July 7, 2013

2013 SVR Updates

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:
sofosbuvir/ledipasvir + RBV

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:
sofosbuvir/ledipasvir + RBV

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)

Source

 

0 comments :

Post a Comment