All Journal Entries Journals
Sort By:  

EASL 2013, International Liver Conference, AbbVie

Apr 28, 2013 - 0 comments
Tags:

EASL 2013

,

International Liver Conference

,

ABT 450/r

,

ABT 267

,

ABT 333



AbbVie reported results of a trial involving a 12 week regimen of 3 drugs combined with RBV trials (90% SVR12):

New Data from AbbVie's Phase IIb Aviator Trial Demonstrate High Sustained Viral Response Rates Across Multiple Patient Types with HCV Genotype 1

- 96 percent of treatment-naive patients and 93 percent of prior null responders treated with AbbVie's investigational IFN-free, triple-DAA combination therapy achieve SVR24

- Additional analyses looks at response rates in patients with differing baseline factors including gender, viral load and fibrosis stage

Apr 23, 2013

AMSTERDAM, April 23, 2013 /PRNewswire/ -- (NYSE: ABBV)  – Results from "Aviator,"  AbbVie's phase IIb clinical trial of its investigational direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) infection, continue to demonstrate high sustained viral response (SVR) rates against genotype 1 HCV, across patient types. Data show greater than 90 percent SVR were achieved in patients new to treatment and in patients who had previously failed treatment with pegylated interferon and ribavirin (null responders). In addition, similar high SVR rates observed after 12 and 24 weeks of treatment in the Phase IIb trial reinforce the adequacy of the 12-week treatment duration for the investigational interferon-free, triple DAA combination.  The triple-DAA combination is currently being studied in Phase III clinical trials. Results will be featured in the official press conference at the 2013 International Liver Congress® (ILC) in Amsterdam on Wednesday, April 24 at 11:00 CEST and presented on Thursday, April 25.

"These new results from the Aviator study further demonstrate that this investigational all-oral therapy combination can achieve high sustained viral response after 12 weeks of treatment," said Kris Kowdley, M.D., Director of the Liver Center of Excellence and Director of Research in the Digestive Disease Institute at Virginia Mason Medical, and Clinical Professor of Medicine at the University of Washington in Seattle. "The consistency of high sustained viral response rates that we have seen in clinical trials across populations is encouraging, especially given the proportion of patients with these characteristics who have failed with interferon plus ribavirin treatment."
"AbbVie's clinical development program aims to improve virologic cure rates, including in patients who have historically been harder to treat with current therapies, such as prior null responders. While further studies are required to confirm these findings, we remain encouraged by the high viral response rates and the safety profile we have seen in the Aviator study," said Barry Bernstein, divisional vice president, infectious disease development, AbbVie. "Our Phase III trials are progressing well and we remain focused on bringing an interferon-free treatment option to patients with HCV genotype 1 infection."

About Study M11-652 (Aviator)
The objective of this phase 2b study was to assess the safety, and efficacy of ABT-450/r (dosed 100/100 to 200/100mg once daily), ABT-267 (25mg once daily), ABT-333 (400mg twice daily) and ribavirin in non-cirrhotic treatment-naive patients and prior peg-interferon/ribavirin null responders administered for 8, 12 or 24 weeks. Enrollment was open to GT1-infected patients regardless of IL28B host genotype and ribavirin dosing was weight-based.

A summary of key data from the trial is below:
Treatment-Naive Null Responders
Duration 8 weeks 12 weeks 24 Weeks 12 weeks 24 weeks
Regimen ABT-450/r
ABT-267
ABT-333
RBV ABT-450/r

ABT-333
RBV ABT-450/r
ABT-267

RBV ABT-450/r
ABT-267
ABT-333
ABT-450/r
ABT-267
ABT-333
RBV ABT-450/r
ABT-267
ABT-333
RBV ABT-450/r
ABT-267

RBV ABT-450/r
ABT-267
ABT-333
RBV ABT-450/r
ABT-267
ABT-333
RBV
Number dosed 80 41 79 79 79 80 45 45 43
Breakthrough 0 1 1 1 0 0 0 3 1
Relapse 10 4 8 5 1 2 5 0 0
SVR12 (ITT) 89% 85% 91% 90% 99% 93% 89% 93% 98%
SVR24 (ITT) 88% 83% 89% 87% 96% 90% 89% 93% 95%
For the 12-week triple-DAA regimen with ribavirin being studied in Phase 3 trials:
• 99% of treatment-naive patients achieved SVR12, 96% achieved SVR24 in this intent-to-treat analysis
• 93% of prior null responders achieved SVR12 and SVR24
• The single relapse with this regimen occurred at post-treatment week two
With the triple-DAA plus ribavirin regimen, comparable SVR24 response rates were also seen in treatment naive patients and null responder patients across HCV subtype, IL28B genotype and baseline HCV-RNA levels and severity of fibrosis.  

SVR24 by patient subtype in the "Aviator" study

Characteristic Treatment Naive Null Responders
GT1a 91% (n=108) 93% (n=55)
GT1b 98% (n=50) 97% (n=33)
Non-CC  IL28B genotype 95% (n=115) 94% (n=85)
CC IL28B genotype 89% (n=44) 100% (n=3)
Viral Load (≥7 log) 89% (n=35) 91% (n=22)
Viral load (<7 log) 94% (n=124) 96% (n=66)
Fibrosis Stage (F0-F1)* 94% (n=113) 95% (n=41)
Fibrosis Stage (F2-F3)* 91% (n=42) 93% (n=45)
Male 92% (n=78) 93% (n=55)
Female 94% (n=81) 97% (n=33)

*The fibrosis analysis was post-hoc based on biopsy or non-invasive testing at screening.
The safety profile seen in this study is consistent with the initial presentation of results in November 2012. Of the 247 patients included in this analysis, four patients (1.6 percent) discontinued the study because of drug-related adverse events.  Serious adverse events were noted in 4 patients (1.6 percent), with one (arthralgia) considered possibly drug-related.  Other events reported in more than 10 percent of patients included headache, fatigue, nausea, insomnia, and diarrhea.  Grade 3-4 laboratory abnormalities in total bilirubin (six patients) and ALT (one patient) were noted; all resolved with continued dosing.

About Study M11-652 (Aviator)
The objective of this phase 2b study was to assess the safety, and efficacy of ABT-450/r (dosed 100/100 to 200/100mg once daily), ABT-267 (25mg once daily), ABT-333 (400mg twice daily) and ribavirin in non-cirrhotic treatment-naive patients and prior peg-interferon/ribavirin null responders administered for 8, 12 or 24 weeks. Enrollment was open to GT1-infected patients regardless of IL28B host genotype and ribavirin dosing was weight-based.

About the Hepatitis C Virus  
Across the world, about 160 million people are chronically infected with hepatitis C.1 Hepatitis C is an inflammation of the liver caused by an infection with the hepatitis C virus (HCV).2  HCV is transmitted when an infected person's blood enters the bloodstream of another person.3
For the hepatitis C virus, there are six major HCV genotypes (GT1-6).4 Presently, there is no vaccine for the hepatitis C virus (HCV) infection.3 Decision to treat is dependent on a number of factors such as the amount of liver damage present, other conditions the patient may have, amount of virus in the body, and viral genotype.4 If treatment is needed, a hepatitis C infection is typically treated with a combination of antivirals.3
About AbbVie's HCV Development Programs

AbbVie's HCV portfolio includes investigational medicines with three different mechanisms of action, including protease (ABT-450/r), polymerase (ABT-333) and NS5A (ABT-267) inhibitors, currently being studied in clinical trials. ABT-450 is being developed with low dose ritonavir which enhances the pharmacokinetic properties of ABT-450. The use of ritonavir 100mg with ABT-450 for the treatment of HCV is investigational.
ABT-450 was discovered during the course of a collaboration between AbbVie and Enanta Pharmaceuticals for HCV protease inhibitors and regimens that include protease inhibitors. ABT-450 is being developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of HCV. AbbVie is well-positioned to explore combinations and co-formulations of these medicines.

Ritonavir Use in the Treatment of HIV
Ritonavir is in a class of medicines called the HIV protease inhibitors. Ritonavir is used in combination with other anti-HIV medicines to treat people with human immunodeficiency virus (HIV) infection. Ritonavir is for adults and for children greater than 1 month in age and older.
Ritonavir does not cure HIV infection or AIDS and does not reduce the risk of passing HIV to others. People taking ritonavir may still get opportunistic infections or other conditions that happen with HIV infection. Some of these conditions are pneumonia, herpes virus infections, and Mycobacterium avium complex (MAC) infections.

Ritonavir Safety in Treatment of HIV
Patients should not take ritonavir with certain medicines, as these can cause serious or life-threatening problems such as irregular heartbeat, breathing difficulties, or excessive sleepiness. Patients should not take ritonavir if they have had a serious allergic reaction to any of its ingredients. Some patients taking ritonavir may develop liver and pancreas problems, which can cause death.

Patients may develop large increases in triglycerides and cholesterol, diabetes, high blood sugar, changes in body fat, increased bleeding in people with hemophilia, allergic reactions, and/or changes in heart rhythm. Patients may develop signs and symptoms of infections that they already have after starting anti-HIV medicines.

http://abbvie.mediaroom.com/2013-04-23-New-Data-from-AbbVies-Phase-IIb-Aviator-Trial-Demonstrate-High-Sustained-Viral-Response-Rates-Across-Multiple-Patient-Types-with-HCV-Genotype-1

++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++


Interferon-free, triple-DAA regimen safe, effective for chronic HCV
April 26, 2013

Nearly all patients with chronic hepatitis C treated with an interferon-free drug regimen for 12 or 24 weeks experienced sustained virologic response in a study presented at the International Liver Congress in Amsterdam.

Researchers administered 100-200 mg HCV protease inhibitor ABT-450 (AbbVie) with 100 mg ritonavir (ABT-450/r) once daily to patients with chronic hepatitis C genotype 1, along with 25 mg NS5A inhibitor ABT-267 once daily and 400 mg non-nucleoside NS5B inhibitor ABT-333 twice a day, and weight-based ribavirin, for 12 or 24 weeks. The cohort included 79 12-week and 80 24-week recipients among treatment-naive patients, and 45 12-week and 43 24-week recipients among previous nonresponders. Patients were either treatment-naive or nonresponsive to prior pegylated interferon/ribavirin therapy.

Sustained virologic response (SVR) rates at 4 weeks among treatment-naive participants were 98.7% in the 12-week and 96.2% in the 24-week group. Among prior nonresponders, SVR4 rates were 93.3% in the 12-week and 97.7% in the 24-week groups.

Among treatment-naive patients, SVR12 was 99% in the 12-week and 93% in the 24-week group, while nonresponders experienced SVR12 in 93% of 12-week and 98% of 24-week cases. SVR24 was achieved by 96% of 12-week and 90% of 24-week treatment-naive participants and 93% of 12-week and 95% of 24-week nonresponders. Across the cohort, SVR was similar regardless of IL28B genotype, baseline HCV RNA levels, fibrosis stage and infection with HCV genotype 1a compared with 1b.

Commonly reported events included headache, fatigue, insomnia, diarrhea and nausea. Four patients withdrew from the study after experiencing serious adverse events.

“The consistency of high sustained viral response rates that we have seen in clinical trials across populations is encouraging, especially given the proportion of patients with these characteristics who have failed with interferon plus ribavirin treatment,” researcher KrisV. Kowdley, MD, director of research at the Digestive Disease Institute at Virginia Mason Medical Center in Seattle, said in a press release.

Phase 3 trials are under way for the 12-week regimen.

http://hepatitiscnewdrugs.blogspot.com/2013/04/easl-interferon-free-triple-daa-regimen.html



EASL 2013, International Liver Conference, Janssen

Apr 28, 2013 - 1 comments
Tags:

EASL 2013

,

International Liver Conference

,

simeprevir



Janssen R & D (Ireland) reported results of two Phase 3 trials, G1 & G2, treatment naive, simeprevir.

EASL: Janssen Presents New Data from Simeprevir phase III studies Quest 1 and 2 in hepatitis C patients  
Findings from Two Phase 3 Studies of Janssen's Simeprevir Administered Once Daily Demonstrate Sustained Virologic Response in Genotype 1 Chronic Hepatitis C Patients  

AMSTERDAM, April 23, 2013 /PRNewswire/ -- Janssen R&D Ireland (Janssen) today announced primary efficacy and safety results from two global Phase 3 studies demonstrating that use of the investigational protease inhibitor simeprevir (TMC435) led to sustained virologic response 12 weeks after the end of treatment (SVR12) in 80 and 81 percent, respectively, of treatment-naive genotype 1 chronic hepatitis C adult patients with compensated liver disease, including all stages of liver fibrosis, when administered once daily with pegylated interferon and ribavirin. In both studies, 50 percent of patients receiving pegylated interferon and ribavirin alone achieved SVR12.

The data will be presented this week at The International Liver Congress 2013 of the European Association for the Study of the Liver (EASL) in Amsterdam, The Netherlands. The QUEST-1 and QUEST-2 data will be discussed in an official EASL press conference on April 24 at 11:00 a.m. CEST.

"More than 390 treatment-naive genotype 1 hepatitis C patients in 39 countries received simeprevir as part of the Phase 3 QUEST trials," said Michael Manns, M.D., professor and chairman, Department of Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover. "I am pleased to be a part of these robust studies and look forward to seeing the results from upcoming trials of simeprevir in treatment-experienced patients later this year."

In QUEST-1 and QUEST-2, patients were randomized to receive simeprevir or placebo for 12 weeks plus pegylated interferon and ribavirin for 24 or 36 weeks. In findings related to a secondary endpoint, 85 percent (QUEST-1) and 91 percent (QUEST-2) of patients receiving simeprevir were able to shorten therapy with pegylated interferon and ribavirin to 24 weeks due to meeting response-guided therapy (RGT) criteria. Of those patients meeting RGT criteria to stop treatment at 24 weeks, 91 percent (QUEST-1) and 86 percent (QUEST-2) of patients achieved SVR12.

"Given the long-term health risks associated with hepatitis C, it's important that physicians and patients have multiple options to treat the disease," said Ira Jacobson, M.D., chief of the Division of Gastroenterology and Hepatology, Vincent Astor Distinguished Professor of Medicine, Weill Cornell Medical College, and attending physician, New York-Presbyterian Hospital/Weill Cornell Medical Center. "The results of these Phase 3 trials suggest that simeprevir could represent an important new treatment option for people living with genotype 1 chronic hepatitis C."

Patients enrolled in QUEST-1 and QUEST-2 were stratified by HCV genotype 1 subtype and IL28B genotype. In QUEST-1, SVR12 rates among patients treated with simeprevir with IL28B genotype variations were 94 percent for the CC allele, 76 percent for the CT allele, and 65 percent for the TT allele. In QUEST-2, SVR12 rates among patients treated with simeprevir with IL28B genotype variations were 96 percent for the CC allele, 80 percent for the CT allele, and 58 percent for the TT allele. Among patients with METAVIR scores F3 and F4, 70 percent of patients treated with simeprevir in QUEST-1 and 66 percent of patients treated with simeprevir in QUEST-2 achieved SVR12. Among patients with METAVIR scores F0 to F2, 83 percent of patients treated with simeprevir in QUEST-1 and 85 percent of patients treated with simeprevir in QUEST-2 achieved SVR12. The METAVIR score is used to quantify the degree of inflammation and fibrosis of the liver and patients are scored on a four-point scale.

"Patient response rates to hepatitis C therapy can be variable, depending on factors such as viral genotype and subtype, and liver fibrosis. Patients with genotype 1a, IL28B genotype TT and METAVIR scores of F3 and F4 can be particularly challenging to cure," said Maria Beumont, M.D., medical leader for simeprevir, Janssen. "Janssen is committed to advancing hepatitis C therapy for even the most difficult-to-cure patients."

The most common adverse events seen in patients receiving simeprevir in QUEST-1 were fatigue (42 percent versus 41 percent for placebo), itch (26 percent versus 16 percent for placebo), and headache (33 percent versus 39 percent for placebo). The most common adverse events seen in patients receiving simeprevir in QUEST-2 were fatigue (37 percent versus 42 percent for placebo), itch (25 percent versus 25 percent for placebo), headache (39 percent versus 37 percent for placebo), fever (31 percent versus 40 percent for placebo), and influenza-like illness (26 percent versus 26 percent for placebo). In QUEST-1, in both the simeprevir and placebo arms, 3 percent of patients discontinued treatment due to an adverse event. In QUEST-2, 2 percent of patients in the simeprevir arm and 1 percent of patients in the placebo arm discontinued treatment due to an adverse event.

About QUEST-1 and QUEST-2

QUEST-1 and QUEST-2 are global, Phase 3, randomized, double-blind, placebo controlled clinical trials assessing the efficacy, safety and tolerability of simeprevir plus pegylated interferon and ribavirin versus pegylated interferon and ribavirin alone in treatment-naive adult patients with genotype 1 chronic hepatitis C with compensated liver disease, including all stages of liver fibrosis.

In the QUEST-1 and QUEST-2 trials, 394 and 391 patients, respectively, were randomized to receive one 150 mg capsule of simeprevir or placebo once daily plus pegylated interferon and ribavirin for 12 weeks, followed by pegylated interferon and ribavirin alone for either 12 or 36 weeks based on RGT criteria. Patients in the simeprevir arm were considered to have met RGT criteria if their HCV RNA levels were <25 IU/mL (detectable or undetectable) at week 4 and <25 IU/mL undetectable at week 12. In patients meeting RGT criteria, HCV therapy was stopped at week 24. All other patients continued treatment until week 48.

About Simeprevir

Simeprevir (TMC435) is an investigational NS3/4A protease inhibitor jointly developed by Janssen and Medivir AB for the treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease, including all stages of liver fibrosis. Simeprevir is believed to work by blocking the protease enzyme that enables the hepatitis C virus to survive and replicate in host cells. Janssen recently announced the submission of new drug applications for simeprevir in Japan and the United States for the treatment of genotype 1 hepatitis C, and anticipates submitting simeprevir for regulatory authorization in the EU in the first half of 2013.

Global Phase 3 studies of simeprevir include QUEST-1 and QUEST-2 in treatment-naive adult patients, PROMISE in patients who have relapsed after prior interferon-based treatment and ATTAIN in null-responder adult patients. In parallel to these trials, Phase 3 studies for simeprevir are ongoing in treatment-naive and treatment-experienced HIV-HCV co-infected patients and HCV genotype 4 patients. To date, 1,846 patients have been treated with simeprevir in clinical trials.

http://hepatitiscnewdrugs.blogspot.com/2013/04/easl-medivir-presents-new-data-from.html




EASL 2013, International Liver Conference, Boehringer Ingelheim

Apr 28, 2013 - 0 comments
Tags:

EASL 2013

,

International Liver Conference

,

faldaprevir



Boehringer Ingelheim reported results of one Phase 3 trial, STARTVerso at the EASL 2013 International Liver Conference in Amsterdam.

EASL: Therapy Free of Side Effects of Other HCV Drugs  
Therapy Free of Side Effects of Other HCV Drugs

By Michael Smith, North American Correspondent, MedPage Today

Published: April 25, 2013

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

AMSTERDAM – An investigational protease inhibitor (PI) led to viral cures in about four out of five hepatitis C virus (HCV) patients, a researcher reported here.

In a phase III study, either of two doses of faldaprevir combined with pegylated interferon and ribavirin significantly outperformed placebo, according to Peter Ferenci, MD, of the Medical University of Vienna.

But importantly, Ferenci told MedPage Today during the meeting of the European Association for the Study of the Liver, they did so without the side effects associated with earlier drugs in the class.
The efficacy results are "indeed very good," commented Mark Thursz, MD, of St. Mary's Hospital in London, who was not involved in the study but who moderated a press conference at which some details were discussed.

Action Points
Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal
An investigational protease inhibitor (faldaprevir) led to viral cures in about four out of five hepatitis C virus (HCV) patients, a study found.
Note that faldeprevir was well-tolerated without the side effects associated with earlier protease inhibitor drugs.

But the most important aspect of the results, Thursz said, is the safety profile of the drug. "This will be far better tolerated by our patients in the clinic than the earlier PIs," he told reporters.

Research is underway to see if faldaprevir, in combination with other oral direct-acting HCV drugs, can be effective in the absence of interferon and possibly without interferon or ribavirin.

In the current study, investigators enrolled 652 patients with genotype 1 HCV and randomly assigned them for 24 weeks to get placebo or either 120 or 240 milligrams of faldaprevir daily. All patients also got then-standard therapy with interferon and ribavirin.

Patients with what the investigators called "early treatment success" – defined as low levels of HCV at week 4 and undetectable levels at week 8 – were eligible to stop treatment at week 24, while others got another 24 weeks of interferon and ribavirin.

In the placebo arm, 22% of patients had early treatment success, Ferenci reported, compared with 87% in the low-dose faldaprevir arm and 89% in the high-dose arm, and stopped treatment at 24 weeks.

The primary endpoint of the study was 12-week sustained virologic response (SVR12) – no detectable HCV RNA 12 weeks after the end of treatment.

The investigators found that 52% of patients in the placebo arm reached that endpoint, similar to historical results. In the low-dose faldaprevir arm, the SVR12 rate was 79%, compared with 80% in the high-dose arm (P<0.0001 for both).

The only adverse event clearly caused by the drug, Ferenci said, was an elevation in bilirubin, but that was not associated with elevated liver enzymes and had "no clinical significance."
Some patients reported rash but did not need medical attention for it, he added.

Indeed, he said, the rates of most observed adverse events, including those regarded as serious, were similar among the arms, with little difference in discontinuations owing to adverse events.

http://hepatitiscnewdrugs.blogspot.com/2013/04/easl-therapy-free-of-side-effects-of.html




EASL 2013, International Liver Conference, Gilead

Apr 28, 2013 - 0 comments
Tags:

Sofosbuvir

,

EASL 2013

,

International Liver Conference



Gilead reported results on four phase 3 trials with sofosbuvir at EASL 2013, International Liver Conference.

Data from Phase 3 Studies of Gilead’s Sofosbuvir for Hepatitis C To Be Presented at 48th Annual EASL Meeting; Findings Published Online Today in The New England Journal of Medicine

AMSTERDAM--(BUSINESS WIRE)--Apr. 23, 2013-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that detailed results from four Phase 3 clinical trials (NEUTRINO, FISSION, POSITRON and FUSION) evaluating sofosbuvir, the company’s investigational once-daily nucleotide NS5B inhibitor for the treatment of chronic hepatitis C virus (HCV) infection, will be presented this week in oral sessions at the 48th Annual Meeting of the European Association for the Study of the Liver (International Liver Congress 2013) in Amsterdam, The Netherlands. In addition, detailed results from the four clinical studies have also been published online in two papers, ahead of print, in The New England Journal of Medicine (NEJM).

In the four trials, sofosbuvir was administered to nearly 1,000 patients with chronic HCV infection as part of an all-oral 12-week or 16-week treatment regimen in combination with ribavirin (RBV) in genotypes 2 and 3, or with RBV and pegylated interferon (peg-IFN) for 12 weeks in genotypes 1, 4, 5 and 6. Overall SVR12 rates (sustained viral response 12 weeks after completing therapy) from 50 to 90 percent were observed. Patients who achieve SVR12 are considered cured of their HCV infection.
A description of the four Phase 3 studies and SVR12 results are summarized in the table below. Detailed results from the Phase 3 studies of sofosbuvir are available at www.nejm.org/online-first.
  
Sofosbuvir Phase 3 Studies
Study    Population    Treatment groups    SVR12 Rates
NEUTRINO    Genotype 1/4/5/6 treatment-naïve    Sofosbuvir + RBV + Peg-IFN for 12 weeks    90% (295/327)
FISSION    Genotype 2/3 treatment-naïve    Sofosbuvir + RBV for 12 weeks or    67% (170/253)
      Peg-IFN + RBV for 24 weeks    67% (162/243)
POSITRON Genotype 2/3, IFN intolerant, ineligible or unwilling Sofosbuvir + RBV for 12 weeks or 78% (161/207)
      Placebo for 12 weeks    0% (0/71)
FUSION Genotype 2/3 treatment-experienced Sofosbuvir + RBV for 12 weeks or 50% (50/100)
      Sofosbuvir + RBV for 16 weeks    73% (69/95)
  
“There remains an urgent unmet medical need for individuals diagnosed with chronic hepatitis C infection,” commented Ira Jacobson , MD, Chief of the Division of Gastroenterology and Hepatology, Vincent Astor Distinguished Professor of Medicine, The Joan Sanford I. Weill Medical College of Cornell University, Attending Physician, New York-Presbyterian Hospital Cornell Campus. “The breadth of data from the Phase 3 program evaluating sofosbuvir will help physicians understand how to treat the disease in the future across various HCV genotypes and patient populations.”

“In these particular studies, sofosbuvir-based HCV therapy demonstrated high efficacy rates and a favorable safety profile while reducing the need for interferon injections to 12 weeks, or eliminating interferon completely from the regimen,” said Eric Lawitz , MD, President and Medical Director, The Texas Liver Institute, University of Texas Health Science Center, San Antonio. “Based on these findings, sofosbuvir, once approved, has the potential to play an important role in addressing the global hepatitis C epidemic.”

The NS5b region of the HCV viral genome for all patients who relapsed was sequenced and no S282T mutations were observed by population or deep sequencing (1 percent cutoff). There was no change in susceptibility to sofosbuvir or RBV observed by phenotypic analyses.

With the exception of one patient in FISSION who was non-compliant, relapse accounted for all virologic failures. Adverse events were generally mild and included fatigue, nausea, headache, insomnia, pruritis, anemia and dizziness. Less than 2 percent of patients in the sofosbuvir treatment groups discontinued due to adverse events.
On April 8, Gilead submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for sofosbuvir for the treatment of HCV infection. The data submitted in the NDA support the use of sofosbuvir and RBV as an all-oral therapy for patients with genotype 2 and 3 HCV infection, and for sofosbuvir in combination with RBV and peg-IFN for treatment-naïve patients with genotype 1, 4, 5 and 6 HCV infection.

Gilead plans to file for regulatory approval of sofosbuvir in other geographies, including the European Union, in the second quarter of 2013. The European Medicines Agency (EMA) has accepted Gilead’s request for accelerated assessment for sofosbuvir, a designation that is granted to new medicines of major public health interest. Accelerated assessment could shorten the EMA’s review time of sofosbuvir by two months. Granting of accelerated assessment does not guarantee a positive opinion from the CHMP or approval by the European Commission.

About Sofosbuvir
Sofosbuvir is a nucleotide analogue inhibitor of the HCV NS5B protein, which plays an essential role in HCV replication. Sofosbuvir is a direct-acting agent, meaning that it interferes directly with the HCV life cycle by suppressing viral replication. Sofosbuvir is intended to become a cornerstone of interferon-free, all-oral treatment regimens for HCV that achieve higher cure rates more rapidly and with fewer side effects than current therapeutic options. Sofosbuvir is an investigational product and its safety and efficacy have not yet been established.

http://www.gilead.com/news/press-releases/2013/4/data-from-phase-3-studies-of-gileads-sofosbuvir-for-hepatitis-c