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Last updated on April 19, 2014 at 13:20 EDT

INCIVO® (Telaprevir) SVR Rates Unaffected by Ribavirin Dose Reduction in Treatment Naïve and Previously Treated Patients With Genotype-1 Chronic HCV

April 18, 2012

BARCELONA, Spain, April 18, 2012 /PRNewswire/ –

– Retrospective sub-analyses from ADVANCE, ILLUMINATE and REALIZE Phase 3
studies will be presented at European Association for the Study of the Liver (EASL) 2012 -

Janssen Pharmaceutica NV (Janssen) will present new data for INCIVO (telaprevir) from
Phase 3 retrospective sub-analyses at the 47th annual meeting of the European Association
for the Study of the Liver (EASL) in Barcelona. The data shows that similar sustained
virologic response (SVR) rates were achieved regardless of ribavirin dose reduction,
including dose reduction to less than or equal to 600mg/day in a telaprevir-based
treatment regimen for both treatment naive and previously treated genotype-1 chronic HCV
patients.[1]

The study abstract is currently published online (http://www.easl.eu) and full
results will be presented on Saturday 21st April at 12:30pm CET.

The retrospective sub-analyses of the Phase 3 ADVANCE and ILLUMINATE trials evaluated
the impact of ribavirin dose reduction on SVR rates in treatment-naive genotype-1 chronic
HCV patients who received treatment with telaprevir in combination with peginterferon alfa
and ribavirin (T12PR) or peginterferon alfa and ribavirin alone (PR).[1] In the T12PR
arms, SVR was achieved by 74% (291/395) of patients who received a dose reduction to less
than or equal to 600mg and 75% (38/51) who received a ribavirin dose reduction to
800-1000mg/day, compared to 79% (346/439) of those who had no reduction in their ribavirin
dose.[1]

The retrospective sub-analysis of the Phase 3 REALIZE trial evaluated the impact of
ribavirin dose reduction on SVR rates of previously treated genotype-1 chronic HCV
patients who received treatment with telaprevir in combination with peginterferon alfa and
ribavirin (T12PR48) or peginterferon alfa and ribavirin alone (PR).[1] Results were
categorized according to patients’ previous response to treatment. For patients in the
T12PR48 arms who had relapsed previously on treatment with PR alone, SVR was achieved by
93% (27/29) of patients who received a dose reduction to less than or equal to 600mg and
83% (20/24) who received a ribavirin dose reduction to 800-1000mg/day, compared to 82%
(73/89) who had no reduction in their ribavirin dose. For patients who were prior partial
responders, SVR was achieved by 62% (8/13), 50% (1/2) and 66% (21/32) respectively and 25%
(2/8), 67% (2/3) and 31% (18/59) respectively for null responders. Analyses also examined
the timing of the ribavirin dose reduction and the duration of the reduction during the
studies and results were supportive of the study conclusions.[1]

These data suggest that timing, duration and extent of ribavirin dose reduction did
not substantially impact SVR in the telaprevir treatment arms. Since ribavirin dose
reduction was the mainstay of anemia management in the telaprevir development programme,
these data suggest that reducing the ribavirin dose did not impact SVR rates.

“We have seen significant advances in the treatment of HCV with the approved
direct-acting antivirals (DAAs), including telaprevir which has reported high SVR rates
for previously treated and treatment-naive adults with genotype-1 chronic HCV, however we
know management of side effects is still very important,” said Professor Mark Sulkowski,
Professor of Medicine, Johns Hopkins University School of Medicine, Baltimore. “These
results demonstrate that the reduction of ribavirin to help manage treatment-related
anaemia when treating with telaprevir did not compromise the chance of clearing the
virus.”

Ribavirin is a synthetic antiviral nucleoside analogue, co-administered with
peginterferon alfa to increase the efficacy of treatment for chronic HCV.[2] Anaemia is a
common side-effect of HCV treatment and can often be managed by the reduction of
ribavirin, among other management strategies.[2]

Jim Witek, Senior Medical Director, Janssen said “The results of these analyses
further support the efficacy of INCIVO in genotype-1 chronic HCV compared to PR alone,
even when ribavirin doses are reduced to help manage treatment-related anaemia. Janssen
remains dedicated to improving treatment options and outcomes for patients with HCV.”

About the Phase 3 retrospective sub-analyses

ADVANCE, ILLUMINATE and REALIZE were Phase 3 trials involving 2,290 patients to
evaluate the efficacy, safety and tolerability of telaprevir in combination with
peginterferon alfa and ribavirin in patients with genotype-1 chronic HCV.[3,4,5] In these
retrospective sub-analyses, the ADVANCE and ILLUMINATE patients who received 24 or 48
weeks total treatment with PR alone and 12 weeks of telaprevir (T12PR) were compared to
those who received 48 weeks of PR alone (PR).[1] In the REALIZE retrospective
sub-analysis, patients who received 48 weeks total treatment with PR alone (PR) were
compared to patients receiving the simultaneous start telaprevir-based regimen (T12PR48):
12 weeks of telaprevir and PR plus 36 weeks PR alone.[1] Patients who took erythropoietin
stimulating agents or did not have a hemoglobin measurement at baseline were excluded.
Efficacy outcomes were assessed based on ribavirin dose reductions in populations from
ADVANCE and ILLUMINATE, separately to those from the REALIZE trial.[1]

Among treatment-naive patients in ADVANCE and ILLUMINATE, 68% (604/885) who received
T12PR had a ribavirin dose reduction.[1] Among previously treated patients who received
T12PR48 in the REALIZE study, 38% (98/259) had a ribavirin dose reduction during the
overall treatment phase.[1] In all Phase 2 and 3 studies, anaemia occurred more commonly
in patients on a telaprevir-based regimen and led to discontinuation of all study drugs in
2.8%.[6]

Additional telaprevir data to be presented at EASL include:

        - Analysis showing that telaprevir in combination with peginterferon alfa
          and ribavirin is cost-effective for both treatment-naive and experienced patients,
          regardless of IL28B subtype, according to the threshold of GBP20,000-GBP30,000 per
          quality-adjusted life year (QALY)[7]

About INCIVO(R)

INCIVO(R) (telaprevir), in combination with peginterferon alfa and ribavirin, is
indicated for the treatment of genotype-1 chronic HCV in adult patients with compensated
liver disease (including cirrhosis) who are treatment naive, and who have previously been
treated with interferon alfa (pegylated or non pegylated) alone or in combination with
ribavirin, including relapsers, partial responders and null responders.[6] INCIVO is a
small molecule, selective inhibitor of the HCV serine protease, and a member of the new
class of medicine for the treatment of genotype-1 chronic HCV, direct acting antivirals
(DAAs). Unlike previous treatments, DAAs act directly on viral enzymes and prevent the
virus from replicating. INCIVO was approved by the European Commission on 19 September
2011.

Telaprevir was developed by Janssen-Virco BVBA, one of the Janssen Pharmaceutical
Companies, in collaboration with Vertex and Mitsubishi Tanabe Pharma. Janssen has rights
to commercialize telaprevir in Europe, South America, Australia, the Middle East and
certain other countries. Vertex has rights to commercialize telaprevir in North America
where it is being marketed under the brand name INCIVEK[TM]. Mitsubishi Tanabe Pharma has
rights to commercialize telaprevir in Japan and certain Far East countries where it is
being marketed as TELAVIC(R).

Important Safety Information

Please see full Summary of Product Characteristics or visit
http://www.ema.europa.eu for more details.

The overall safety profile of telaprevir is based on the Phase 2/3 clinical
development programme. In clinical trials, the incidence of adverse events of at least
moderate intensity was higher in the telaprevir group than in the placebo group (both
groups receiving peginterferon alfa and ribavirin). The most frequently reported moderate
adverse reactions (incidence greater than or equal to 5.0%) were anaemia, rash, pruritus,
nausea, and diarrhoea, and the most frequently reported severe adverse reactions
(incidence greater than or equal to 1.0%) were anaemia, rash, thrombocytopenia,
lymphopenia, pruritus, and nausea.[10]

Rash events were reported in 55% of patients with a telaprevir based regimen and more
than 90% of rashes were of mild or moderate severity. Severe rashes were reported with
telaprevir combination treatment in 4.8% of patients. Rash led to discontinuation in 5.8%
of patients. Anaemia was reported in 32.1% of patients and led to discontinuation in
2.8%.[10]

About HCV

HCV is a blood-borne infectious disease that affects the liver.[8,9] With an estimated
130-210 million people infected worldwide,[10] and three to four million people newly
infected each year, HCV puts a significant burden on patients and society.[11] Estimations
indicate that HCV caused more than 86,000 deaths and 1.2 million disability-adjusted
life-years (DALYs) in the WHO European region in 2002.[12] Chronic infection with HCV can
lead to liver cancer and other serious and fatal liver diseases.[13] About one-quarter of
the liver transplants performed in 25 European countries in 2004 were attributable to
HCV.[12] The previously accepted standard treatment for HCV is peginterferon alfa combined
with ribavirin,[14] however this only clears the virus for 40-50 percent of genotype-1
chronic HCV patients.[14,15]

About Janssen

At Janssen, we are dedicated to addressing and solving some of the most important
unmet medical needs of our time in oncology, immunology, neuroscience, infectious diseases
and vaccines, and cardiovascular and metabolic diseases. Driven by our commitment to
patients, we bring innovative products, services and solutions to people throughout the
world.

More information can be found at http://www.janssen-emea.com.

References:

        1) Sulkowski, M S et al.Ribavirin dose modification in treatment-naive and
          previously treated ppatients who received telaprevir combination treatment: no impact
          on sustained virologic response in phase 3 studies. Poster presented at the 47th
          Annual Meeting of the European Association of Study of the Liver (EASL)2012
        2) Copegus(R) Summary of Product Characteristics, updated 2012
        3) Jacobson, I et al. Telaprevir for Previously Untreated Hepatitis C Virus
          Infection. N Engl J Med. 2011;364:2405-16. (ADVANCE)
        4) Sherman, K et al. Response-Guided Telaprevir Combination Treatment for
          Hepatitis C Virus Infection. N Engl J Med. 2011;365:1014-24. (ILLUMINATE)
        5) Zeuzem,S et al. Telaprevir for Retreatment of HCV Infection. N Engl J Med.
          2011;364:2417-28.(REALIZE)
        6) Incivo(R) Summary of Product Characteristics, updated 2011
        7) Curtis S, Cure S, Gavart S, et al. The cost-effectiveness of telaprevir (TVR)
          in combination with pegylated interferon-alfa and ribavirin (PR) for the treatment of
          genotype 1 chronic hepatitis c patients. Paper presented at the 47th Annual Meeting of
          the European Association of Study of the Liver (EASL); 2012
        8) Simin, M et al. Cochrane systematic review: pegylated interferon plus
          ribavirin vs. interferon plus ribavirin for chronic hepatitis C. Alimentary
          Pharmacology & Therapeutics. 2007; 25(10):1153-62.
        9) Centres for Disease Control and Prevention. Hepatitis C FAQs. [cited 2009 Dec
          17] Available from: http://www.cdc.gov/hepatitis/C/cFAQ.htm#transmission.
          10) European Association for the Study of the Liver. EASL Clinical Practice
          Guidelines: Management of hepatitis C virus infection. Journal of Hepatology. 2011;
          55: 245-264
          11) WHO. State of the art of vaccine research and development. Viral Cancers.
          Available from http://www.who.int/vaccine_research/documents/Viral_Cancers.pdf).
          12) Muehlberger, N et al. HCV-related burden of disease in Europe: a systematic
          assessment of incidence, prevalence, morbidity, and mortality. BMC Public Health.
          2009; 9(34):1-14.
          13) Lang K, Weiner DB. Immunotherapy for HCV infection: next steps. Expert
          Review of Vaccines 2008;7(7): 915-923.
          14) McHutchison, J et al. Peginterferon Alfa-2b or Alfa-2a with Ribavirin for
          Treatment of Hepatitis C Infection. N Engl J Med. 2009; 361:580-93.
          15) The Hepatitis C Trust. Treatments: Potential New Drugs. [cited 2010 Feb 20]
          Available from:

http://www.hepctrust.org.uk/treatment/potential-new-drugs/Drugs+that+target+the+virus

          .

SOURCE Janssen Pharmaceutica N.V


Source: PR Newswire