Janssen Infectious Diseases-Diagnostics BVBA

INCIVO® (telaprevir) Receives European Commission Approval for Twice Daily Dosing for Treatment of Genotype-1 Chronic Hepatitis C Virus (HCV)

Beerse, Belgium (ots/PRNewswire) - -INCIVO(R) triple therapy now offers a twice daily HCV treatment regimen

which should improve patient adherence[1] -

Janssen Infectious Diseases-Diagnostics BVBA (Janssen) announced today that the European Commission (EC) has approved a new twice daily (BID) dosing of INCIVO(R) (telaprevir), a direct acting antiviral (DAA) protease inhibitor, in combination with pegylated-interferon and ribavirin (PR) for naive and previous treatment experienced patients. The newly approved dosing regimen for INCIVO(R) is now 1,125 mg twice daily in combination with PR, which aligns a morning and evening dose to the already twice daily dosing schedule for ribavirin versus 750 mg every 8 hours in combination with PR.

The EC approval is based on results from OPTIMIZE, a randomized, open-label, multicenter Phase III study in treatment naive patients with genotype-1 chronic HCV infection, which demonstrated that twice daily dosing of INCIVO(R) 1,125mg in combination with PR was non-inferior to the previously approved dosing every 8 hours in the proportion of patients who achieved sustained virologic response (74% versus 73%).[2] Twice daily dosing also showed similar cure rates with twice daily or every 8 hours INCIVO dosing in patients with cirrhosis.[3]

"The approval of INCIVO(R) twice daily is good news for patients with genotype-1 chronic HCV infection. Making treatments more simple and easier to manage, without compromising efficacy, will help to increase adherence and give patients an even greater chance of achieving a cure," said Dr Maria Buti, Hospital Valle Hebron and Ciberehd del Institut Carlos III, Barcelona, Spain.

The availability of new DAAs like telaprevir has transformed treatment options for HCV.[4] Telaprevir has already played a significant role in improving treatment outcomes with more than 80,000 patients treated with telaprevir combination therapy worldwide since it was first approved in 2011.[5] It also offers the shortest total treatment duration of any available HCV therapy, for a high proportion of treatment-naive or relapse patients.[6],[7]

"Before the availability of direct acting antivirals like telaprevir, the best clinicians could hope for was to cure only 40-50% of our genotype-1 HCV patients. DAAs now offer us the chance to cure approaching 80% of these patients, for many in a shorter amount of time. Successful treatment is effectively a cure and causes a massive reduction in the complications of HCV, such as liver cancer and cirrhosis. As with many diseases early therapy is most effective and has the greatest impact on complications. The twice daily dosing of telaprevir makes the treatment easier to administer and will make it easier for patients to take advantage of the opportunity for a cure. We now need to ensure that patients with HCV are identified and offered therapy, before their disease progresses," said Graham Foster, Consultant Hepatologist, Barts Health London.

"We are pleased by the European Commission approval of twice daily dosing for telaprevir, which marks an improvement on an already important treatment option for HCV. This medicine is the cornerstone of our efforts to improve the lives of more people living with HCV and supporting healthcare professionals around the world," said Gaston Picchio, Hepatitis Disease Area Leader at Janssen.

Telaprevir was first approved by the U.S. Food and Drug Administration (FDA) in May 2011, marketed by Vertex Pharmaceuticals under the brand name INCIVEK[TM], and by the European Commission in September 2011, marketed by Janssen Pharmaceutical Companies under the brand name INCIVO(R).

About OPTIMIZE

740 naive patients chronically infected with genotype-1 HCV were treated with either a twice daily dosing of INCIVO 1,125 mg or dosing every 8 hours of INCIVO 750 mg, each in combination with PR. At Week 12, telaprevir treatment ended and patients continued on PR alone for an additional 12 or 36 weeks depending on their viral response at Week 4. Patients were evaluated 12 weeks after treatment ended (SVR12) to monitor sustained virological response (SVR) rates.[2]

The SVR12 rate for the twice daily group was 74% (274/369) compared to 73% (270/371) in the every 8 hour group with 95% confidence interval of the difference: -4.9%, 12.0%. The lower limit of the 95% CI (-4.9%) was greater than the pre-determined non-inferiority margin of -11% and therefore the non-inferiority of twice daily group over every 8 hour group was demonstrated.[7]

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.[7] 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.

INCIVO, 1,125 mg (three 375 mg film-coated tablets) should be taken orally twice daily (BID) with food. Alternatively, 750 mg (two 375 mg tablets) can be taken orally every 8 hours (q8h) with food. The total daily dose is 6 tablets (2,250 mg).[7]

Telaprevir 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 3,441 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.[7] INCIVO(R) prescribing information includes special warnings and pre-cautions for use with regards to rash including Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) and Stevens - Johnson syndrome (SJS)/Toxic Epidermal Necrolysis (TEN), where INCIVO, peginterferon alfa and ribavirin should be immediately and permanently discontinued and a specialist in dermatology consulted.[7] In cases of mild and moderate rash discontinuation of INCIVO(R) is not always required and patients are advised to consult with a healthcare professional. In cases of severe rash immediate discontinuation of INCIVO(R) is required and consultation with a specialist in dermatology is recommended.[7]

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 patientsand 2.6% of patients discontinued telaprevir combination treatment for rash events compared to none of those receiving peginterferon alfa and ribavirin.[7]

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 INCIVO combination treatment due to anemia compared to 0.5% receiving peginterferon alfa and ribavirin.[7]

About HCV

Hepatitis C (HCV) is a contagious liver disease which is spread through blood-to-blood contact and is usually symptomless at the outset.[8] With an estimated 150 million people infected worldwide,[9] and three to four million people newly infected each year, HCV puts a significant burden on patients and society.[10] Estimations indicate that HCV kills more than 350,000 people worldwide per year, accounting for approximately 1% of deaths worldwide.[9] It is the world's primary cause of cirrhosis and liver cancer[11] with an estimated 20-30% of patients developing liver cirrhosis[12] and a further 7% developing liver cancer.[13] The estimated annual cost of HCV (medical and work loss) is more than $1 billion in the U.S. alone.[14]

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. Please visit http://www.janssenrnd.com for more information.

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References:

1) Sievert W et al. Adherence with Telaprevir BID vs. Q8h Dosing in
  Treatment Naive HCV-infected Patients: Results from the Phase III OPTIMIZE Study. J
  Hepatol 2013; 58(Suppl 1): S373.
2) 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. (Final ID: LB-8).
3) 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) Abstract 862.
4) Casey L C, Lee W M. Hepatitis C Virus Therapy Update 2013. Curr Opin
  Gastroenterol. 2013;29(3):243-249.
5) Janssen data on file.
6) Sherman K, et al. Duration of Initial Telaprevir Treatment for HCV Infection:
  A phase 3 study of treatment duration. N Engl J Med. 2011;365:1014-24.
7) INCIVO(R) Summary of Product Characteristics updated 2013.
8) Centers for Disease Control and Prevention. Hepatitis C FAQs. Available at:
  http://www.cdc.gov/hepatitis/C/cFAQ.htm#transmission (last accessed May 2013).
9) World Health Organization. Hepatitis C Fact Sheet. Available at:
  http://www.who.int/mediacentre/factsheets/fs164/en/index.html (last accessed May
  2013).
  10) 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 May 2013).
  11) Rosen HR. Clinical practice. Chronic hepatitis C infection. N Engl J Med.
  2011 Jun 23;364(25):2429-38.
  12) Hep C Trust: Overview of Stages. Available at:
  http://www.hepctrust.org.uk/Hepatitis_C_Info/Stages+of+Hepatitis+C/Overview+of+the+stages
  (last accessed May 2013). 
  13) Blachier M, Leleu H, Peck-Radosavljevic M, et al. The Burden of liver
  disease in Europe: A review of available epidemiological data. European Association
  for the Study of the Liver 2013.
  14) El Khoury A, Klimack W, Wallace C, et al. Economic burden of hepatitis
  C-associated diseases in the United States. J Viral Hep. 2012 March;19:153-160
 

Contact:

MEDIA Ronan Collins, +44(0)7876-257-746, Ines Hammer,
+33(6)8809-33-35



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