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Information |
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Generic Name:
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sofosbuvir + ledipasvir
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Trade Name: |
Harvoni |
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Synonym: |
GS-7977, GS-5855 |
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Entry Type: |
New formulation |
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Developmental Status |
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UK: |
Recommended for approval (Positive opinion) |
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EU: |
Recommended for approval (Positive opinion) |
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US: |
Approved (Licensed) |
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UK launch Plans: |
Available only to registered users |
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Actual UK launch date: |
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Comments |
Oct 14: Approved in the US for HCV genotype 1 infection. Approval is based on three PIII studies which showed that Harvoni achieved cure rates (SVR 12) of 94%-99% [17].
13/10/2014 11:15:54 |
Sep 14: EU positive opinion for treatment of chronic hepatitis C infection in adults [16].
29/09/2014 14:24:50 |
Apr 14: Granted priority review in the US. A decision on approval is expected by 10 Oct [14]
07/04/2014 19:33:19 |
Feb 14: EU CHMP issues an opinion on the use of a fixed-dose combination of ledipasvir and sofosbuvir in the treatment of chronic HCV infection in a compassionate use programme. The assessment report and conditions of use of the combination of ledipasvir and sofosbuvir with or without ribavirin in this setting will be published shortly on the EMA´s website [13].
24/02/2014 11:44:21 |
Feb 14: Filed in the EU for treatment of chronic hepatitis C genotype 1 infection in adults [12].
13/02/2014 10:57:02 |
Feb 14: Filed in the US as a once-daily fixed-dose combination of ledipasvir 90mg and sofosbuvir 400mg for the treatment of chronic hepatitis C genotype 1 infection in adults [11]
11/02/2014 15:45:52 |
Dec 13: Company plans to file in US Q1 2014,where it has been award Breakthrough designation [10]
19/12/2013 21:51:52 |
Oct 12: PIII study starts in US, EU & UK [2].
08/10/2012 17:57:03 |
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Trial or other data |
Apr 14: NHS England commissioned. Patients eligible for treatment are those with significant risk of death or irreversible damage within the next 12 months, irrespective of genotype [15]
22/04/2014 09:17:03 |
Apr 14: Results from three PIII studies published early on-line in the NEJM: ION-1 (http://www.nejm.org/doi/full/10.1056/NEJMoa1402454), ION-2 (http://www.nejm.org/doi/full/10.1056/NEJMoa1316366) and ION-3 (http://www.nejm.org/doi/full/10.1056/NEJMoa1402355)
14/04/2014 08:37:45 |
Feb 14: Results of the PII LONESTAR study (n=100) published in the Lancet Feb 8 2014: 383: 515-23. The study found that the fixed dose-combination of sofosbuvir-ledipasvir alone or with ribavirin has the potential to cure most patients with genotype-1 HCV irrespective of treatment history or presence of compensated cirrhosis.
11/02/2014 15:10:32 |
Dec 13: Topline results announced from three PIII clinical trials (ION-1, ION-2 and ION-3) of the once-daily fixed-dose combination of sofosbuvir 400mg ledipasvir 90mg, with and without ribavirin, for the treatment of genotype 1 chronic HCV infection. 1,952 patients were enrolled across the 3 studies; of these, 1,512 were treatment-naïve, 440 were treatment experienced and 224 had compensated cirrhosis. Of the 1,518 patients randomized to the 12-week arms of ION-1 and to all arms of ION-2 and ION-3, 1,456 patients (95.9%) achieved the primary efficacy endpoint of SVR12. Of the 62 patients (4.1%) who failed to achieve SVR12, 36 patients (2.4%) experienced virologic failure: 35 due to relapse and only one patient due to on-treatment breakthrough (with documented noncompliance). Twenty-six patients (1.7%) were lost to follow-up or withdrew consent [10].
19/12/2013 21:49:46 |
May 13: NCT01851330 (ION-3) starts May 13 and is due to complete Dec 14 [9].
13/05/2013 09:13:20 |
May 13: Company is to start a 3rd PIII trial (ION-3) of the once daily fixed-dose combination tablet of sofosbuvir and ledipasvir in 600 non-cirrhotic, treatment-naïve genotype 1 HCV-infected patients. The design of ION-3 is based on interim results from the PII LONESTAR study, which eva luated 8- and 12-week courses of therapy in 60 treatment-naïve, non-cirrhotic patients. In this study, 19/19 patients in the 12-week arm had a sustained virologic response four weeks after completing therapy (SVR4) and 40/41 in the 8-week arms had a SVR8, with one relapse occurring in the arm receiving sofosbuvir/ledipasvir without RBV. In ION-3, participants will be randomized to receive sofosbuvir and ledipasvir for 8 weeks (n=200), sofosbuvir and ledipasvir + RBV for 8 weeks (n=200), or sofosbuvir and ledipasvir for 12 weeks (n=200). The primary endpoint is SVR12, defined as maintaining undetectable HCV RNA 12 weeks post-treatment and considered a cure for HCV infection. The study is designed to assess non-inferiority of the 8-week treatment duration arms to the 12-week treatment duration arm [8].
03/05/2013 08:43:40 |
Mar 13: A planned review by the study´s Data and Safety Monitoring Board (DSMB) of safety data from 200 pts in all four arms and of SVR4 rates (sustained virologic response four weeks after completion of therapy) from 100 pts in the two 12-week duration arms concluded that the ION-1 trial should continue without modification [7].
05/04/2013 09:35:12 |
Jan 13: NCT01768286 (ION-2) is a PIII, multicentre, randomized, open-label study to investigate the efficacy and safety of sofosbuvir/GS-5885 fixed-dose combination (400/90 mg) ± ribavirin for 12 and 24 weeks in 400 treatment-experienced subjects with chronic Genotype 1 HCV Infection. The primary outcomes are SVR12 and safety and tolerability. The study starts Jan 13 and is due to complete Nov 14 [4].
24/01/2013 17:22:13 |
Oct 12: NCT01701401 is a PIII, multicentre, randomized, open-label study to investigate the efficacy and safety of sofosbuvir/GS-5885 fixed-dose combination (400/90 mg) +/- ribavirin for 12 and 24 weeks in 800 treatment-naive subjects with chronic genotype 1 HCV Infection. The primary outcome is sustained virologic response (SVR) 12 weeks after discontinuing therapy. The study starts Oct 12 and is due to complete Dec 14 [2].
08/10/2012 17:56:34 |
Jul 12: Gilead is planning to start a PIII study of the combination of GS-7977 + GS-5855 in a single pill to treat hepatitis C in a trial of 800 patients by Q4 2012. If the combination is effective, the company could apply for regulatory approval in the middle of 2014 [1].
31/07/2012 08:41:11 |
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Evidence Based eva luations |
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NHSC/NIHR |
http://www.hsc.nihr.ac.uk/topics/sofosbuvir-with-ledipasvir-for-hepatitis-c-genotyp/ |
