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Last updated on April 17, 2014 at 21:23 EDT

INCIVO(R) 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

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(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.easl.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-naive 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   naives 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-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.[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-naive 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-naive,
          genotype 1 HCV infected patients. 2012. American Association for the Study of Liver
          Diseases (AASLD) Abstract LB-8
        6) Colombo M, Fernandez 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   naives 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) Muhlberger, 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

SOURCE Janssen


Source: PR Newswire