EASL:Hepatitis C-NEW DATA SUGGESTS INTERFERON-FREE THERAPY AROUND THE CORNER

NEW DATA SUGGESTS INTERFERON-FREE THERAPY AROUND THE CORNER FOR HCV PATIENTS

Further data shows PegIFN-λ’s comparable efficacy but better safety profile than PegIFN-α

Barcelona, Spain, 19 April 2012 /PRNewswire/ — New data presented at the International Liver Congress™ 2012 shows consolidation of the interferon-free (IFN) revolution in HCV treatment. The much anticipated data from a number of clinical trials 1,2,3,4,5,6 confirm that combinations of antivirals offer the hope of shorter, more effective treatment with fewer side effects.

The following new studies cover the treatment of HCV patients with genotypes (GT) 1, 2 or 3, who were administered ribavirin (RBV) - without IFN - and either one or two other drugs: direct-acting antivirals HCV nucleotide analogues, HCV protease inhibitors, non-nucleoside RNA polymerase inhibitors – or host-targeting antivirals cyclophilin A inhibitor.

PROTON & ELECTRON
•Lawitz E, et al ‘PSI-7977 PROTON and ELECTRON: 100% concordance of SVR4 with SVR24 in HCV GT1, GT2, & GT3’ and the related abstract Gane EJ, et al ‘ELECTRON: once daily PSI-7977 plus RBV in HCV GT1/2/3’.
•In Lawitz E, et al, 100% of HCV GT2 or 3 patients (10) achieved SVR4 after treatment with PSI-7977 and RBV. In Gane EJ, et al, of nine HCV GT1 prior null-responders treated with PSI-7977 and RBV for 12 weeks, 7 had undetectable levels of HCV RNA by week 2.

SOUND-C2
•Zeuzem S, et al ‘SVR4 and SVR12 with an INTERFERON-FREE regimen of BI201335 and BI207127, +/- RIBAVIRIN, in treatment-naïve patients with chronic genotype-1 HCV infection: interim results of SOUND-C2’.
•Treatment-naïve GT1 HCV patients treated with a regimen of BI201335, BI207127 and RBV achieved 60% SVR12 after 16 weeks of treatment and up to 70% SVR4 after treatment with a lower BI207127 dose (600mg BID) for 28 weeks.

VITAL-1
•Pawlotsky J-M, et al ‘ALISPORIVIR plus RIBAVIRIN is highly effective as INTERFERON-FREE or INTERFERON-ADD-ON regimen in previously untreated HCV-GT2 or GT3 patients: SVR12 results from VITAL-1 phase 2b study’ and the related abstract Alberti A, et al ‘ALISPORIVIR (ALV) plus PEG-INTERFERON/RIBAVIRIN (PR) in HCV G1 treatment-experienced patients achieves primary endpoint with superior efficacy at treatment week 12 compared to retreatment with PR’.
•In Pawlotsky J-M, et al, 88% of treatment-naïve HCV GT2 or 3 patients achieved SVR 12 after treatment with Alisporivir and RBV. In Alberti A, et al, 70% of null non-responders achieved cEVR when treated with Alisporivir, IFN and RBV.

AI444040
•Sulkowski M, et al ‘Potent viral suppression with all-oral combination of DACLATASVIR (ns5a inhibitor) and GS-7977 (ns5b inhibitor), +/-RIBAVIRIN, in treatment-naïve patients with chronic HCV GT1, 2, or 3’
•Treatment-naïve HCV GT1, 2, and 3 patients given an IFN- and RBV-free once-daily combination of DACLATASVIR and GS-7977 for 24 weeks achieved high rates of early virologic response (HCV RNA detectable at week 4 but undetectable at week 12 EVR) by mITT analysis: 97% EVR in GT1, 90% in GT2 and 3.

The combination of PegIFN-α and ribavirin (RBV) is the current standard of care for chronic HCV7, but is associated with a number of side effects – including flu-like symptoms, psychiatric manifestations, autoimmune reactions, and hematologic toxicities.8,9 Between 20-40% of patients require a dose reduction or temporary interruption in their PegIFN-α and ribavirin (RBV) treatment10 and in 10-14% of patients, side effects are so severe that treatment must be discontinued.8,9

However, studies have shown that achieving a virologic response in chronic HCV is much more dependent on the dose of IFN-α11/PegIFN-α12,13,14 than RBV15,16,17,11,18. As such, PegIFN-α free therapy is highly anticipated by healthcare professionals and patients alike.

EASL’s Secretary General Professor Mark Thursz commented on the exciting new data being showcased at the congress: “In the future, patients can look forward to all oral treatment regimens with high success rates and low side effects. Furthermore, there is a large cohort of patients with more advanced liver disease who will now be able to access treatment that was previously impossible due to the side effects of Interferon-alpha. Over the last five years we have seen an evolution in HCV treatment, with direct antivirals used in combination with Pegylated Interferon and Ribavirin. Interferon-free regimes truly represent a revolution in treatment.”

Separate data presented at the congress may provide a further option. New results from a phase IIb study show a different form of interferon pegylated Interferon-lambda (PegIFN-λ) – administered with RBV for 24 weeks in HCV GT2 & 3 patients gives comparable SVR24 (undetectable HCV RNA levels 24 weeks after treatment) to PegIFN-α-2a and RBV, but with fewer side effects (musculoskeletal and flu-like symptoms, hematologic toxicity) and dose modifications for PegIFN or RBV.

EASL’s Secretary General Professor Mark Thursz commented: “It remains possible that a number of patients will still need interferon based therapy for their HCV infection. Interferon-lambda, with a better side effect profile, looks like an excellent option in this group of patients, who are likely to have more advanced disease.”

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