INCIVO® Receives Positive Opinion from the Committee for Medicinal Products for Human Use (CHMP) for Twice Daily Dosing for

 INCIVO® Receives Positive Opinion from the Committee for Medicinal Products
   for Human Use (CHMP) for Twice Daily Dosing for Treatment of Genotype-1
                              Hepatitis C Virus

  PR Newswire

  BEERSE, Belgium, April 26, 2013

BEERSE, Belgium, April 26, 2013 /PRNewswire/ --

- OPTIMIZE study results presented at EASL show similar sustained virological
  response (SVR12) rates in patients with fibrosis or cirrhosis receiving an
 INCIVO ^® (telaprevir) combination treatment twice daily versus every eight
                                  hours  -

Janssen Infectious Diseases-Diagnostics BVBA (Janssen), announced today that
the Committee for Medicinal Products for Human Use (CHMP) of the European
Medicines Agency (EMA) adopted a positive opinion recommending the approval of
twice daily (BID) dosing of INCIVO ^® (telaprevir), a direct acting antiviral
(DAA) for the treatment of chronic genotype-1 hepatitis C virus (HCV), in
combination with pegylated-interferon and ribavirin (PR). 

The CHMP positive opinion is a critical step in the approval process and will
be considered by the European Commission, which has authority to approve
medicines for use throughout the European Union. The current approved dose for
INCIVO is 750 mg every 8 hours in combination with PR.

"This positive opinion from the CHMP is an important development for a more
convenient treatment regimen for patients which should help lead to greater
adherence, a critical factor in HCV treatment," said Gaston Picchio, Hepatitis
Disease Area Leader at Janssen R&D. "Telaprevir has already played a huge part
in improving treatment outcomes for people living with hepatitis C with more
than 80,000 people treated to date globally with telaprevir combination
treatment. This recommendation is the next step in our commitment to improving
the lives of more people living with hepatitis C and supporting healthcare
professionals around the world."

Janssen presented clinical trial results showing that the relative efficacy of
a twice daily (BID) investigational dosing regimen of INCIVO® (telaprevir)
1125 mg combination treatment was similar to an every eight hours (q8h)
regimen of INCIVO® (telaprevir) 750 mg combination treatment in HCV genotype-1
patients regardless of fibrosis or cirrhosis based on sustained virological
response rates at 12 weeks after the last treatment dose (SVR12). ^[1] These
results, a sub-analysis from the OPTIMIZE Phase 3 trial, were presented
during the 48 ^th annual meeting of the European Association for the Study of
the Liver (EASL) in Amsterdam (
http://www.easl.eu/_the-international-liver-congress ). Additional
sub-analyses from this study evaluating anemia management, ^[2] efficacy in
patients by the IL28B genotype ^[3] and patient adherence ^[4] were also
presented.

"Simplifying available treatment regimens for HCV, without compromising on
cure rates is especially important for patients with fibrosis or cirrhosis. We
know that telaprevir combination treatment offers patients improved cure rates
over treatment with pegylated interferon and ribavirin alone. These results
confirm that a twice daily dosing schedule for a telaprevir-based regimen
gives patients a similar chance of achieving SVR12 as the current approved
dose in a population who desperately need more effective treatment," said Yves
Horsmans, Lead Study Investigator and Professor at Cliniques Universitaires
Saint-Luc, Belgium.

Results from the sub-analysis of the 740 patients included in the OPTIMIZE
study showed that those with cirrhosis who received a twice daily dose of
telaprevir 1125 mg in combination with PR, achieved similar SVR12 rates
compared with those who received telaprevir 750 mg every 8 hours in
combination with PR (54% versus 49%). ^[1] Patients at other stages of
fibrosis, F0 to F4, also achieved similar SVR12 rates with a twice daily dose
of telaprevir 1125 mg in combination with PR compared with those who received
telaprevir 750 mg every 8 hours in combination with PR (see table 1). 

    Table 1: SVR 12 rates, HCV RNA

The safety and tolerability of telaprevir across fibrosis or cirrhosis stages
were consistent with previous studies. ^[1] Grade 3 or 4 adverse events (AEs)
were reported in 41% of patients with and 40% of patients without cirrhosis.
^[1] Serious adverse events and discontinuations due to adverse events were
higher in patients with cirrhosis than those without (14% and 21% versus 8%
and 16%, respectively). ^[1] The most common adverse events experienced were
fatigue, pruritus, anemia, nausea and rash. ^[5] The proportion of patients
who experienced a low haemoglobin level (≤10g/dL) was higher among patients
with (50%) than without cirrhosis (42%). ^[1]

Results from an additional sub-analysis of the OPTIMIZE study found that
adherence was greater in patients who received twice daily dosing of
telaprevir compared to every eight hours. ^[4] "Treating HCV can be complex
and therefore anything that can help make effective treatments simpler and
adherence easier for patients will ultimately improve their chance of
achieving a cure," said study investigator Dr Maria Buti, Hospital Val
d'Hebron, Spain.

Additional telaprevir data from the OPTIMIZE study presented at EASL
includes*:

  *Anemia and its management in patients treated with telaprevir twice daily
    ^[2]
  *Efficacy of telaprevir dosed twice daily versus every 8 hours by IL28B
    genotype ^[3]
  *Adherence with telaprevir BID vs q8h dosing in treatment-naïve
    HCV-infected patients ^[4] *  Poster session: Friday , April 26 from 9:00
    AM-6:00 PM

Additional telaprevir data presented at EASL includes*:

  *Management and outcomes of anemia in the International Telaprevir Early
    Access Program, for patients with hepatitis C genotype 1 infection ^[6]
  *Treatment with telaprevir-based therapy after exposure to peg-IFN/RBV in
    the REALIZE study ^[7]
  *Treatment with telaprevir/peg-IFN/RBV after 14-day telaprevir exposure in
    Phase I studies ^[8]
  *High SVR rates (SVR4) for 12‐week total telaprevir combination therapy in
    IL28B CC treatment‐naïves and prior relapsers with G1 chronic hepatitis C:
    CONCISE interim analysis ^[9] *  Poster session: Friday , April 26 from
    9:00 AM-6:00 PM

About OPTIMIZE

OPTIMIZE is a randomized, open-label, multicenter Phase 3 study in patients
with genotype-1 chronic HCV infection who have not been previously treated.
During the study, 740 patients were randomized to receive either a twice daily
(BID) dosing of INCIVO ^® (telaprevir) 1125 mg or dosing every 8 hours (q8h)
of INCIVO ^® (telaprevir) 750 mg, each in combination with PR. At 12 weeks,
telaprevir treatment ended and patients continued on PR alone for up to week
24 or week 48 depending on their viral response at week 4. Patients were
followed up for a further 12 weeks to monitor SVR rates (SVR12). ^[5]

About INCIVO® (telaprevir)

INCIVO ^® (telaprevir), in combination with peginterferon alfa and ribavirin
(PR), is indicated for the treatment of genotype-1 chronic HCV in adult
patients with compensated liver disease (including cirrhosis) who are
treatment-naïve, 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. ^[10] 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 the 19 ^th September 2011. The current approved
dose for INCIVO ^® is 750 mg every 8 hours in combination with PR.

INCIVO ^® was developed by Janssen Infectious Diseases-Diagnostics BVBA, one
of the Janssen Pharmaceutical Companies, in collaboration with Vertex
Pharmaceuticals Incorporated (Vertex) and Mitsubishi Tanabe Pharma Corporation
(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 ^® .

Important Safety Information

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

The overall safety profile of telaprevir is based on the Phase II/III clinical
development programme containing 2,641 patients who received a telaprevir
based regimen. 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 adverse reactions (incidence ≥ 5.0%) of at least grade 2
in severity were anemia, rash, pruritus, nausea, and diarrhoea during the
telaprevir treatment phase, and the most frequently reported adverse reactions
(incidence ≥ 1.0%)of at least Grade 3 were anemia, rash, thrombocytopenia,
lymphopenia, pruritus, and nausea. INCIVO ^® prescribing information includes
special warnings and pre-cautions for use with regards to severe rash
including Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) and
Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN). ^[10]

Rash events were reported in 55% of patients with a telaprevir based regimen
compared to 33% of patients treated with peginterferon alfa and ribavirin only
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 of telaprevir alone in 5.8% of patients and 2.6% of
patients discontinued telaprevir combination treatment for rash events
compared to none of those receiving peginterferon alfa and ribavirin. ^[10] 

Hemoglobin values of < 10 g/dl were observed in 34% of patients who received
telaprevir combination treatment and in 14% of patients who received
peginterferon alfa and ribavirin. In placebo-controlled Phase 2 and 3 trials,
1.9% of patients discontinued telaprevir alone due to anemia, and 0.9% of
patients discontinued telaprevir combination treatment due to anemia compared
to 0.5% receiving peginterferon alfa and ribavirin. ^[10] 

About HCV

Hepatitis C (HCV) is a blood-borne infectious disease that spreads through
blood-to-blood contact, damages the liver and may impair a person's life.
^[11] While it is usually symptomless at the outset - it is the world's
primary cause of cirrhosis and liver cancer. ^[12] With an estimated 150
million people infected worldwide, ^[13] and three to four million people
newly infected each year, HCV puts a significant burden on patients and
society. ^[14] 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 (latest data available). ^[15] Chronic infection with HCV About
one-quarter of the liver transplantations performed in 25 European countries
in 2004 were attributable to HCV (latest data available). ^[15] 

About Janssen

At Janssen, we are dedicated to addressing and solving some of the most
important unmet medical needs of our time in infectious diseases and vaccines,
oncology, immunology, neuroscience, and cardiovascular and metabolic diseases.
Driven by our commitment to patients, we develop innovative products, services
and healthcare solutions to help people throughout the world. Janssen
Infectious Diseases-Diagnostics BVBA is part of the Janssen Pharmaceutical
Companies of Johnson & Johnson. Please visit http://www.janssenrnd.com for
more information.

References:

1.Horsmans Y, Brown Jr. RS, Buti M et al. Safety and efficacy of twice daily
    versus every 8 hour telaprevir with peginterferon/ribavirin (PR) in
    patients with cirrhosis. 2013. European Association for the Study of the
    Liver (EASL) Poster 985.
2.Zeuzem S, Buti M, Agarwal K et al. Anemia and its management in patients
    treated with telaprevir twice-daily versus every 8 hours in the Phase III
    OPTIMIZE study. 2013. European Association for the Study of the Liver
    (EASL) Abstract 919.
3.Buti M, Agarwal K, Horsmans Y. Efficacy of telaprevir dosed twice daily
    versus every 8 hours by IL28B genotype: results from the Phase III
    OPTIMIZE study. 2013. European Association for the Study of the Liver
    (EASL) Abstract 798.
4.Sievert W, Buti M, Agarwal K. Adherence with telaprevir BID vs q8h dosing
    in treatment-naïve HCV-infected patients: results from the Phase III
    OPTIMIZE study. 2013. European Association for the Study of the Liver
    (EASL) Abstract 905.
5.Buti M, Agarwal K, Horsmans Y, et al. OPTIMIZE Trial: Non-inferiority of
    twice-daily telaprevir versus administration of every 8 hours in
    treatment-naïve, genotype 1 HCV infected patients. 2012. American
    Association for the Study of Liver Diseases (AASLD) Abstract LB-8
6.Colombo M, Fernández I, Abdurakhmanov D. Management and outcomes of
    anaemia in the International telaprevir Early Access Program, for patients
    with hepatitis C genotype 1 infection. 2013. European Association for the
    Study of the Liver (EASL) Abstract 806.
7.Mathurin P, Sarrazin C, Reesink HW. Treatment with telaprevir-based
    therapy after exposure to PEG-IFN/RBV in the REALIZE study: results from
    the Phase IIIB C219 rollover study. 2013. European Association for the
    Study of the Liver (EASL) Abstract 868.
8.Sarrazin C, Reesink HW, Zeuzem S. Treatment with telaprevir/PEG-IFN/RBV
    after 14-day telaprevir exposure in Phase I studies: results from the
    Phase IIIB C219 rollover study. 2013. European Association for the Study
    of the Liver (EASL) Abstract 898.
9.Nelson DR, Poordad F, Feld JJ, et al. High SVR rates (SVR4) for 12‐week
    total telaprevir combination therapy in IL28B CC treatment‐naïves and
    prior relapsers with G1 chronic hepatitis C: CONCISE interim analysis.
    2013. European Association for the Study of the Liver (EASL) Abstract.
10.INCIVO® Summary of Product Characteristics, updated 2013.
11.Centres for Disease Control and Prevention. Hepatitis C FAQs. Available
    at: http://www.cdc.gov/hepatitis/C/cFAQ.htm#transmission (last accessed
    March 2013).
12.Rosen, HR. Clinical practice. Chronic hepatitis C infection. N Engl J Med.
    2011 Jun 23;364(25):2429-38.
13.World Health Organization. Hepatitis C Fact Sheet. Available at:
    http://www.who.int/mediacentre/factsheets/fs164/en/index.html (last
    accessed March 2013).
14.WHO. State of the art of vaccine research and development. Viral Cancers.
    Available at:
    http://www.who.int/vaccine_research/documents/Viral_Cancers.pdf (last
    accessed March 2013).
15.Mühlberger, 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.

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