Janssen Pharmaceutica N.V. Release: INCIVO® (Telaprevir) SVR Rates Unaffected by Ribavirin Dose Reduction in Treatment Naïve and Previously Treated Patients With Genotype-1 Chronic HCV

BARCELONA, Spain, April 18, 2012 /PRNewswire/ --

- 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 21^st 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:

1. 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
2. Copegus® Summary of Product Characteristics, updated 2012
3. Jacobson, I et al. Telaprevir for Previously Untreated Hepatitis C Virus Infection. N Engl J Med. 2011;364:2405-16. (ADVANCE)
4. Sherman, K et al. Response-Guided Telaprevir Combination Treatment for Hepatitis C Virus Infection. N Engl J Med. 2011;365:1014-24. (ILLUMINATE)
5. Zeuzem,S et al. Telaprevir for Retreatment of HCV Infection. N Engl J Med. 2011;364:2417-28.(REALIZE)
6. Incivo® Summary of Product Characteristics, updated 2011
7. 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
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.
9. Centres for Disease Control and Prevention. Hepatitis C FAQs. [cited 2009 Dec 17] Available from: http://www.cdc.gov/hepatitis/C/cFAQ.htm#transmission.
10. 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
11. WHO. State of the art of vaccine research and development. Viral Cancers. Available from http://www.who.int/vaccine_research/documents/Viral_Cancers.pdf).
12. 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.
13. Lang K, Weiner DB. Immunotherapy for HCV infection: next steps. Expert Review of Vaccines 2008;7(7): 915-923.
14. 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.
15. 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