New Data Suggests Interferon-Free Therapy Around the Corner for HCV Patients

BARCELONA, Spain, April 19, 2012 /PRNewswire/ --

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

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.

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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 HCV^[7], 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) treatment^[10] 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-α^[11]/PegIFN-α^{[12],[13],[14]} than RBV^{[15],[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^[19] 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.

Professor 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."

Notes to Editors

About EASL

EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.

EASL's main focus on education and research is delivered through numerous events and initiatives, including:

• The International Liver Congress™ which is the main scientific and professional event in hepatology worldwide
• Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
• Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
• Journal of Hepatology published monthly
• Participation in a number of policy initiatives at European level
• iLiver iPhone app - a free medical app developed by EASL, with content fully authored, validated and accredited by 42 independent liver specialists

About The International Liver Congress™ 2012

The International Liver Congress™ 2012, the 47th annual meeting of the European Association for the study of the Liver, is being held at the Centre Convencions Internacional (CCIB) in Barcelona from April 18 - 22, 2012. The congress annually attracts over 8,300 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.

References

1. Lawitz E, et al, PSI-7977 PROTON and ELECTRON: 100% CONCORDANCE OF SVR4 WITH SVR24 IN HCV GT1, GT2, & GT3. Abstract presented at the International Liver Congress™ 2012.

2. Gane EJ, et al, ELECTRON: ONCE DAILY PSI-7977 PLUS RBV IN HCV GT1/2/3. Abstract presented at the International Liver Congress™ 2012.

3. 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. Abstract presented at the International Liver Congress™ 2012.

4. 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. Abstract presented at the International Liver Congress™ 2012.

5. 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. Abstract presented at the International Liver Congress™ 2012.

6. 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. Abstract presented at the International Liver Congress™ 2012.

7. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatitis C virus infection. Journal of Hepatology 2011 vol. 55 245–264

8. Fried MW, et al, Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002 Sep 26;347(13):975-82.

9. Manns MP, et al, Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001 Sep 22;358(9286):958-65.

10. Jang JY and Chung RT, Chronic Hepatitis C. Gut Liver. 2011 June; 5(2): 117–132.

11. McHutchison JG, et al, Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C. Gastroenterology. 2002 Oct;123(4):1061-9.

12. Heathcote EJ, et al, Re-treatment of chronic hepatitis C with consensus interferon. Hepatology. 1998 Apr;27(4):1136-43.

13. Lindsay KL, et al, A randomized, double-blind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C. Hepatology. 2001;34:395–403.

14. Reddy KR, et al, Efficacy and safety of pegylated (40-kd) interferon alpha-2a compared with interferon alpha-2a in noncirrhotic patients with chronic hepatitis C. Hepatology. 2001;33:433–438.

15. Shiffman ML, et al, Treatment of chronic hepatitis C virus genotype 1 with peginterferon, ribavirin, and epoetin alpha. Hepatology. 2007;46:371–379.

16. Snoeck E, Wade JR, Duff F, Lamb M, Jorga K. Predicting sustained virological response and anaemia in chronic hepatitis C patients treated with peginterferon alfa-2a (40KD) plus ribavirin. Br J Clin Pharmacol. 2006;62:699–709.

17. Shiffman ML, Ghany MG, Morgan TR, et al. Impact of reducing peginterferon alfa-2a and ribavirin dose during retreatment in patients with chronic hepatitis C. Gastroenterology. 2007;132:103–112.

18. Hadziyannis SJ, Sette H, Jr, Morgan TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140:346–355.

19. Zeuzem S, et al, PEGINTERFERON LAMBDA-1a (LAMBDA) COMPARED TO PEGINTERFERON ALFA-2A (ALFA) IN TREATMENT-NAÏVE PATIENTS WITH HCV GENOTYPES (G) 2 or 3: FIRST SVR24 RESULTS FROM EMERGE PHASE IIB. Abstract presented at the International Liver Congress™ 2012.

For further information on the studies, or to request an interview, please do not hesitate to contact the EASL Press Office on:

Email: [email protected]
 
Travis Taylor   Onsite tel: +44(0)7894-386-422

Vicky O'Connor  Onsite tel: +44(0)7894-386-428

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SOURCE European Association for the Study of the Liver