – Phase 2

Study : LDV/SOF in genotype 5

Daclatasvir + Asunaprevir in Genotype 1b HALLMARK-DUAL Study

No HBV or HIV co-infection

Phase 2 Treatment Naïve Elbasvir-Grazoprevir + Sofosbuvir in Treatment-Naïve HCV Genotype 1 or 3 C-SWIFT Poordad F, et al. EASL 2015; Abstract O006.

SOF/VEL in liver transplantation with genotype 1-4 infection

Phase 3 Treatment-Naïve and Treatment-Experienced

Phase 2 Treatment Experienced (with Sofosbuvir and Ribavirin)

Phase 3 Treatment-Naïve and Treatment-Experienced

SOF/VEL ± RBV in genotype 3 with compensated cirrhosis

Telaprevir in Treatment Experienced GT-1 PROVE3

Phase 3 Treatment-Naïve and Treatment-Experienced

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

Presentation transcript:

Phase 3 Treatment Experienced Sofosbuvir-Velpatasvir-Voxilaprevir in DAA-Experienced GT 1-6 POLARIS-4 Bourlière M, et al. N Engl J Med. 2017;376:2134-46.

Sofosbuvir-Velpatasvir-Voxilaprevir in DAA-Experienced GT 1-6 POLARIS-4: Study Features POLARIS-4 Trial Design: Open-label, randomized active-comparator, phase 3 trial to compare efficacy of a fixed-dose combination of sofosbuvir-velpatasvir- voxilaprevir versus sofosbuvir-velpatasvir for 12 weeks in DAA- experienced patients who had not received prior NS5A inhibitor. Setting: 102 sites in US, Canada, Europe, Australia & New Zealand Entry Criteria - Chronic HCV GT 1-6 (enrolled only GT 1-4) - HCV RNA ≥10,000 IU/mL at screening - DAA experienced (excluding prior NS5A use) - 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 Sofosbuvir-Velpatasvir-Voxilaprevir in DAA-Experienced GT 1-6 POLARIS-4: Study Study Design 12 24 Week GT 1-6 with prior DAA experience (no NS5A inhibitor) n = 333 Sofosbuvir-Velpatasvir- Voxilaprevir N=182 SVR12 Sofosbuvir-Velpatasvir N=151 SVR12 GT 1, 2, 3 patients randomized 1:1. Stratified by presence of cirrhosis. Genotypes 4 were assigned to active arm (and not randomized). No GT 5, 6 patients were enrolled. Drug Dosing Sofosbuvir-Velpatasvir-Voxilaprevir (400/100/100 mg): fixed dose combination; one pill once daily Sofosbuvir-Velpatasvir (400/100 mg): fixed dose combination; one pill once daily Source: Bourlière M, et al. N Engl J Med. 2017;376:2134-46.

Sofosbuvir-Velpatasvir-Voxilaprevir in DAA-Experienced GT 1-3 POLARIS-4: Baseline Characteristics SOF-VEL-VOX 12 weeks (n = 182) SOF-VEL (n = 151) Age, mean (range) 57 (25-85) 57 (24-80) Male, n (%) 143 (79) 114 (75) White, n (%) 160 (88) 131 (87) Genotype, % 1 1a 1b 2 3 4 78 (43) 54 (30) 24 (13) 31 (17) 54 (30) 19 (10) 66 (44) 44 (29) 22 (15) 33 (22) 52 (34) Body mass index, mean, kg/m2 (range) 29 (18-45) 29 (18-53) Mean HCV RNA, log10 IU/mL (range) 6.3 ± 0.6 6.3 ± 0.7 IL28B CC, n (%) 33 (18) 29 (19) Cirrhosis, n (%) 84 (46) 69 (46) Source: Bourlière M, et al. N Engl J Med. 2017;376:2134-46.

Sofosbuvir-Velpatasvir-Voxilaprevir in DAA-Experienced GT 1-3 POLARIS-4: Prior HCV Treatment NS5B NS5B + NS3 Other Other NS5B included mericitabine (n=7); other NS5B+NS3 included deleobuvir+faldaprevir (n=14), mercitabine+danoprevir (n=8), and SOF+telaprevir (n=6); one patient without prior DAA exposure is excluded. Source: Bourlière M, et al. N Engl J Med. 2017;376:2134-46.

Sofosbuvir-Velpatasvir-Voxilaprevir in DAA-Experienced GT 1-6 POLARIS-4: Results POLARIS-4: Overall SVR12 by Treatment Arm 177/182 136/151 P<0.001 for superiority compared with prespecified 85% performance goal for SOF-VEL-VOX Source: Bourlière M, et al. N Engl J Med. 2017;376:2134-46.

Sofosbuvir-Velpatasvir-Voxilaprevir in DAA-Experienced GT 1-6 POLARIS-4: Results POLARIS-4: Overall SVR12 by Treatment Arm 1 Relapse 1 Death 1 Lost to follow-up 1 Breakthrough 14 Relapses 177/182 136/151 P<0.001 for superiority compared with prespecified 85% performance goal for SOF-VEL-VOX Source: Bourlière M, et al. N Engl J Med. 2017;376:2134-46.

Sofosbuvir-Velpatasvir-Voxilaprevir in DAA-Experienced GT 1-6 POLARIS-4: Results POLARIS-4: SVR12 by Genotype 53/54 39/44 23/24 21/22 31/31 32/33 51/54 44/52 19/19 0/0 Source: Bourlière M, et al. N Engl J Med. 2017;376:2134-46.

Sofosbuvir-Velpatasvir-Voxilaprevir in DAA-Experienced GT 1-6 POLARIS-4: Results POLARIS-4: SVR12 by Cirrhosis Status 96/98 82/84 77/82 59/69 Source: Bourlière M, et al. N Engl J Med. 2017;376:2134-46.

Sofosbuvir-Velpatasvir-Voxilaprevir in DAA-Experienced GT 1-6 POLARIS-4: Results POLARIS-4: Overall SVR by Baseline RAS 84/89 67/75 83/83 63/70 39/39 29/32 40/40 32/34 4/4 2/4 N=22 patients had NS5B RASs – all went on to achieve SVR12. No treatment-emergent RASs noted in the viral relapser on SOF/VEL/VOX. In SOF/VEL group, 10/15 developed Y93H or Y93C. Source: Bourlière M, et al. N Engl J Med. 2017;376:2134-46.

Sofosbuvir-Velpatasvir-Voxilaprevir in DAA-Experienced GT 1-3 POLARIS-4: Adverse Events Adverse Event (AE), n (%) SOF/VEL/VOX 12 weeks (n=182) SOF/VEL (n=151) Discontinuation due to AE 1 (<1) Serious AE 4 (2) 4 (3) Deaths 1 (1) AE in ≥5% of patients Headache Fatigue Diarrhea Nausea 50 (27) 43 (24) 36 (20) 22 (12) 43 (28) 7 (5) 12 (8) Laboratory AEs (Grade 3-4) 11 (6) 10 (7) § One death in SOF/VEL/VOX group due to illicit drug overdose. Source: Bourlière M, et al. N Engl J Med. 2017;376:2134-46.

Sofosbuvir-Velpatasvir-Voxilaprevir in DAA-Experienced GT 1-3 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.