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

April 18, 2012

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

Further data shows PegIFN-lambda’s comparable efficacy but better safety

profile than PegIFN-alpha

New data presented at the International Liver Congress(TM) 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-naive patients with chronic
          genotype-1 HCV infection: interim results of SOUND-C2'.
        - Treatment-naive 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-naive 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-naive patients with chronic HCV GT1, 2, or 3'
        - Treatment-naive 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-alpha 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-alpha 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-alpha[11]/PegIFN-alpha[12],[13],[14] than
RBV[15],[16],[17],[11],[18]. As such, PegIFN-alpha 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-lambda) – administered with RBV for 24 weeks in HCV GT2 & 3 patients gives
comparable SVR24 (undetectable HCV RNA levels 24 weeks after treatment) to PegIFN-alpha-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
          [http://www.easl.eu/_the-international-liver-congress/general-information ](TM) which
          is the main scientific and professional event in hepatology worldwide
        - Meetings [http://www.easl.eu/_events ] including Monothematic and Special
          conferences, Post Graduate courses and other endorsed meetings that take place
          throughout the year
        - Clinical and Basic Schools of Hepatology [http://www.easl.eu/_education ], a
          series of events covering different aspects in the field of hepatology
        - Journal of Hepatology [http://www.easl.eu/members/journal-of-hepatology ]
          published monthly
        - Participation in a number of policy initiatives at European level
        - iLiver iPhone app [http://www.iliver.eu ] - a free medical app developed by
          EASL, with content fully authored, validated and accredited by 42 independent liver
          specialists

About The International Liver Congress(TM) 2012

The International Liver Congress(TM) 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(TM) 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(TM) 2012.

3. Zeuzem S, et al, SVR4 and SVR12 WITH AN INTERFERON-FREE REGIMEN OF BI201335 AND
BI207127, +/- RIBAVIRIN, IN TREATMENT-NAIVE PATIENTS WITH CHRONIC GENOTYPE-1 HCV
INFECTION: INTERIM RESULTS OF SOUND-C2. Abstract presented at the International Liver
Congress(TM) 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(TM) 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(TM) 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-NAIVE PATIENTS WITH CHRONIC HCV GT1, 2, OR 3. Abstract presented at the
International Liver Congress(TM) 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-NAIVE PATIENTS WITH HCV GENOTYPES (G) 2 or 3: FIRST SVR24
RESULTS FROM EMERGE PHASE IIB. Abstract presented at the International Liver Congress(TM)
2012.

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

        Email: easlpressoffice@cohnwolfe.com
        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


Source: PR Newswire