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

Beerse, Belgium (ots/PRNewswire) -

- OPTIMIZE study results presented at EASL show similar sustained
virological response (SVR12) rates in patients with fibrosis or
cirrhosis receiving an

INCIVO(R)(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(R)
(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(R) (telaprevir) 1125 mg combination treatment was similar to
an every eight hours (q8h) regimen of INCIVO(R) (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 48th annual meeting of the European Association for the Study of
the Liver (EASL) in Amsterdam
(http://www.easl.eu/_the-international-liver-congress [http://www.ea
sl.eu/_the-international-liver-congress/general-information ]).
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<25 IU/mL, 12 weeks after last planned 
dose of PR

                              Fibrosis            

  Telaprevir             F0-2          F3-4        Cirrhosis   w/o 
Cirrhosis
    dosing              n=529         n=210          n=103         
n=636

Telaprevir 1125 mg       80%           60%            54%           
78%
 twice daily + PR     (213/267)     (61/102)        (29/54)      
(245/315)

Telaprevir 750 mg        79%           57%            49%           
77%
every 8 hours + PR    (208/262)     (62/108)        (24/49)      
(246/321)

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 (less than or equal
to10g/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(R) (telaprevir)
1125 mg or dosing every 8 hours (q8h) of INCIVO(R) (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(R) (telaprevir)

INCIVO(R) (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(R) 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(R) was approved by the European Commission on the 19th
September 2011. The current approved dose for INCIVO(R) is 750 mg
every 8 hours in combination with PR.

INCIVO(R) 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(R).

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 greater than or equal to 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 greater than or
equal to 1.0%)of at least Grade 3 were anemia, rash,
thrombocytopenia, lymphopenia, pruritus, and nausea. INCIVO(R)
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(R) 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.

MEDIA CONTACT:

Ronan Collins
+44(0)7876-257-746

Ines Hammer
+33(6)8809-33-35

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