New data demonstrates efficacy and safety of Olysio (simeprevir) in broader patient populations

Janssen R&D Ireland (Janssen) today announced the presentation of additional data for the NS3/4A protease inhibitor OLYSIO^® (simeprevir) at the Viral Hepatitis Congress (VHC) in Frankfurt, Germany. The data includes new analysis of a European and Israeli Hepatitis C (HCV) patient subset within the previously presented ATTAIN Phase 3 study. Additional data presented investigates treatment considerations for a broad range of patient populations including the renal function of those treated with simeprevir as well as the prevalence of the polymorphism of Q80k in European genotype 1 (GT1) patients.

The new analysis of the Phase 3 ATTAIN study (n=763), showed sustained virological response at 12 weeks (SVR12) to be similar in European and Israeli patients compared to previous analysis of the overall patient population (GT1, null and prior responder patients).^[1] Importantly these results have shown that Week 4 response rates are a good predictor of SVR12, showing that the majority of patients treated with simeprevir and pegIFN/ RBV with HCV RNA <25 IU/ml at Week 4, were likely to achieve SVR by week 12.2

The aim of the study was to demonstrate the non-inferiority of simeprevir versus telaprevir with pegIFN and RBV in difficult to cure HCV genotype 1-infected patients who were null or partial responders to prior pegIFN and RBV therapy. Overall, simeprevir met its primary endpoint of non-inferiority to telaprevir in treatment-experienced HCV patients and also demonstrated an improved tolerability profile, with SVR12 rates within the European cohort reported at 58 percent for the simeprevir arm and 60 percent for the telaprevir arm (compared to 54% and 55% respectively in the total patient population).^[1],[2]

“The new ATTAIN data presented at the Viral Hepatitis Congress adds to the breadth of data that highlights the value of simeprevir, in combination with pegylated interferon and ribavirin, as well as helping to further define patients who can benefit from this therapy,” said PD Dr. med. Holger Hinrichsen, Centre for Gastroenterology and Hepatology, Kiel, Germany and investigator of the ATTAIN study. “While interferon-free regimens are a focus of industry clinical development programmes, these results demonstrate that interferon based therapies still have an important role to play within current standards of treatment.”

The most common adverse events during the first 12 weeks of treatment occurred at a consistently lower frequency in the simeprevir treatment arm compared to the telaprevir treatment arm. Adverse events included: pruritus (31 percent versus 43 percent); fatigue (32 percent versus 38 percent); headache (25 percent versus 29 percent) and anemia (13 percent versus 37 percent).

Anaemia-related blood transfusions were significantly lower in the simeprevir treatment arm (0.8%) versus the telaprevir treatment arm (9.1%). Only two percent of patients in the simeprevir arm versus eight percent of patients in the telaprevir arm discontinued treatment early due to an adverse event.²

Breadth of data shows promise for diverse patient populations Additional data also presented at VHC investigated the renal function in patients treated with simeprevir or placebo in combination with Peg-IFN/ribavirin (PR) in HCV genotype-1-infected, treatment-naïve patients which indicated that simeprevir has a good renal safety profile.^[3] Furthermore, the post-hoc analysis of pooled efficacy data from the Phase 3 QUEST-1 and QUEST-2 studies of treatment-naïve genotype 1 HCV patients, supported the use of simeprevir in combination with PegIFN/RBV to treat HCV patients with moderate liver fibrosis.^[4]

Janssen also presented an investigation of the prevalence of Q80k polymorphism in a pooled analysis of GT1 patients from telaprevir and simeprevir phase II/III clinical trials. This analysis establishes that there is a considerably lower prevalence of the Q80k polymorphism at baseline among patients infected with HCV GT1 in European countries, compared to a previous analysis in North American patients. This analysis demonstrated that within Europe, the prevalence of Q80k polymorphism varies considerably between countries, due in part to the different prevalence of GT1b (which does not contain the Q80k polymorphism) as well as the differing prevalence of Q80k in GT1a across the European region.^[5]

“Hepatitis C affects a diverse patient population across a range of genotypes,” said Dr. PhD Michael Schlag, Medical Affairs Director, simeprevir, Janssen EMEA. “As the Hepatitis C treatment landscape has evolved, we must look to expand our understanding of how new drugs will work for individual patients with the aim of providing tailored treatments for patients that results in improved outcomes. These additional data presented by Janssen at the Viral Hepatitis Congress demonstrates our dedication to keeping the patient at the heart of ongoing advances.”

About simeprevir

Simeprevir is an NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB and indicated for the treatment of chronic hepatitis C infection as a component of a combination antiviral treatment regimen. Simeprevir efficacy has been established in HCV genotype 1 and 4 infected patients with compensated liver disease, including cirrhosis.^[6]

Janssen is responsible for the global clinical development of simeprevir and has exclusive, worldwide marketing rights, except in the Nordic countries. Medivir AB retains marketing rights for simeprevir in these countries under the marketing authorization held by Janssen-Cilag International NV. Simeprevir was approved for the treatment of chronic hepatitis C infection as part of an antiviral treatment regimen in combination with PegIFN + RBV in genotype 1 infected adults with compensated liver disease, including cirrhosis in September 2013 in Japan, in November 2013 in Canada and the U.S., in March 2014 in Russia, and in July 2014 in Mexico and Australia. In May 2014 simeprevir was granted marketing authorization by the European Commission (EC) for the treatment of adult patients with genotype 1 or genotype 4 chronic HCV.

Date of preparation: September 2014

References

1. Simeprevir versus telaprevir in combination with pegylated interferon and ribavirin in HCV genotype 1-infected patients: the Phase III ATTAIN study. Hinrichsen, H et al. Presentation at VHC, October 2014
2. Simeprevir versus telaprevir in combination with pegylated interferon and ribavirin in HCV genotype 1-infected patients: the Phase III ATTAIN study. Hinrichsen, H et al. Abstract presented at VHC, October 2014.
3. Renal function in HCV genotype 1-infected treatment-naïve patients receiving simeprevir in combination with Peg-IFN and ribavirin: a post-hoc analysis. Mauss, S et al. Abstract presented at VHC, October 2014
4. Efficacy and safety of simeprevir in treatment-naïve HCV genotype-1 infected patients with METAVIR F2 fibrosis: QUEST 1 and QUEST 2 Phase III studies. Abstract presented at VHC, October 2014.
5. Prevalence of the hepatitis C virus polymorphism Q80K in a pooled analysis of G1 patients from telaprevir and simeprevir phase II/III clinical trials. Lenz O et al. Abstract presented at VHC, October 2014.
6. Simeprevir summary of product characteristics. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR__Product_Information/human/002777/WC500167867.pdf Last accessed October 2014
7. European Association for the Study of the Liver. EASL The Burden of Liver Disease in Europe. Available from http://www.easl.eu/assets/application/files/54ae845caec619f_file.pdf. Accessed April 2014.
8. EASL Recommendations on Treatment of Hepatitis C 2014, European Association for the Study of the Liver, Journal of Hepatology 2014 vol. 60 j 392–420
9. World Health Organisation. Hepatitis C. Fact sheet N. 164. Available at: http://www.who.int/mediacentre/factsheets/fs164/en/ Accessed September 2014.
10. Muhlberger M et al. HCV-related burden of disease in Europe: a systematic assessment of incidence, prevalence, morbidity, and mortality. BMC Public Health 2009:9,34.
11. World Health Organisations (WHO). “Hepatitis C: About HCV Infection.” Available at: www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index3.html Accessed March 2014.
12. World Health Organisation. Hepatitis C. Available at: http://www.who.int/csr/disease/hepatitis/Hepc.pdf. Accessed March 2014
13. Zein NN. Clinical Significance of Hepatitis C Virus Genotypes. Clin. Microbiol. Rev. April 2000:13(2),223-235.