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

Barcelona, Spain (ots/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
.

ots Originaltext: Janssen Pharmaceutica N.V
Im Internet recherchierbar: http://www.presseportal.de

Contact:
MEDIA Daniel De Schryver, +49-173-7689-149