On 2015 Jan 29, Andrea Messori commented:

Clinical trials evaluating interferon-free treatments for previously untreated genotype 1 hepatitis C infection: state of the art in 2015

Fadda V, Messori A. Hta Unit, Regional Health Service, 50100 Firenze (Italy)

After the publication of the review by Doyle and co-workers (2013), numerous clinical trials have been conducted to evaluate interferon-free treatments for previously untreated hepatitis C infection. To retrieve these trials, we carried out a literature search based on the following criteria: a) enrolment of previously untreated patients with genotype 1 infection; b) administration combination treatments approved by EMA; c) end-point represented by sustained virologic response at the 12th week after completion of treatment (SVR12). Our search was exclusively based on the PubMed version of MEDLINE. The keywords for our initial search were intentionally generic (HCV OR “hepatitis C” combined with the filters of Clinical Trials and period from 2010 to 2014). Among the records extracted through our initial search (N=823), a subgroup of clinical trials (N=24) was selected that evaluated interferon-free treatments. After reading the full text of these 24 articles, we identified the studies that met the inclusion criteria set for our analysis. Our search on PubMed was run on 31 December 2014. The main characteristics of these trials are presented in Table 1.

Table 1. Rates of SVR12 achievement reported in 10 clinical trials (trials are identified based on first author, year of publication, and treatment; rates are reported in parenthesis).

1. Afdal, 2014: SOF/LED-12w (211/214)
2. Feld, 2014 (genotype 1 a): ARIODR-12w (307/322)
3. Feld, 2014 (genotype 1 b): ARIODR-12w (148/151)
4. Ferenci, 2014 (genotype 1 a): ARIOD-12w (185/205) and ARIODR-12w (97/100)
5. Ferenci, 2014 (genotype 1 b): ARIOD-12w (207/209) and ARIODR-12w (209/210)
6. Kowdley, 2014: ARIOD-12w (70/79) and ARIODR-12w (76/79)
7. Kowdley, 2014 (ION-3 trial): SOF/LED-12w (206/216) and SOF/LED-8w (202/215)
8. Lawitz, 2014 (LONESTAR trial): SOF/LED-12w (18/19) and SOF/LED-8w (19/20)
9. Poordad, 2014: ARIODR-12w (191/208)
10. Sulkowsky, 2014: SOF/DAC-12w (41/41)

Abbreviations: w, weeks: ARIODR-12w, ABT-450/ ritonavir/ombitasvir/dasabuvir/ribavirin for 12w; ARIOD-12w, ABT-450/ ritonavir/ombitasvir/dasabuvi for 12w; SOF/DAC-12w, sofosbuvir+daclatasvir for 12w; SOF/LED-8w, sofosbuvir+ledipasvir for 8w; SOF/LED-12w, sofosbuvir+ledipasvir for 12w . Note 1: Trials that reported separate results for patients with genotype 1a and 1b are presented seprately. Note 2: The following combinations treatments, that have been tested in naïve patients with genotype 1 infection, were not included in the above table: daclatasvir+asunaprevir for 24 w; beclabuvir+daclatasvir+asunaprevir for 12w; beclabuvir+daclatasvir+asunaprevir for 24w; sofosbuvir+simeprevir for 24w; sofosbuvir+simeprevir+ribavirin for 12w; sofosbuvir+simeprevir+ribavirin for 24w; sofosbuvir+ledipasvir+ribavirin for 8w; sofosbuvir+daclatasvir for 24w.

References

-Afdhal N, Zeuzem S, Kwo P, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014 May 15;370(20):1889-98.

-Doyle JS, Aspinall E, Liew D, Thompson AJ, Hellard ME. Current and emerging antiviral treatments for hepatitis C infection. Br J Clin Pharmacol. 2013 Apr;75(4):931-43. doi: 10.1111/j.1365-2125.2012.04419.x.

-Feld JJ, Kowdley KV, Coakley E et al. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014 Apr 24;370(17):1594-603.

-Ferenci P, Bernstein D, Lalezari J et al. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med. 2014 May 22;370(21):1983-92.

-Kowdley KV, Gordon SC, Reddy KR et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014 May 15;370(20):1879-88.

-Kowdley KV, Lawitz E, Poordad F et al. Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1. N Engl J Med. 2014 Jan 16;370(3):222-32.

-Lawitz E, Poordad FF, Pang PS et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014 Feb 8;383(9916):515-23.

-Poordad F, Hezode C, Trinh R et al. ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med. 2014 May 22;370(21):1973-82.

-Sulkowski MS, Gardiner DF, Rodriguez-Torres M et al. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med. 2014 Jan 16;370(3):211-21. doi: 10.1056/NEJMoa1306218. Erratum in: N Engl J Med. 2014 Apr 10;370(15):1469.

On 2015 Jan 29, Andrea Messori commented:

Clinical trials evaluating interferon-free treatments for previously untreated genotype 1 hepatitis C infection: state of the art in 2015

Fadda V, Messori A. Hta Unit, Regional Health Service, 50100 Firenze (Italy)

After the publication of the review by Doyle and co-workers (2013), numerous clinical trials have been conducted to evaluate interferon-free treatments for previously untreated hepatitis C infection. To retrieve these trials, we carried out a literature search based on the following criteria: a) enrolment of previously untreated patients with genotype 1 infection; b) administration combination treatments approved by EMA; c) end-point represented by sustained virologic response at the 12th week after completion of treatment (SVR12). Our search was exclusively based on the PubMed version of MEDLINE. The keywords for our initial search were intentionally generic (HCV OR “hepatitis C” combined with the filters of Clinical Trials and period from 2010 to 2014). Among the records extracted through our initial search (N=823), a subgroup of clinical trials (N=24) was selected that evaluated interferon-free treatments. After reading the full text of these 24 articles, we identified the studies that met the inclusion criteria set for our analysis. Our search on PubMed was run on 31 December 2014. The main characteristics of these trials are presented in Table 1.

Table 1. Rates of SVR12 achievement reported in 10 clinical trials (trials are identified based on first author, year of publication, and treatment; rates are reported in parenthesis).

1. Afdal, 2014: SOF/LED-12w (211/214)
2. Feld, 2014 (genotype 1 a): ARIODR-12w (307/322)
3. Feld, 2014 (genotype 1 b): ARIODR-12w (148/151)
4. Ferenci, 2014 (genotype 1 a): ARIOD-12w (185/205) and ARIODR-12w (97/100)
5. Ferenci, 2014 (genotype 1 b): ARIOD-12w (207/209) and ARIODR-12w (209/210)
6. Kowdley, 2014: ARIOD-12w (70/79) and ARIODR-12w (76/79)
7. Kowdley, 2014 (ION-3 trial): SOF/LED-12w (206/216) and SOF/LED-8w (202/215)
8. Lawitz, 2014 (LONESTAR trial): SOF/LED-12w (18/19) and SOF/LED-8w (19/20)
9. Poordad, 2014: ARIODR-12w (191/208)
10. Sulkowsky, 2014: SOF/DAC-12w (41/41)

Abbreviations: w, weeks: ARIODR-12w, ABT-450/ ritonavir/ombitasvir/dasabuvir/ribavirin for 12w; ARIOD-12w, ABT-450/ ritonavir/ombitasvir/dasabuvi for 12w; SOF/DAC-12w, sofosbuvir+daclatasvir for 12w; SOF/LED-8w, sofosbuvir+ledipasvir for 8w; SOF/LED-12w, sofosbuvir+ledipasvir for 12w . Note 1: Trials that reported separate results for patients with genotype 1a and 1b are presented seprately. Note 2: The following combinations treatments, that have been tested in naïve patients with genotype 1 infection, were not included in the above table: daclatasvir+asunaprevir for 24 w; beclabuvir+daclatasvir+asunaprevir for 12w; beclabuvir+daclatasvir+asunaprevir for 24w; sofosbuvir+simeprevir for 24w; sofosbuvir+simeprevir+ribavirin for 12w; sofosbuvir+simeprevir+ribavirin for 24w; sofosbuvir+ledipasvir+ribavirin for 8w; sofosbuvir+daclatasvir for 24w.

References

-Afdhal N, Zeuzem S, Kwo P, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014 May 15;370(20):1889-98.

-Doyle JS, Aspinall E, Liew D, Thompson AJ, Hellard ME. Current and emerging antiviral treatments for hepatitis C infection. Br J Clin Pharmacol. 2013 Apr;75(4):931-43. doi: 10.1111/j.1365-2125.2012.04419.x.

-Feld JJ, Kowdley KV, Coakley E et al. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014 Apr 24;370(17):1594-603.

-Ferenci P, Bernstein D, Lalezari J et al. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med. 2014 May 22;370(21):1983-92.

-Kowdley KV, Gordon SC, Reddy KR et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014 May 15;370(20):1879-88.

-Kowdley KV, Lawitz E, Poordad F et al. Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1. N Engl J Med. 2014 Jan 16;370(3):222-32.

-Lawitz E, Poordad FF, Pang PS et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014 Feb 8;383(9916):515-23.

-Poordad F, Hezode C, Trinh R et al. ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med. 2014 May 22;370(21):1973-82.

-Sulkowski MS, Gardiner DF, Rodriguez-Torres M et al. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med. 2014 Jan 16;370(3):211-21. doi: 10.1056/NEJMoa1306218. Erratum in: N Engl J Med. 2014 Apr 10;370(15):1469.