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

PR Newswire

BEERSE, Belgium, May 31, 2013 /PRNewswire/ --

-INCIVO® 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® (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® 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® 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® 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-naïve 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®.

About OPTIMIZE

740 naïve 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® (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.^[7] 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^thSeptember 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®.

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 ≥ 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.^[7] INCIVO® 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® is not always required and patients are advised to consult with a healthcare professional. In cases of severe rash immediate discontinuation of INCIVO® 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.

###

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-naïve, 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® 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

Source

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

July 22, 2011

-Expanding new treatment class for patients with HCV-

Beerse, Belgium, 22 July, 2011 - Tibotec Virco-Virology BVBA, one of the Janssen Pharmaceutical Companies, 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 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, the previously accepted standard of care.

The CHMP positive opinion is based on results from three phase III clinical trials, ADVANCE¹, REALIZE² and ILLUMINATE³ which evaluated the efficacy and safety of telaprevir in combination with pegylated-interferon and ribavirin in more than 2,290 treatment-naïve and previously-treated genotype 1 HCV patients.^1,2,3 Data from ADVANCE and REALIZE were published in the 23^rd June edition of the New England Journal of Medicine. Data from the ILLUMINATE study were presented at the 61^st annual meeting of the American Association for the Study of Liver Diseases in 2010.

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. Telaprevir was approved by the U.S. Food and Drug Administration (FDA) in May 2011 and is marketed by Vertex Pharmaceuticals under the brand name INCIVEK^™. Following marketing authorization approvals, telaprevir will be marketed in the EU and certain other global territories under the brand name INCIVO by the Janssen Companies.

"We are encouraged by this positive decision from the CHMP and will continue to work closely with other regulatory authorities to make telaprevir available for people with HCV. If approved by the European Commission, the addition of telaprevir will offer patients an improved treatment option compared to the previously accepted standard of care, which only cures 40-50 percent of genotype 1 patients" said Ramon Polo, INCIVO Compound Development Team Leader. "Telaprevir is part of Janssen's expanding infectious disease portfolio, which is comprised of innovative therapies in HIV/AIDS, tuberculosis and now HCV that are helping to redefine and improve treatment outcomes. Janssen remains dedicated to improving the lives of patients and supporting healthcare professionals around the world."

About INCIVO
INCIVO is being developed by Tibotec, one of the Janssen Pharmaceutical Companies, in collaboration with Vertex Pharmaceuticals and Mitsubishi Tanabe Pharma. The Janssen Companies have the right to commercialize telaprevir in Europe, Latin America, the Middle East, Africa, India, Australia and New Zealand under the commercial name INCIVO^®; Vertex has the right to commercialize telaprevir in North America under the name INCIVEK^™; Mitsubishi Tanabe Pharma has the right to commercialize telaprevir in Japan and certain Far Eastern countries.

On May 23^rd 2011, US FDA approved telaprevir for the treatment of people with chronic genotype 1 hepatitis C with compensated liver disease.

About HCV
HCV is a blood-borne infectious disease that affects the liver.⁴ With an estimated 170 million people infected worldwide, and three to four million people newly infected each year,⁵ HCV puts a significant burden on patients and society. Chronic infection with HCV can lead to liver cancer and other serious and fatal liver diseases, and is the most common cause of liver transplant in Europe.⁶ The previously accepted standard of treatment for HCV is pegylated-interferon combined with ribavirin,⁷ however this only cures 40-50 percent of genotype 1 patients.⁸

About Tibotec
Tibotec Virco-Virology BVBA, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, is a global pharmaceutical and research development company. The Company's main research and development facilities are in Beerse, Belgium with offices in Titusville, NJ and Cork, Ireland. Tibotec is dedicated to the discovery and development of innovative HIV/AIDS and hepatitis C drugs, and anti-infectives for diseases of high unmet medical need.

About Janssen
The Janssen Pharmaceutical Companies of Johnson & Johnson are dedicated to addressing and solving the most important unmet medical needs of our time, including oncology , immunology, neuroscience, infectious disease, 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.

More information can be found at www.janssen-emea.com

This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Tibotec Virco-Virology BVBA, any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to, general industry conditions and competition; economic factors, such as interest rate and currency exchange rate fluctuations; technological advances and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; domestic and foreign health care reforms and governmental laws and regulations; trends toward health care cost containment; and increased scrutiny of the healthcare industry by government agencies. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 2, 2011. Copies of this Form 10-K, as well as subsequent filings, are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. The Janssen Pharmaceutical Companies and Johnson & Johnson do not undertake to update any forward-looking statements as a result of new information or future events or developments.

References:

1. John G et al. Telaprevir in Combination with Peginterferon and Ribavirin in Genotype 1 HCV Treatment-Naïve Patients: Final Results of Phase 3 ADVANCE study. Paper presented at: The Liver Meeting of the American Association for the Study of Liver Diseases (AASLD); 2010.
2. Zeuzem S, Andreone P, Pol S et al. REALIZE trial final results: telaprevir-based regimen for genotype 1 hepatitis C virus infection in patients with prior null response, partial response or relapse to peginterferon/ribavirin. Paper presented at: 46th annual meeting of the European Association for the Study of the Liver (EASL); 2011.
3. Sherman KE et al. Telaprevir in Combination with Peginterferon Alfa2a and Ribavirin for 24 or 48 weeks in Treatment-Naive Genotype 1 HCV Patients who Achieved an Extended Rapid Viral Response: Final Results of Phase 3 ILLUMINATE Study. Paper presented at: The Liver Meeting of the American Association for the Study of Liver Diseases (AASLD); 2010.
4. Centres for Disease Control and Prevention. Hepatitis C FAQs. [cited 2009 Dec 17] Available from: http://www.cdc.gov/hepatitis/C/cFAQ.htm#transmission.
5. World Health Organization. Hepatitis C. Weekly Epidemiological Record. 1997;72:65-69.
6. 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.
7. 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.
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.

Source

Twice-daily INCIVO® (Telaprevir), in Combination With Peginterferon Alfa and Ribavirin, is Effective in Treating People Living With Genotype-1 Chronic Hepatitis C Virus

By Janssen Pharmaceutical

BEERSE, Belgium, October 16, 2012 -- /PRNewswire/ --

NOT INTENDED FOR US JOURNALISTS

- OPTIMIZE study results to be presented in late-breaking poster presentation at the American Association for the Study of Liver Diseases (AASLD) 2012 show non-inferior sustained virological response (SVR12) rates in previously untreated genotype-1 patients receiving an INCIVO® (telaprevir) based regimen twice-daily versus every eight hours -

Janssen Research & Development Infectious Diseases - Diagnostics BVBA (Janssen) will present results from the OPTIMIZE Phase 3 trial for INCIVO® (telaprevir), during a late-breaking poster presentation at the 63rd annual meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston (http://www.aasld.org/lm2012). The study, which was completed in September, investigates the efficacy and safety of the twice-daily dosing (BID) of telaprevir versus dosing every eight hours (q8h) in people chronically infected with genotype-1 hepatitis C virus (HCV) who had not been previously treated.^[1]

"This is the first Phase 3 study to evaluate twice daily dosing of the new class of protease inhibitors for the treatment of hepatitis C, so this will be significant news for patients and clinicians," said Maria Buti, Lead Study Investigator and Professor of Medicine at Hospital General Universitari VAll d'Hebron, Barcelona. "Telaprevir has already halved the treatment duration for the majority of people with hepatitis C whilst significantly improving cure rates, compared to previous standard of care, peginterferon alfa and ribavirin (PR). These data offers hope for yet further improvements to treatment regimens, with no compromise on cure rates."

The results demonstrated that BID dosing of telaprevir 1,125mg in combination with peginterferon alfa and ribavirin (PR), achieved similar cure rates, also known as sustained virological response (SVR12) to q8h dosing of telaprevir 750mg (74.3% versus 72.8%), thereby meeting its primary objective of non-inferiority versus q8h dosing.^[1] The safety and tolerability of telaprevir was comparable across dosing arms and consistent with previous studies. The most common adverse events experienced were fatigue, pruritus, anemia, nausea and rash.^[1]

OPTIMIZE was a randomized, open-label, multicenter Phase 3 study in patients with genotype-1 chronic HCV infection who had not been previously treated. During the study, 744 patients were randomized to either BID dosing of telaprevir 1,125mg or q8h dosing of telaprevir 750mg (current INCIVO® label), 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 cure rates (SVR12).^[1]

Additional telaprevir data to be presented at AASLD will include:

- Efficacy and safety of telaprevir in patients co-infected with HCV and HIV^[2]

- Interim analysis results from the telaprevir Global Early Access Programme highlighting the efficacy and safety of treatment amongst genotype-1 HCV patients with severe fibrosis or compensated cirrhosis^[3]

- Factors predictive of anemia development in treatment-experienced patients receiving telaprevir plus PR in the REALIZE trial^[4]

- Rate of disappearance of telaprevir resistant variants using clonal and population sequence data from Phase 3 studies^[5]

- Evaluation of liver and plasma HCV RNA kinetics and telaprevir levels in genotype-1 HCV patients treated with telaprevir (TVR) using serial fine needle aspirates (FNA)^[6]

- Deep sequencing of the HCV NS3/4A region confirms low prevalence of telaprevir-resistant variants both at baseline and end of study^[7]

About INCIVO®

INCIVO® (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 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.^[8] 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 Research & Development 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 2/3 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.^[8]

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.^[8]

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.^[8]

About HCV

HCV is a blood-borne infectious disease that affects the liver.^[9],[10] With an estimated 130-210 million people infected worldwide,^[11]and three to four million people newly infected each year, HCV puts a significant burden on patients and society.^[12] 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 available data).^[13] Chronic infection with HCV can lead to liver cancer and other serious and fatal liver diseases.^[14] About one-quarter of the liver transplants performed in 25 European countries in 2004 were attributable to HCV (latest available data).^[13] The previously accepted standard treatment for HCV was peginterferon alfa combined with ribavirin,^[14] however this only cleared the virus for 40-50 percent of genotype-1 chronic HCV patients.^[15],[16]

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 develop innovative products, services and healthcare solutions to help people throughout the world. Janssen Research & Development Infectious Diseases - Diagnostics BVBA is part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Please visit http://www.janssenrnd.com for more information.

1. 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.

2. Sulkowski MS, Sherman KE, Soriano V , et al. Telaprevir in Combination with Peginterferon Alfa-2a/Ribavirin in HCV/HIV Co-infected Patients: SVR24 Final Study Results. 2012. American Association for the Study of Liver Diseases (AASLD) Abstract.

3. Colombo M et al. Treatment of Hepatitis C Genotype 1 Patients with Severe Fibrosis or Compensated Cirrhosis: The International Telaprevir Early Access Program. 2012. American Association for the Study of Liver Diseases (AASLD) Abstract.

4. Zeuzem S, DeMasi R, Baldini A, et al. Factors predictive of anemia development in treatment-experienced patients receiving telaprevir (T;TVR) plus peginterferon/ribavirin (PR) in the REALIZE trial. 2012. American Association for the Study of Liver Diseases (AASLD) Abstract.

5. Sullivan J, De Meyer S, Haseltine E, et al. Rate of disappearance of telaprevir resistant variants using clonal and population sequence data from Phase 3 studies. 2012. American Association for the Study of Liver Diseases (AASLD) Abstract.

6. Talal A, Dimova R, Zhang E, et al. Evaluation of Liver And Plasma HCV RNA Kinetics And Telaprevir Levels In Genotype 1 HCV Patients Treated With Telaprevir (TVR) Using Serial Fine Needle Aspirates (FNA). 2012. American Association for the Study of Liver Diseases (AASLD) Abstract.

7. Dierynck I, De Meyer S, Thys K, et al. Deep Sequencing of the HCV NS3/4A Region Confirms Low Prevalence of Telaprevir-resistant Variants Both at Baseline and End of Study. 2012. American Association for the Study of Liver Diseases (AASLD) Abstract.

8. Incivo® Summary of Product Characteristics, updated 2011

9. 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.

10. Centres for Disease Control and Prevention. Hepatitis C FAQs. [cited 2009 Dec 17] Available from: http://www.cdc.gov/hepatitis/C/cFAQ.htm#transmission

11. 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.

12. WHO. State of the art of vaccine research and development. Viral Cancers. Available from http://www.who.int/vaccine_research/documents/Viral_Cancers.pdf).

13. 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.

14. Lang K, Weiner DB. Immunotherapy for HCV infection: next steps. Expert Review of Vaccines 2008;7(7): 915-923.

15. 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.

16. 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.

SOURCE Janssen Pharmaceutical

Source

NICE recommends Victrelis and Incivo for hepatitis C

Published: 26/04/2012

Janssen’s Incivo and MSD’s Victrelis have been recommended for reimbursement by the NHS when used in the treatment of hepatitis C.

The National Institute for Health and Clinical Excellence (NICE), which serves as a cost watchdog for England and Wales, has published guidance stating that both treatments should be available for the treatment of genotype 1 chronic hepatitis C, when used in combination with peginterferon alfa and ribavirin.

Professor Carole Longson, health technology evaluationcentre director at NICE, said: “The significant improvement in sustained virological response rates seen with boceprevir or telaprevir plus peginterferon alfa and ribavirin compared with peginterferon alfa and ribavirin alone represents a major benefit for people with genotype 1 chronic hepatitis C.”

Genotype 1 is the most common subtype of hepatitis C in England and Wales affecting around half of the estimated 255,000 people with hepatitis in the region.

It is also the most resistant to treatment, with Longson describing how patients have declined treatment with peginterferon alfa andribavirin alone as the chance for a sustained response was too low to compensate for side effects such as nausea, insomnia, depression and diarrhoea.

Both Incivo and Victrelis work the same way by inhibiting the activity of the NS3/4A serine protease, an enzyme that is essential for viral replication.

NICE said that the serine protease may be partially responsible for the ability of the hepatitis C virus to evade clearance by the host immune system.

The guidance was welcomed by patient group, the Hepatitis C Trust. The organisation’s chief executive Charles Gore said: "People living with genotype-1 hepatitis C who have perhaps been delaying starting treatment, or who have lost hope after their previous treatment had failed them, can now be offered cost effective treatments that offer them a much better chance of clearing the virus than ever before.

“This is really great news and I look forward to direct acting anti-virals being made available to all patients on the NHS as soon as possible."

Source

EASL 2012: INCIVO® (Telaprevir) SVR Rates Unaffected by Ribavirin Dose Reduction in Treatment Naïve and Previously Treated Patients With Genotype-1 Chronic HCV

PRESS RELEASE

April 18, 2012, 11:05 a.m. EDT

BARCELONA, Spain, April 18, 2012 /PRNewswire via COMTEX/ -- 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 = 600mg/day in a telaprevir-based treatment regimen for both treatment naïve 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-naïve 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 = 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 = 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-naïve 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-naïve 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-naïve and experienced patients, regardless of IL28B subtype, according to the threshold of £20,000-£30,000 per quality-adjusted life year (QALY)[7]

About INCIVO®

INCIVO® (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 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.[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®.

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 = 5.0%) were anaemia, rash, pruritus, nausea, and diarrhoea, and the most frequently reported severe adverse reactions (incidence = 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:

Sulkowski, M S et al.Ribavirin dose modification in treatment-naïve 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

Copegus® Summary of Product Characteristics, updated 2012

Jacobson, I et al. Telaprevir for Previously Untreated Hepatitis C Virus Infection. N Engl J Med. 2011;364:2405-16. (ADVANCE)

Sherman, K et al. Response-Guided Telaprevir Combination Treatment for Hepatitis C Virus Infection. N Engl J Med. 2011;365:1014-24. (ILLUMINATE)

Zeuzem,S et al. Telaprevir for Retreatment of HCV Infection. N Engl J Med. 2011;364:2417-28.(REALIZE)

Incivo® Summary of Product Characteristics, updated 2011

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

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.

Centres for Disease Control and Prevention. Hepatitis C FAQs. [cited 2009 Dec 17] Available from: http://www.cdc.gov/hepatitis/C/cFAQ.htm #transmission.

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

WHO. State of the art of vaccine research and development. Viral Cancers. Available from http://www.who.int/vaccine_research/documents/Viral_Cancers.pdf ).

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.

Lang K, Weiner DB. Immunotherapy for HCV infection: next steps. Expert Review of Vaccines 2008;7(7): 915-923.

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.

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.

SOURCE Janssen Pharmaceutica N.V

Source

EASL 2012: INCIVO ® (Telaprevir) in Combination With Peginterferon Alfa and Ribavirin is Cost-effective for Both Treatment-naïve and Experienced Patients With Chronic Genotype-1 Hepatitis C Virus

BEERSE, Belgium, April 4, 2012 /PRNewswire/ --

Not Intended for US Journalists

- Analysis to be presented at European Association for the Study of the Liver (EASL) 2012 shows clinical and cost-effectiveness regardless of IL28B subtype -

Janssen Pharmaceutica NV (Janssen) will present a cost-effectiveness analysis for INCIVO(telaprevir) at the 47th annual meeting of the European Association for the Study of the Liver (EASL) in Barcelona. The analysis demonstrates that the addition of telaprevir to peginterferon alfa and ribavirin (PR) is cost-effective for both treatment-naïve and experienced patients with genotype-1 chronic hepatitis C virus (HCV), regardless of IL28B subtype.1 The analysis considers cost-effectiveness in terms of incremental cost per quality adjusted life year (QALY) gained from the perspective of the NHS in England and Wales.1

The analysis showed that the improved clinical outcomes from the addition of telaprevir to PR for the treatment of genotype-1 chronic HCV infection result in an Incremental Cost Effectiveness Ratio (ICER)1,2 of £13,553 for treatment-naïve patients and an average of £8,688 for treatment-experienced patients.1 The ICER is different depending on the characteristics of treatment-experienced patients, but for all groups, regardless of IL28B subtype, telaprevir was shown to be cost-effective according to the threshold of £20,000-£30,000 per quality adjusted life year (QALY).1,3,which is a measurement of the impact of a treatment on patient quality of life. Health authorities generally view a treatment to be cost-effective if it does not cost more than £20,000-£30,000 per QALY.1,3

Alessandra Baldini, EMEA Medical Affairs Director, Janssen said: "INCIVO has demonstrated a significant improvement in sustained virologic response (SVR) rates for genotype-1 chronic HCV compared to standard treatment with pegylated interferon and ribavirin, including for those patients who were considered difficult to treat. The analysis shows that the clinical benefits and improved outcomes provide a cost-effective long-term benefit for patients with genotype-1 chronic HCV infection."

Data from Phase 3 clinical trials showed that telaprevir in combination with PR demonstrated significant improvements in SVR, compared with PR alone, for both previously untreated genotype-1 chronic HCV patients and those who had failed previous treatment.4,5

"The cost-effectiveness of new direct-acting antivirals for HCV is an important consideration for national health authorities when assessing the benefit of making these treatments available for patients." said Charles Gore, President of the World Hepatitis Alliance. "The availability of direct acting antivirals like telaprevir has been a huge step forward in the fight against chronic HCV infection, giving more patients than ever the hope of clearing the virus from their bodies. We know that the long-term consequences of HCV can be devastating for both patients and health systems, so it is encouraging to see that these treatments are cost-effective in the long term."

An estimated 130-210 million people are infected with HCV worldwide6, and the virus has been described as a 'timebomb' by the World Health Organization due to low diagnosis and treatment rates and long-term consequences of HCV infection such as liver cirrhosis and liver cancer.6 Despite the availability of treatment options, as few as 3.5% of people with HCV are currently receiving treatment in Europe.7

1. Additional telaprevir data to be presented at EASL will include:
2. Retrospective sub-analyses from ADVANCE, ILLUMINATE and REALIZE studies in treatment naïve and previously untreated patients with genotype-1 chronic HCV showing that SVR rates for patients receiving telaprevir in combination with PR were not substantially affected by a ribavirin dose reduction8

About INCIVO®

INCIVO® (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 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.9 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 INCIVEKTM. 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 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 ≥ 5.0%) were anaemia, rash, pruritus, nausea, and diarrhoea, and the most frequently reported severe adverse reactions (incidence ≥ 1.0%) were anaemia, rash, thrombocytopenia, lymphopenia, pruritus, and nausea.9

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%.9

About HCV

HCV is a blood-borne infectious disease that affects the liver.10,11With an estimated 130-210 million people infected worldwide,6 and three to four million people newly infected each year, HCV puts a significant burden on patients and society.12 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 2002.13 Chronic infection with HCV can lead to liver cancer and other serious and fatal liver diseases.14 About one-quarter of the liver transplants performed in 25 European countries in 2004 were attributable to HCV.13 The previously accepted standard treatment for HCV is peginterferon alfa combined with ribavirin,15 however this only clears the virus for 40-50 percent of genotype-1 chronic HCV patients.15,16

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 www.janssen-emea.com.

References:

1. 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. Poster presented at the 47th Annual Meeting of the European Association of Study of the Liver (EASL); 2012
2. Phillips C, What is Cost-effectiveness? Health Economics. Available via URL http://www.medicine.ox.ac.uk/bandolier/painres/download/whatis/Cost-effect.pdf
3. NICE, Measuring effectiveness and cost effectiveness: the QALY. Available via URL: http://www.nice.org.uk/newsroom/features/measuringeffectivenessandcosteffectivenesstheqaly.jsp
4. Zeuzem, S et al. Telaprevir for Retreatment of HCV Infection. N Engl J Med. 2011;364:2417-28.(REALIZE)
5. Jacobson, I et al. Telaprevir for Previously Untreated Hepatitis C Virus Infection. N Engl J Med. 2011;364:2405-16. (ADVANCE)
6. 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
7. Lettmeier B, Mühlberger N, Schwarzer R et al. Market uptake of new antiviral drugs for the treatment of hepatitis C. Journal of Hepatology 2008;49:528-536.
8. Sulkowski, M S et al. Ribavirin dose modification in treatment-naïve and previously treated ppatients who received telaprevir combination treatment: no impact on sustained virologic response in phase 3 studies. Presented at EASL 2012
9. Incivo® Summary of Product Characteristics, updated 2011
10. 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.
11. Centres for Disease Control and Prevention. Hepatitis C FAQs. [cited 2009 Dec 17] Available from: http://www.cdc.gov/hepatitis/C/cFAQ.htm#transmission.
12. WHO. State of the art of vaccine research and development. Viral Cancers. Available from http://www.who.int/vaccine_research/documents/Viral_Cancers.pdf).
13. 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.
14. Lang K, Weiner DB. Immunotherapy for HCV infection: next steps. Expert Review of Vaccines 2008;7(7): 915-923.
15. 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.
16. 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 .

SOURCE Janssen Pharmaceutica NV

Source

NICE final draft "yes" for Incivo

UK News | March 20, 2012

Lynne Taylor

The National Institute for Health and Clinical Excellence (NICE) has issued final draft guidance recommending Janssen Cilag's Incivo (telaprevir), in combination with peginterferon alfa and ribavirin, as an option for the treatment of genotype 1 chronic hepatitis C in adults with compensated liver disease.

The final guidance recommends the drug as an option for the treatment of such patients who are previously untreated or in whom previous treatment with peginteron alfa and ribavirin has failed, including people whose condition has relapsed, partially responded or did not respond.

Commenting on the draft recommendations, Meindert Boysen, programme director for technology appraisals at NICE, pointed out that chronic hepatitis C can have a significant impact on quality of life, particularly if it progresses to the fibrosis and cirrhosis stages.

"Fear of transmitting the disease is also a concern, particularly for women of child-bearing age for whom there is a risk of transmitting the disease to their unborn child,” he added.

NICE says its independent appraisal committee had heard that the current treatment regimen for chronic hepatitis C is often lengthy and that the side effects of treatment themselves can have a significant impact on daily life.

"The significant improvement in sustained virological response rates seen with telaprevir plus peginterferon alfa and ribavirin compared with peginterferon alfa and ribavirin alone, and its potential for shortening the treatment time from the full 48-week course needed for a virological response, therefore represents a major benefit for people with chronic hepatitis C," said Mr Boysen.

NICE is “pleased to be able to recommend teleprevir as a cost-effective use of NHS resources" alongside the final draft guidance also issued this month for Merck Sharp & Dohme's Victrelis (boceprevir), he added.

This latter final draft also recommends Victrelis, in combination with peginterferon alfa and ribavirin, as an option for the treatment of genotype 1 chronic hepatitis C in adults with compensated liver disease.

Graham Foster, professor of hepatology at Barts and the London School of Medicine and Dentistry, welcomed NICE’s positive recommendation for Incivo’s clinical and cost-effectiveness. "We have approved new treatments which significantly increase these patients' chances of clearing the virus and offers some patients a shorter treatment duration. We must now ensure that patients are in a position to access the new antiviral treatments which offer them a very good chance of clearing the virus,” said Prof Foster.

- Figures from 2009 suggest that around 146,000 people were chronically infected with the hepatitis C virus. Genotype 1 is the most common subtype of hepatitis C in England and Wales, affecting 40%-50% of people with hepatitis, and is the most resistant to treatment. Poor diagnosis and compliance rates and a high annual incidence of new infection mean that chronic hepatitis C presents a major public health challenge, despite the availability of treatments that provide the opportunity to address this challenge, says NICE.

Source

NICE Publishes Final Draft Guidance on telaprevir for Chronic Hepatitis C

Healthcare guidance body NICE has today (16 March) issued final draft guidance recommending telaprevir (Incivo, Janssen Cilag), in combination with peginterferon alfa and ribavirin, as an option for the treatment of genotype 1 chronic hepatitis C in adults with compensated liver disease [1].

Hepatitis C is a blood-borne virus that predominantly infects the cells of the liver. Transmission is by contact with infected blood primarily as a result of exposure through the skin to contaminated blood (for example, through intravenous drug use). The virus can cause inflammation of, and sometimes significant damage to, the liver and affect its ability to perform its many, varied and essential functions. A hepatits C infection can be categorised into 2 stages, firstly an acute infection (the first 6 months following initial infection) and secondly a chronic infection.

Figures from 2009 suggest that around 146,000 people were chronically infected with the hepatitis C virus. Genotype 1 is the most common subtype of hepatitis C in England and Wales - affecting 40-50% of people with hepatitis - and the most resistant to treatment. Poor diagnosis and compliance rates and a high annual incidence of new infection mean that CHC presents a major public health challenge, despite the availability of treatments that provide the opportunity to address this challenge.

The primary aims of treatment are to clear the virus from the blood to prevent progression of liver disease, and to prevent the transmission of the hepatitis C virus. Current NICE guidance [2] recommends pegylated interferon and ribavirin combination therapy for people with genotype 1 chronic hepatitis C.

Telaprevir inhibits the activity of the NS3/4A serine protease. Activity of this protease is essential for viral replication and may be partially responsible for the ability of the hepatitis C virus to evade clearance by the host immune system. The drug is administered orally. The final draft guidance for telaprevir recommends the drug as an option for the treatment of genotype 1 chronic hepatitis C in adults with compensated liver disease who are previously untreated or in whom previous treatment with peginterferon alfa and ribavirin has failed, including people whose condition has relapsed, partially responded or did not respond.

Commenting on the draft recommendations, Meindert Boysen, Programme Director Technology Appraisals at NICE, said: "Chronic hepatitis C can have a significant impact on a person's quality of life, particularly when if it progresses to the fibrosis and cirrhosis stage. Fear of transmitting the disease is also a concern, particularly for women of child-bearing age for whom there is a risk of transmitting the disease to their unborn child. The Committee heard that the current treatment regimen for chronic hepatitis C is often lengthy and that the side effects of treatment themselves can have a significant impact on daily life.

"The significant improvement in sustained virological response rates seen with telaprevir plus peginterferon alfa and ribavirin compared to peginterferon alfa and ribavirin alone, and its potential for shortening the treatment time from the full 48 week course needed for a virological response therefore represents a major benefit for people with chronic hepatitis C. The Committee also acknowledged the significant public health impact that a sustained virological response can have in reducing transmission of the hepatitis C virus to uninfected people. We are pleased to be able to recommend teleprevir as a cost effective use of NHS resources, alongside boceprevir for which positive draft guidance was published last week."

The draft guidance is now with consultees, who have the opportunity to appeal against it. NICE has not yet issued final guidance to the NHS.

Ends

Notes to Editors
References and explanation of terms
[1] Chronic hepatitis C infection causes initial inflammation of the liver that progresses through to gradual scarring (fibrosis) and then hardening of liver tissue (cirrhosis). Cirrhosis commonly occurs in two stages, compensated and decompensated. In the first stage of cirrhosis, the liver can compensate for the damage and still has the ability to function normally. When extensive damage occurs and the liver can no longer function normally, decompensation occurs.

[2] NICE has published the following related guidance on hepatitis C:

•Peginterferon alfa and ribavirin for the treatment of chronic hepatitis C (part review of NICE technology appraisal guidance 75 and 106). NICE technology appraisal guidance 200 (2010).
•Peginterferon alfa and ribavirin for the treatment of mild chronic hepatitis C. NICE technology appraisal guidance 106 (2006).
•Interferon alfa (pegylated and non-pegylated) and ribavirin for the treatment of chronic hepatitis C. NICE technology appraisal guidance 75 (2004).
About the draft guidance
1. Approximately 15% of those infected with hepatitis C virus will naturally clear the virus from their body and experience no long-term effects from the infection. However, for the remaining 85% a chronic infection will develop. 80%(68) of those who develop a chronic infection will remain stable but the remaining 20% (17) will go on to develop liver cirrhosis, of whom 25% (4) will either progress to hepatocellular carcinoma, require a liver transplant, or die.

2. Figures from 2009 suggest that around 250,000 people were infected with the hepatitis C virus, of whom 146,000 were chronically infected. Hepatitis C is more common in men and in people aged 25-44 years. In England, prevalence studies suggest that people of South Asian family origin are at an increased risk of having hepatitis C infection.

3. In 2008, the Department of Health estimated that 68,000 patients with hepatitis C infection had been diagnosed and 4,800 had been treated.

4. The aims of treatment are:

•To eradicate the hepatitis C virus in the individual
•To prevent progression of liver disease and development of liver cancer
•To prevent transmission of hepatitis C virus
5. The Committee accepted that the most plausible ICERs for telaprevir plus peginterferon alfa and ribavirin compared with peginterferon alfa and ribavirin alone were £18,000 and £10,000 per QALY gained for the previously untreated and previously treated patients.

6. Telaprevir is priced at priced at £1866.50 for a 1-week, 42-tablet pack (excluding VAT; ‘Monthly Index of Medical Specialities' [MIMS] January 2012). This equates to a maximum of £22,398 for a 12-week course of therapy. Costs may vary in different settings because of negotiated procurement discounts.

7. NICE is also appraising boceprevir (Victrelis, Merck Sharp & Dohme) for this indication.

8. The SMC has published guidance on telaprevir for this condition: www.scottishmedicines.org.uk/SMC_Advice/Advice/742_11_telaprevir_Incivo_experienced_patients/telaprevir_Incivo and www.scottishmedicines.org.uk/SMC_Advice/Advice/743_11_telaprevir_Incivo_naive_patients/telaprevir_Incivo

About NICE
The National Institute for Health and Clinical Excellence (NICE) is the independent organisation responsible for providing national guidance and standards on the promotion of good health and the prevention and treatment of ill health

NICE produces guidance in three areas of health:

•public health - guidance on the promotion of good health and the prevention of ill health for those working in the NHS, local authorities and the wider public and voluntary sector
•health technologies - guidance on the use of new and existing medicines, treatments, medical technologies (including devices and diagnostics) and procedures within the NHS
•clinical practice - guidance on the appropriate treatment and care of people with specific diseases and conditions within the NHS.
NICE produces standards for patient care:

•quality standards - these reflect the very best in high quality patient care, to help healthcare practitioners and commissioners of care deliver excellent services
•Quality and Outcomes Framework - NICE develops the clinical and health improvement indicators in the QOF, the Department of Health scheme which rewards GPs for how well they care for patients
NICE provides advice and support on putting NICE guidance and standards into practice through its implementation programme, and it collates and accredits high quality health guidance, research and information to help health professionals deliver the best patient care through NHS Evidence.

This page was last updated: 13 March 2012

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J&J’s Hepatitis C Drug Wins U.K. Cost Agency’s Backing

By Makiko Kitamura on March 15, 2012

Johnson & Johnson (JNJ)’s Incivo won the backing of the U.K.’s health-cost regulator in a draft recommendation for the treatment of hepatitis C.

The medicine, also known as telaprevir or Incivek, is a cost-effective option for chronically infected hepatitis C patients when used with older drugs peginterferon alfa and ribavirin, the National Institute for Health and Clinical Excellence said today in a statement. The agency advises the state-run National Health Service on which products represent value for money.

Hepatitis C affects as many as 170 million people globally, putting them at risk of developing liver cancer, according to the World Health Organization. The disease is most commonly transmitted through contaminated blood transfusions, organ transplants, contaminated syringes and needle-injected drug use, according to the WHO.

“The significant improvement in sustained virological response rates seen with telaprevir plus peginterferon alfa and ribavirin compared to peginterferon alfa and ribavirin alone, and its potential for shortening the treatment time from the full 48-week course needed for a virological response, therefore represents a major benefit for people with chronic hepatitis C,” Meindert Boysen, program director of technology appraisals at NICE, said in the statement.

About 146,000 people in England and Wales were chronically infected with hepatitis C in 2009, according to NICE. The draft recommendation applies to patients with genotype 1, which is found in as many as half of hepatitis C patients and is the most resistant to treatment, NICE said.

The agency also recommended Merck & Co. (MRK)’s Victrelis treatment for hepatitis C for the same use as telaprevir last week.

To contact the reporter on this story: Makiko Kitamura in London at mkitamura1@bloomberg.net 

To contact the editor responsible for this story: Phil Serafino at pserafino@bloomberg.net

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Janssen launch MYINCIVOTM support programme

Posted on:28 Feb 12

High Wycombe, UK, 27th February 2012: Janssen has today launched a new partnership with Bupa Home Healthcare which will support chronic genotype-1 hep C patients undergoing an INCIVO®(telaprevir) based treatment regimen (telaprevir in combination with peginterferon alfa and ribavirin).

Speaking at the launch of the MYINCIVO™ Support Programme, Dr Peter Barnes, Medical Director at Janssen stated: “We recognise that treatment for hep C can be challenging and demands significant commitment from patients. We also recognise that the addition of telaprevir, one of a new class of medicines which directly targets the hep C virus, to the current standard treatment adds another element of complexity. That is why today we are launching this programme to support patients 24 hours a day, 7 days a week for the full duration of their treatment if they are initiated on a telaprevir based treatment regimen.”

Before the introduction of protease inhibitors, of which telaprevir is the latest, treatment for genotype-1 chronic hep C cleared the virus in only about 50% of patients, leaving the other 50% without a successful outcome following 12 months of treatment¹. Clinical trials have shown that a telaprevir based regimen is more effective than standard treatment in all genotype-1 patient types, including those with compensated liver disease such as cirrhosis. The addition of telaprevir to the current standard treatment (i.e. peginterferon alfa and ribavirin) cleared the virus in a significantly greater number of those patients who had previously been untreated (79% vs 46%, p<0.0001). In patients who had relapsed after previous treatment nearly four times as many cleared the virus in the telaprevir arm (84% vs 22%, p<0.0001)^2,3,4. In addition, treatment naive patients and prior treatment relapsers who achieve undetectable levels of hep C virus RNA on testing at weeks 4 and 12 can have their total treatment duration reduced to 24 weeks from the current 48 weeks with standard treatment5. A key factor in achieving these results was good adherence to treatment⁵.

In developing the MYINCIVO™ Support Programme Janssen worked with Bupa Home Healthcare, healthcare professionals and patient support groups to ensure patients have access to confidential advice and support to help them adhere to their medication, to take care of themselves, stay motivated and in control while going through treatment. Most importantly, the MYINCIVO™ Support Programme is intended to complement the care being provided by a patient’s hep C specialist healthcare professional and helps with continuity of the patient’s care and support. The MYINCIVO™ Support Programme can also be accessed by patients’ partners, carers or family members as appropriate.

Dr Mehmood Syed, Medical Director at Bupa Home Healthcare stated: “Providing tailored support to get better health outcomes for the individual is at the heart of this programme. We want to empower patients so that they have more control over their health as well as provide them with dedicated medical expertise and support when they need it”.

The programme is personalised to the needs of the individual patient via the MYINCIVO™ case management platform and the MYINCIVO™ dedicated nurse team are experienced in, and trained to provide additional advice and support on many issues. The MYINCIVO™ support programme is completely confidential between the patient, their hep C specialist healthcare professional and BUPA. It includes support such as a SMS text dose reminder service (to promote adherence), health coaching (to motivate, promote adherence, health & wellbeing), advice and information including healthy living, foods to eat while on treatment and dealing with symptoms and side-effects specific to patients who have been prescribed a telaprevir-based regimen.

The overall safety and tolerability profile of telaprevir is based on the phase II and III clinical development programme. The most frequently reported moderate adverse reactions (incidence = 5.0%) were anaemia, rash, pruritus, nausea, and diarrhoea, and the most frequently reported severe adverse reactions (incidence = 1.0%) were anaemia, rash, thrombocytopenia, lymphopenia, pruritus, and nausea⁵.

Rash events were reported in 55% of patients with telaprevir based treatment compared with 33% in the control arm (peginterferon alfa and ribavirin only). More than 90% of rashes were of mild or moderate severity. Severe rashes were reported with telaprevir based treatment in 4.8% of patients. Rash led to discontinuation in 5.8% of patients. Anaemia was reported in 32.1% of patients compared with 15% in the control arm (peginterferon alfa and ribavirin only). It led to discontinuation in approximately 3% of patients⁵.

In the UK, it is estimated that 216,000 to 466,000 individuals are chronically infected with hepatitis C, a virus that is carried in blood and predominantly affects the liver, of which only 80,000 have been diagnosed^6,7. Chronic hep C poses a public health burden. It is an infectious disease, with often no symptoms, that can lead to severe liver conditions. Of those who develop chronic hepatitis C an estimated 30% will develop cirrhosis (deterioration of the liver), others will develop liver cancer, some of whom may require liver transplantation¹. Chronic hep C is the most common reason for liver transplants in Europe⁸.

* INCIVO® (telaprevir), a direct acting antiviral (DAA) protease inhibitor (PI), was co-developed by Vertex Pharmaceuticals and Tibotec, an affiliate of Janssen Pharmaceutical Companies of Johnson & Johnson, and the company responsible for marketing telaprevir in Europe.

For more information contact
Simon Goldsborough, Munro & Forster Mobile: +44 (0) 7973 272915
Ronan Collins, Janssen Mobile: +44 (0) 7876 257746
James Thompson, Bupa Home Healthcare Mobile: +44 (0) 7894 416 823

References
1. TA200: Peginterferon Alfa and Ribavirin for the treatment of chronic hepatitis C. Part review of NICE technology appraisal guidance 75 and 106. Issued September 2010
2. Jacobson, Ira M. Telaprevir for Previously Untreated Hepatitis C Virus Infection. N Engl J Med. 2011; 364; 2405-16.
3. Zeuzem, Stefan MD. Telaprevir for Retreatment of HCV Infection. N Engl J Med. 2011; 364; 2417-28.
4. Sherman 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.
5. Telaprevir Summary of Product Characteristics 2011.
6. Hepatitis C in the UK: Annual Report2011. London Health Protection Agency, July 2011
7. In The Dark: An audit of hospital hepatitis C services across England. The All-Party Parliamentary Hepatology Group, August 2010
8. Lang K, Weiner DB. Immunotherapy for HCV infection: next steps. Expert Rev Vaccines. 2008;7(7): 915-923

For more information:
http://www.janssen.co.uk/

Editor's Details
Janssen
Janssen
http://www.janssen.co.uk/

Last updated on: 28/02/2012 12:08:35

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Germany’s IQWiG sees added benefits for Incivo (Telaprevir)

Article | 24 January 2012

In an early benefit assessment pursuant to Germany’s Act on the Reform of the Market for Medicinal Products (AMNOG), the German Institute for Quality and Efficiency in Health Care (IQWiG), has examined whether Incivo (telaprevir) offers an added benefit compared with the present standard therapy.

According to the findings of the assessment, telaprevir offers advantages in various groups of patients with chronic hepatitis C infection of genotype 1. The available studies provide proof, indications or "hints” of an added benefit. However, not only the probability but also the extent of added benefit varies, said the IQWiG.

The European Commission has approved Johnson & Johnson (NYSE: JNJ) subsidiary Janssen’s Incivo, a direct acting antiviral (DAA) protease inhibitor, for the treatment of genotype-1 chronic hepatitis C virus (HCV), in combination with peginterferon alfa and ribavirin, in adults (The Pharma Letter September 21, 2011). The drug was developed in collaboration with the USA’s Vertex and Japan’s Mitsubishi Tanabe and is approved and marketed under the trade name Incivek in the USA and Canada (TPLs May 24 and August 23).

In accordance with the approval status, different patient groups are treated for different periods, which was allowed for in the assessment. The dual combination of peginterferon alfa and ribavirin is the present standard therapy, and this was compared with the triple combination of these two standard drugs and telaprevir.

Studies largely only provide data on morbidity and adverse effects

Overall three relevant studies were identified. The outcomes considered were "mortality,” "secondary complications of treatment (morbidity)” measured in the studies by means of the surrogate outcome "SVR,” as well as "health-related quality of life” and "adverse effects.”

The quality-of-life results for treatment-naive (ie, previously untreated) patients without cirrhosis were not statistically significant. No evaluable data on this outcome were available for other patient groups. Due to the too short study duration, the event rates for mortality were too low in all patient groups to be able to draw robust conclusions.

Extent of added benefit cannot be classified on the basis of the surrogate outcome for morbidity

The extent of added benefit cannot be classified on the basis of the surrogate outcome "SVR,” the agency noted. This parameter is not a patient-relevant outcome in itself and there are no studies in which SVR is validated as a surrogate outcome in accordance with the usual criteria employed by IQWiG. Nevertheless, the Institute accepts SVR in the context of this assessment as a surrogate for the reduced incidence of liver cancer. This is because it is currently accepted that patients with no detectable hepatitis C virus in the blood are at lower risk of liver cancer. However, it is not known how many cases of liver cancer can in fact be prevented by telaprevir and it is therefore unclear whether the added benefit can be classified as "minor” "considerable” or "major.” According to the corresponding legal ordinance, the added benefit is thus "unquantifiable.”.Under consideration of the beneficial and harmful effects of telaprevir, overall IQWiG reaches different conclusions for different patient groups.

Advantages for treatment-naive patients without cirrhosis who have a high viral load

Different results for morbidity were shown for treatment-naive patients without cirrhosis, depending on the viral load in the blood at the start of treatment. Proof of an added benefit of telaprevir was only determined for patients with a high viral load. However, the extent of the added benefit is unquantifiable as it refers to the surrogate outcome "SVR.”

For treatment-naive patients without cirrhosis, the data also provide proof and an indication of greater harm due to the adverse effects anaemia and rash, respectively, the extent being classified as "considerable” in the former and "minor” in the latter case. In the consideration of the beneficial and harmful effects of telaprevir, this did not lead to a restriction in the overall conclusion for patients with a high viral load, as these side effects were nearly exclusively classified as "not serious,” said the IQWiG.

In contrast, for treatment-naive patients without cirrhosis who have a low viral load at baseline, the data provide an indication of lesser benefit of telaprevir versus the comparator therapy. This is due to the fact that an added benefit regarding SVR is not proven, so that only the harmful effects are taken into account. An added benefit of telaprevir is not proven for treatment-naive patients with cirrhosis, as the manufacturer dossier did not contain any evaluable data.

Indication of an advantage also in patients with unsuccessful pre-treatment

Depending on the cirrhosis status, different results were shown for patients in whom treatment had so far been unsuccessful (non-responders). Regarding morbidity, the data provide an indication of an added benefit of telaprevir in patients without cirrhosis. The data only provide a "hint” of an added benefit in non-responders with cirrhosis. In this context, "indication” and "hint” refer to the surrogate outcome "SVR.” Therefore the extent of added benefit is unquantifiable. As in the case of treatment-naive patients without cirrhosis, indications of greater harm due to the side effects "anaemia” and "rash” did not lead to a restriction in the overall conclusion.

No additional benefit for relapsed patients

In patients without cirrhosis who relapsed after standard therapy, the treatment regimen deviated from the approval status. Consequently, the added benefit cannot be assessed on the basis of the available data so that an added benefit is not proven, noted the IQWiG.

In patients with cirrhosis who relapsed, the data provide an indication of an added benefit regarding SVR. However, at the same time they also provide an indication of greater harm (extent: considerable) regarding serious adverse events. Under consideration of the beneficial and harmful effects of telaprevir, the IQWiG concluded that overall an added benefit is not proven for this patient group.

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