Streamlining HCV Treatment
By Tracy Swan
Treatment for hepatitis C virus (HCV) is becoming simpler, shorter, and more effective. All-oral combinations of direct-acting antivirals (DAAs) have pushed cure rates in HCV genotype 1 to over 90 percent. Still, we are far from having a single-tablet regimen (STR) suitable for everyone. Peginterferon-free treatment is less effective against HCV genotype 3, and very little is known about treating genotypes 4, 5, and 6 with DAAs.
More information is needed on the safety, efficacy, and tolerability of DAAs in those likely to be prioritized for HCV treatment. Despite dozens of ongoing trials, data on DAA-based regimens in people with cirrhosis—especially those who are treatment-experienced—are limited. As of May 2013, there was only one peginterferon-free trial available to people coinfected with HIV and HCV.
The next direct-acting antivirals likely to be approved are simeprevir, a protease inhibitor, and sofosbuvir, a nucleotide polymerase inhibitor. These drugs have been studied with peginterferon and ribavirin, and in various peginterferon-free regimens, with and without ribavirin.
Although simeprevir and sofosbuvir are likely to be used in different ways than those for which they were developed, both drugs were highly effective in combination with peginterferon and ribavirin, either in fixed-duration or response-guided regimens. Response-guided treatment with 12 weeks of simeprevir plus peginterferon and ribavirin (24 or 48 weeks) cured 80 percent of participants in QUEST-1 and QUEST-2, trials in treatment-naive people with HCV genotype 1; most were treated for only 24 weeks.
HCV Genotype 1, Treatment-Naive
Peginterferon-free and peginterferon-sparing combinations have been highly effective against HCV genotype 1, regardless of viral subtype, IL28B genotype, and hepatitis C viral load. With these regimens, treatment duration is fixed (rather than response-guided); most are taken for 12 weeks. Extending treatment to 24 weeks does not appear to increase cure rates. After 12 weeks of treatment, 56 percent to 100 percent of participants in clinical trials were cured; most regimens yielded cure rates of at least 80 percent. (See table 1, SVR in HCV Genotype 1, Treatment-Naive: Interferon-Free Regimens.)
Although sofosbuvir has become a backbone for many peginterferon-free regimens, the initial indication in genotype 1 (and genotype 4) is for 12 weeks in combination with peginterferon and ribavirin. With this regimen, cure rates reached 89 percent (and 80 percent in people with cirrhosis). (See table 2, SVR in HCV Genotype 1, Treatment-Naive: Interferon-Sparing Regimens.)
Table 1. 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, MA.
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; 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 2013 May 2)
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 2013 April 15)
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, MA.
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, GA. Available from: http://www.retroconference.org/AbstractSearch/default2.aspx?conf=22. (Accessed 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, MA.
Table 2. 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 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)
HCV Genotype 1, Treatment-Experienced
Trials of “quad”—two DAAs plus peginterferon and ribavirin, or response-guided therapy—are gradually being supplanted by peginterferon-free regimens in treatment-experienced people. Proof-of-concept can be quickly demonstrated in prior null responders, since what cures a null responder—especially one with cirrhosis—it is likely to be even more effective for treatment-naive people).
Re-treatment with a 12- or 24-week regimen of two, three, four, or five drugs is being explored in treatment-experienced people with HCV genotype 1. Most trials have been conducted in people who were unsuccessfully treated with peginterferon and ribavirin, but two regimens (sofosbuvir and an NS5a inhibitor [either daclatasvir or ledipasvir], with or without ribavirin) have been studied in people who were unsuccessfully treated with peginterferon, ribavirin, and an HCV protease inhibitor.
Cure rates have ranged from a dismal 11 percent to 100 percent; most regimens have cured around 90 percent of treatment-experienced trial participants (the majority with poor prognostic factors: IL28B CT or TT genotype, HCV genotype 1a, and high hepatitis C viral loads). (See table 3, SVR in HCV Genotype 1, Treatment-Experienced: Interferon-Free Regimens.)
Table 3. 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% | |||||
| 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% (13/14) | No impact | N/A | |
| 12-week, 3-drug | 96.3% (26/27) | |||||
| 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, GA. 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, GA. Available from: http://www.retroconference.org/2013b/Abstracts/47930.htm. (Accessed 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.
HCV Genotypes 2 and 3
Until the DAA era, genotypes 2 and 3 were considered easily cured. Indeed, it is easy to cure genotype 2, regardless of cirrhosis or prior treatment failure. But HCV genotype 3 is proving to be a challenge. Only one peginterferon-free regimen—sofosbuvir plus daclatasvir, with or without ribavirin—has yielded cure rates above 65 percent, after 24 weeks of treatment.
Adding peginterferon to a 12-week course of sofosbuvir and ribavirin seems to boost cure rates. Adding peginterferon to sofosbuvir and ribavirin for 4 or 8 weeks pushed cure rates to 100 percent in HCV genotype 3. (See table 4, SVR in HCV Genotypes 2 and 3.)
Table 4. 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.
HCV Genotypes 4, 5 and 6
Ongoing trials are exploring different regimens in HCV genotype 4. Final data are available in HCV genotype 4 after 12 or 24 weeks of treatment with sofosbuvir plus peginterferon and ribavirin. Only 39 people with HCV genotype 4 were treated; cure rates were 82 percent after 24 weeks and 96 percent after 12 weeks.
To date, sofosbuvir, peginterferon and ribavirin is the only regimen to have been studied in HCV genotypes 5 and 6—albeit in only 13 people, one with genotype 5. (See table 5, SVR in HCV Genotypes 4, 5, and 6, Treatment-Naive: Interferon-Sparing Regimens.)
Table 5. SVR in HCV Genotypes 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 6 (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)