Provided by HIV – HCV - TB Pipeline Report
SVR in HCV Genotype 1, Treatment-Naive: Interferon-Free Regimens
Study/Drug | Population/Size | Treatment Arms | SVR | ||
Overall | HCV Subtype:1a vs. 1b | IL28B:CC vs. non-CC | |||
| AVIATOR ABT-450/r +/- ABT-267 +/- ABT-333 +/- RBV
Phase II AbbVie | Non-cirrhotic (N = 571) | 8-week, 4-drug | SVR-24: 88% | Overall: 91% vs. 98% | Overall: 95% vs. 89% |
| 12-week, 3-drug (no ABT-267) | 83% | ||||
| 12-week, 3-drug (no ABT-333) | 89% | ||||
| 12-week, 3-drug (no RBV) | 87% | ||||
| 12-week, 4-drug | 96% | ||||
| 24-week, 4-drug | 90% | ||||
| AI444-040 daclatasvir + sofosbuvir +/- RBV
Phase II Bristol-Myers Squibb/Gilead | Non-cirrhotic (N = 126) | 24-week, 2-drug (7-day sofosbuvir lead-in, no RBV) | SVR-24: 93% | No impact | |
| 24-week, 2-drug (no RBV) | 100% | ||||
| 24-week, 3-drug | 100% | ||||
| 12-week, 2-drug (no RBV) | SVR-12: 100% | ||||
| 12-week, 3-drug | SVR-12: 100% | ||||
| AI443-014 daclatasvir + asunaprevir + BMS-791325
Phase II Bristol-Myers Squibb | Non-cirrhotic (N = 32) | 12-week | SVR-24: 94% | No impact | |
| 24-week | SVR-24: 88% | ||||
| ELECTRON sofosbuvir + RBV
Phase II Gilead | Non-cirrhotic (N = 25) | 12-week | SVR-24: 84% | No impact | |
| ELECTRON FDC: | Non-cirrhotic (N = 25) | 12-week | SVR-12: 100% | No impact | |
| ELECTRON sofosbuvir + GS-9669 + RBV | Non-cirrhotic (N = 25) | 12-week | SVR-12: 92% | No impact | |
| LONESTAR sofosbuvir + ledipasvir +/- RBV
Phase II Gilead | Non-cirrhotic (N = 60) | 8-week, 2-drug (no RBV) | SVR-8: 95% | No impact | |
| 8-week, 3-drug | SVR-8: 100% |
| |||
| 12-week, 2-drug (no RBV) | SVR-4: 100% |
| |||
| SPARE sofosbuvir + weight-based (WB) or low-dose (LD) RBV
Phase II National Institutes of Health/Gilead | Non-cirrhotic (N = 10) | 24-week, WB RBV | SVR-24: 90% | No impact (most participants were HCV genotype 1a, non-CC IL28B, high baseline HCV RNA, and African American) | |
| All stages fibrosis (N = 50); advanced fibrosis/ compensated cirrhosis (13/50)
| 24-week, WB RBV | SVR-12: 68% | |||
| 24-week, LD RBV | SVR-12: 48% | ||||
| QUANTUM sofosbuvir + RBV
Phase II Gilead | Non-cirrhotic (N = 50); 6% cirrhotic | 12-week | SVR-12: 56% | No impact
| 100% vs. 42% |
| 24-week | 52% | 67% vs. 47% | |||
Sources:
Everson GT, Simms KD, Rodriguez-Torres M, et al. An interferon-free, ribavirin-free, 12-week regimen of daclatasvir (DCV), asunaprevir (ASV) and BMS-791325 yielded SVR-4 of 94% in treatment-naive patients with genotype (GT) 1 chronic hepatitis C virus (HCV) infection (Abstract LB-3). Paper presented at: 63rd Annual Meeting of the American Association for the Study of Liver Diseases; 2012 November 9–13; Boston, Massachusetts.
Everson GT, Simms KD, Rodriguez-Torres M, et al. Interim analysis of an interferon (IFN)- and ribavirin-(RBV) free regimen of daclatasvir (DCV), asunaprevir (ASV) and BMS-791325 in treatment-naive, hepatitis C virus genotype 1-infected patients (Abstract 1423). Paper presented at: 48th Annual Meeting of the European Association for the Study of the Liver; 2013 April 24–28; Amsterdam, the Netherlands.
Gane EJ, Stedman CA, Hyland RH, et al. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med. 2013 Jan 3;368(1):34–44. doi: 10.1056/NEJMoa1208953.
Gane EJ, Stedman CA, Hyland RH, Ding X, Pang PS, Symmonds WT. ELECTRON: 100% SVR rates for once-daily sofosbuvir plus ledipasvir plus ribavirin given for 12 weeks in treatment-naive and previously treated patients with HCV genotype 1 (Abstract 41 LB). Paper presented at: 20th Conference on Retroviruses and Opportunistic Infections (CROI); 2013 March 3–6; Atlanta, Georgia. Abstract available from: http://www.retroconference.org/2013b/Abstracts/47869.htm. (Accessed on 2013 April 15)
Gane EJ, Stedman CA, Hyland RH, et al. All-oral sofosbuvir-based 12-week regimens for the treatment of chronic HCV GT1 infection: the ELECTRON study (Abstract 14). Paper presented at: 48th Annual Meeting of the European Association for the Study of the Liver; 2013 April 24–28; Amsterdam, the Netherlands.
Gilead Sciences (Press Release). Gilead reports interim data from phase 2 LONESTAR study. 2013 May 2. Available from: http://www.gilead.com/news/press-releases/2013/5/gilead-reports-interim-data-from-phase-2-lonestar-study. (Accessed on May 2, 2013)
King M, Xie W, Larsen L, Cohen D, Podsadecki, T, Bernstein B. Risk of virologic relapse in hepatitis C virus GT1-infected subjects after 8, 12, and 24 weeks of ABT-450/r+ABT-267+ABT-333+ribavirin: identifying optimal treatment duration (Abstract 39). Paper presented at: 20th Conference on Retroviruses and Opportunistic Infections; 2013 March 3–6; Atlanta, Georgia. Abstract available from: http://www.retroconference.org/2013b/Abstracts/46833.htm. (Accessed on April 15, 2013)
Kowdley KV, Lawitz E, Poordad F, et al. A 12-week interferon-free treatment regimen with ABT-450/r, ABT-267, ABT-333 and ribavirin achieves SVR-12 rates of 99% in treatment-naive patients and 93% in prior null responders with HCV genotype 1 infection (Abstract LB-1). Paper presented at: 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD); 2012 November 9–13; Boston, Massachusetts.
Kowdley KV, Lawitz E, Poordad F, et al. Safety and efficacy of interferon-free regimens of ABT-450/r, ABT-267, ABT-333 +/- ribavirin in patients with chronic HCV genotype 1: results from the AVAITOR study (Abstract 3). Paper presented at: 48th Annual Meeting of the European Association for the Study of the Liver; 2013 April 24–28; Amsterdam, the Netherlands.
Lalazeri JP, Nelson DR, Hyland RH, et al. Once-daily sofosbuvir plus ribavirin given for 12 or 24 weeks in treatment-naïve patients with HCV: the QUANTUM study (Abstract 845). Paper presented at: 48th Annual Meeting of the European Association for the Study of the Liver; 2013 April 24–28; Amsterdam, the Netherlands.
Osinusi A, Meissner EG, Bon D, et al.; NIAID SPARE Study Team. High efficacy of sofosbuvir in combination with weight-based ribavirin for 24 weeks in difficult to treat HCV infected genotype-1 patients (Abstract 157-LB). Paper presented at: 20th Conference on Retroviruses and Opportunistic Infections; 2013 March 3–6; Atlanta, Georgia. Available from: http://www.retroconference.org/AbstractSearch/default2.aspx?conf=22. (Accessed on 2013 May 2)
Sulkowski MS, Gardnier DF, Rodriguez-Torres M, et al; for the AI444040 Study Group. High rate of sustained virologic response with the all-oral combination of daclatasvir (NS5A inhibitor) plus sofosbuvir (nucleotide NS5B inhibitor), with or without ribavirin, in treatment-naive patients chronically infected with HCV GT 1, 2, or 3 (Abstract LB-2). Paper presented at: 63rd Annual Meeting of the American Association for the Study of Liver Diseases; 2012 November 9–13; Boston, Massachusetts.
SVR in HCV Genotype 1, Treatment-Naive: Interferon-Sparing Regimens
Study/Drug | Population/Size | Treatment Arms | SVR | ||
Overall | HCV Subtype:1a vs. 1b | IL28B:CC vs. non-CC | |||
| ATOMIC sofosbuvir + PEG-IFN/RBV
Phase II Gilead | Non-cirrhotic (N = 316) | 12-week, 3-drug | SVR-24: 89% | Not reported; 10/11 relapsers had non-CC genotype | |
| 24-week | SVR-24: 89% | ||||
| 12-week, 3-drug + 12-week SOF or SOF/RBV | SVR-24: 87% | ||||
| NEUTRINO sofosbuvir + PEG-IFN/RBV
Phase III Gilead | N = 291 17% cirrhotic | 12-week | SVR-12: 100% Cirrhotic: 80% Non-cirrhotic: 92% | 92% vs. 82% | 98% vs. 87% |
Sources:
Kowdley KV, Lawitz E, Crespo I, et al. Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial. Lancet. 2013 Mar 14. Available from: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60247-0/fulltext. (Accessed on 2013 April 20)
Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013 Apr 23. Available from: http://www.nejm.org/doi/full/10.1056/NEJMoa1214853. (Accessed on 2013 May 2)
SVR in HCV Genotype 1, Treatment-Experienced: Interferon-Free Regimens
Study/Drug | Population/Size | Treatment Arms | SVR | |||
Overall | HCV Subtype:1a vs. 1b | IL28B:CC vs. non-CC | ||||
| AVIATOR ABT-450/r + ABT-267 +/- ABT-333 + RBV
Phase II AbbVie | Non-cirrhotic, null responders (N = 133) | 12-week, 3-drug (no ABT-333) | SVR-24: 89% | 93% vs. 97% | 94% vs. 100%
| |
| 12-week, 4-drug | 93% | |||||
| 24-week, 4-drug | 95% | |||||
| AI444-040 daclatasvir + sofosbuvir +/- RBV
Phase II Bristol-Myers Squibb/Gilead | Non-cirrhotic, prior boceprevir or telaprevir use (N = 41) | 24-week, 2-drug (no RBV) | SVR-12: 100% | No impact | ||
| 24-week, 3-drug | 100% | |||||
| 24-week | SVR-24: 88% | |||||
| COSMOS (Interim data) simeprevir + sofosbuvir +/- RBV
Phase II Janssen/Gilead | Non-cirrhotic, null responders (N = 80) 100% non-CC genotype | 12-week, 2-drug | SVR-8: 92.9% | No impact | N/A | |
| 12-week, 3-drug | 96.3% | |||||
| 24-week, 2-drug | 100% (5/5) | |||||
| 24-week, 3-drug | 66.7% (4/6) | |||||
| ELECTRON sofosbuvir + RBV
Phase II Gilead | Non-cirrhotic, null responders (N = 10) | 12-week | SVR-24: 11% | No impact | ||
| ELECTRON FDC: | Non-cirrhotic, null responders (N = 10) | 12-week | SVR-4: 100% | No impact | ||
| LONESTAR (Interim data) sofosbuvir + ledipasvir +/-RBV
Phase II Gilead | Non-cirrhotic, prior boceprevir or telaprevir use (N = 40) | 12-week, 2-drug (no RBV) | SVR-4: 95% | No impact
| ||
| 12-week, 3-drug | SVR-4: 95% | |||||
| QUANTUM (Retreatment) sofosbuvir + RBV
Phase II Gilead | N = 105 10% cirrhotic in control or discontinued arms | 24-week, 2-drug retreatment | SVR-12: 66% | 71% vs. 48% | 84% vs. 63% | |
Sources:
Gane EJ, Stedman CA, Hyland RH, et al. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med. 2013 Jan 3;368(1):34-44. doi:10.1056/NEJMoa1208953.
Gane EJ, Stedman CA, Hyland RH, Ding X, Pang PS, Symmonds WT. ELECTRON: 100% SVR rates for once-daily sofosbuvir plus ledipasvir plus ribavirin given for 12 weeks in treatment-naive and previously treated patients with HCV genotype 1 (Abstract 41 LB). Paper presented at: 20th Conference on Retroviruses and Opportunistic Infections; 2013 March 3–6; Atlanta, Georgia. Available from: http://www.retroconference.org/2013b/Abstracts/47869.htm. (Accessed on 2013 April 21)
Gane EJ, Stedman CA, Hyland RH, et al. ELECTRON: all-oral sofosbuvir-based 12-week regimens for the treatment of chronic HCV GT1 infection (Abstract 14). Paper presented at: 48th Annual Meeting of the European Association for the Study of the Liver; 2013 April 24–28; Amsterdam, the Netherlands.
Gilead Sciences (Press Release). Gilead reports interim data from phase 2 LONESTAR study. 2013 May 2. Available from: http://www.gilead.com/news/press-releases/2013/5/gilead-reports-interim-data-from-phase-2-lonestar-study. (Accessed on 2013 May 2)
Kowdley KV, Lawitz E, Poordad F, et al. Safety and efficacy of interferon-free regimens of ABT-450/r, ABT-267, ABT-333 +/- ribavirin in patients with chronic HCV genotype 1: results from the AVIATOR study (Abstract 3). Paper presented at: 48th Annual Meeting of the European Association for the Study of the Liver; 2013 April 24–28; Amsterdam, the Netherlands.
Lawitz E, Ghalib R, Rodriguez-Torres M, et al. Suppression of viral load through 4 weeks post-treatment: results of a once-daily regimen of simeprevir + sofosbuvir with or without ribavirin in hepatitis C virus GT1 null repsonders (Abstract 155 LB). Paper presented at: 20th Conference on Retroviruses and Opportunistic Infections; 2013 March 3–6; Atlanta, Georgia. Available from: http://www.retroconference.org/2013b/Abstracts/47930.htm. (Accessed on 2013 April 18)
Lalazeri JP, Nelson DR, Hyland RH, et al. Once-daily sofosbuvir plus ribavirin given for 12 or 24 weeks in treatment-naïve patients with HCV: the QUANTUM study (Abstract 845). Paper presented at: 48th Annual Meeting of the European Association for the Study of the Liver; 2013 April 24–28; Amsterdam, the Netherlands.
Sulkowski MS, Gardiner DF, Rodriguez-Torres M, et al. Sustained virologic response with daclatasvir plus sofosbuvir ± ribavirin (RBV) in chronic HCV genotype (GT) 1-infected patients who previously failed telaprevir (TVR) or boceprevir (BOC) (Abstract 1417). Paper presented at: 48th Annual Meeting of the European Association for the Study of the Liver; 2013 April 24–28; Amsterdam, the Netherlands.
SVR in HCV Genotypes 2 and 3
Study/Drugs | Population/Size | Genotype | Treatment Arms | SVR |
| AI444-040 daclatasvir + sofosbuvir +/−RBV
Phase II Bristol-Myers Squibb/Gilead | Treatment-naive, non-cirrhotic (N = 44) | Genotypes 2 and 3
| 24-week, 2-drug (7-day sofosbuvir lead-in, no RBV) | SVR-24: 88% |
| 24-week, 2-drug (no RBV) | SVR-24: 100% | |||
| 24-week, 3-drug | SVR-24: 93% | |||
| COMMAND GT 2/3 daclatasvir + PEG-IFN/RBV vs. placebo + PEG-IFN/RBV
Phase II Bristol-Myers Squibb | Treatment-naive, 20% cirrhotic (G3 only) (N = 151) | Genotype 2 | 12-week (N = 24) | SVR-24: 88% |
| 16-week (N = 23) | SVR-24: 83% | |||
| placebo (N = 24) | SVR-24: 63% | |||
| Genotype 3 | 12-week (N = 26) | SVR-24: 69% | ||
| 16-week (N = 27) | SVR-24: 70% | |||
| placebo (N = 27) | SVR-24: 59% | |||
| ELECTRON sofosbuvir + RBV + 0, 4, 8, or 12 weeks of PEG-IFN vs. sofosbuvir monotherapy
Phase II Gilead | Treatment-naive, non-cirrhotic (N = 60) | Genotypes 2 and 3
| 8-week, 3-drug (N = 10) | SVR-24: 100% |
| 12-week, with 4-week PEG-IFN (N = 9) | SVR-24: 100% | |||
| 12-week, with 8-week PEG-IFN (N = 10) | SVR-24: 100% | |||
| 12-week, 3-drug (N = 11) | SVR-24: 100% | |||
| 12-week, no PEG-IFN (N = 10) | SVR-24: 100% | |||
| 12-week, sofosbuvir only (N = 10) | SVR-24: 60% | |||
| FISSION sofosbuvir + RBV vs. PEG-IFN/RBV
Phase III Gilead | Treatment-naive, 20% cirrhotic (N = 499) | Genotype 2 | 12-week sofosbuvir + RBV | SVR-12: 97% Cirrhotic: 91% Non-cirrhotic: 98% |
| 24-week PEG-IFN/RBV | SVR-12: 78% Cirrhotic: 62% Non-cirrhotic: 82% | |||
| Genotype 3 | 12-week sofosbuvir + RBV | SVR-12: 56% Cirrhotic: 34% Non-cirrhotic: 61% | ||
| 24-week PEG-IFN/RBV | SVR-12: 63% Cirrhotic: 30% Non-cirrhotic: 71% | |||
| FUSION sofosbuvir + RBV
Phase III Gilead
| Treatment-experienced, 34% cirrhotic (N = 201) | Genotype 2 | 12-week | SVR-12: 86% Cirrhotic: 60% Non-cirrhotic: 96% |
| 16-week | SVR-12: 94% Cirrhotic: 78% Non-cirrhotic: 100% | |||
| Genotype 3 | 12-week | SVR-12: 30% Cirrhotic: 19% Non-cirrhotic: 37% | ||
| 16-week | SVR-12: 62% Cirrhotic: 61% Non-cirrhotic: 63% | |||
| POSITRON sofosbuvir + RBV
Phase III Gilead | Treatment naive, interferon-ineligible, -intolerant, and -unwilling, 15% cirrhotic (N = 207) | Genotype 2 | 12-week | SVR-12: 93% Cirrhotic: 94% Non-cirrhotic: 92% |
| Genotype 3
| 12-week | SVR-12: 61% Cirrhotic: 21% Non-cirrhotic: 68% | ||
| PROTON sofosbuvir + PEG-IFN/RBV
Phase II Gilead | Treatment-naive, non-cirrhotic (N = 25) | Genotypes 2 and 3 | 12-week | SVR-12: 92% |
Sources:
Dore GJ, Lawitz E, Hézode C, et al. Daclatasvir combined with peginterferon alfa-2a and ribavirin for 12 or 16 weeks in patients with hepatitis C virus genotype 2 or 3 infection: COMMAND GT 2/3 study (Abstract 1418). Paper presented at: 48th Annual Meeting of the European Association for the Study of the Liver; 2013 April 24–28; Amsterdam, the Netherlands.
Gane EJ, Stedman CA, Hyland RH, et al. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med. 2013 Jan 3;368(1):34–44. doi: 10.1056/NEJMoa1208953.
Jacobson IM, Gordon SC, Kowdley KV, et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med. 2013 Apr 23. Available from: http://www.nejm.org/doi/full/10.1056/NEJMoa1214854. (Accessed 2013 May 3)
Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013 Apr 23. Available from: http://www.nejm.org/doi/full/10.1056/NEJMoa1214853. (Accessed 2013 May 3)
Lawitz E, Lalezari JP, Hassanein T, et al. Sofosbuvir in combination with peginterferon alfa-2a and ribavirin for non-cirrhotic, treatment-naive patients with genotypes 1, 2, and 3 hepatitis C infection: a randomised, double-blind, phase 2 trial. Lancet Infect Dis. 2013 May;13(5):401–8. doi: 10.1016/S1473-3099(13)70033-1
SVR in HCV Genotype 4, 5, and 6, Treatment-Naive: Interferon-Sparing Regimens
Study/Drug | Population | HCV Genotype/Size | Duration | SVR |
| ATOMIC sofosbuvir + PEG-IFN/RBV
Phase II Gilead | Non-cirrhotic | Genotype 4 (N = 11) | 24-week | SVR-24: 82% |
| Genotype 5 (N = 6) | SVR-24: 82% | |||
| NEUTRINO sofosbuvir + PEG-IFN/RBV
Phase III Gilead | Liver histology not available | Genotype 4 (N = 28) | 12-week
| SVR-12: 96%
|
| Genotype 5 (N = 1) | SVR-12: 100% | |||
| Genotype 6 (N = 6) | SVR-12: 100% |
Sources:
Kowdley KV, Lawitz E, Crespo I, et al. Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial. Lancet. 2013 Mar 14. Available from: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60247-0/fulltext. (Accessed on 2013 April 20)
Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013 Apr 23. Available from: http://www.nejm.org/doi/full/10.1056/NEJMoa1214853. (Accessed on 2013 May 2)
