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Olysio/Simeprevir COSMOS, ATTAIN Study
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APASL/March 2014: A Phase III randomised, double-blind study to evaluate the efficacy, safety and tolerability of simeprevir vs telaprevir in combination with pegylated interferon and ribavirin in chronic hepatitis C virus genotype 1 treatment-experienced patients: the ATTAIN study.......
http://www.natap.org/2014/APASL/APASL_20.htm
(Q80K) Virology analyses of simeprevir in Phase 2b and 3 studies - (04/17/14)
EASL: Once-daily simeprevir (TMC435) plus sofosbuvir (GS-7977) with or without ribavirin in HCV genotype-1 prior null responders with METAVIR F0-2: COSMOS study subgroup analysis - (04/14/14)
EASL: Simeprevir plus sofosbuvir with/without ribavirin in HCV genotype-1 prior null-responder / treatment-na•ve patients (COSMOS study): primary endpoint (SVR12) results in patients with METAVIR F3-4 (Cohort 2) - (04/14/14)
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Janssen Demonstrates Continued Commitment to Combating Hepatitis C in European Patients With Data Presented at Viral Hepatitis Congress
New data demonstrates efficacy and safety of Olysio (simeprevir) in broader patient populations
Frankfurt, Germany -- October 10, 2014 -- 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).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.
The aim of the study was to demonstrate the non-inferiority of simeprevir versus telaprevir with pegIFN [pegylated interferon] and RBV [ribavirin] 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).
"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 programs, 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).
Anemia-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.
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-naive patients which indicated that simeprevir has a good renal safety profile. Furthermore, the post-hoc analysis of pooled efficacy data from the Phase 3 QUEST-1 and QUEST-2 studies of treatment-naive genotype 1 HCV patients, supported the use of simeprevir in combination with PegIFN/RBV to treat HCV patients with moderate liver fibrosis.
Janssen also presented an investigation of the prevalence of Q80k polymorphism in a pooled analysis of GT1 patients from telaprevir and simeprevir phase 2/3 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.
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.
About Janssen Pharmaceutical Companies
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, Janssen develops innovative products, services and healthcare solutions to help people throughout the world.
Janssen believes to effectively fight hepatitis C, a serious commitment is required from all stakeholders to improve the healthcare infrastructure across the continuum of care, increase awareness, provide education and ensure access to effective treatment for people living with hepatitis C. Janssen is working around the world to be a positive catalyst in the fight towards eradication of this deadly disease and serious public health problem.
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ATTAIN About the ATTAIN study
The multicenter phase III clinical study of treatment-experienced genotype 1 HCV patients partial- and null-responder patients to at least one previous course of PegIFN/RBV therapy called the ATTAIN study is a randomized, double-blind, two-arm study. In the trial, 771 patients were randomized (1:1) to treatment with either 150 mg of simeprevir once daily plus PegIFN/RBV or 750 mg of telaprevir three times per day plus PegIFN/RBV for 12 weeks, followed by 36 weeks of PegIFN/RBV alone.
Results from the ATTAIN study
Results from ATTAIN show that simeprevir achieved its primary endpoint of non-inferiority to telaprevir in treatment-experienced HCV patients and demonstrated a superior safety profile. In the study, 54 percent of chronic HCV genotype 1 prior partial- and null-responder patients treated with simeprevir administered once daily in combination with pegylated interferon and ribavirin achieved the primary endpoint of sustained virologic response 12 weeks after end of treatment (SVR12) compared to 55 percent of patients treated with telaprevir administered three-times daily plus pegylated interferon and ribavirin.
Among prior null-responder patients, 44 percent of patients in the simeprevir arm achieved SVR12 versus 46 percent of patients in the telaprevir arm. Among prior partial-responder patients, 70 percent of patients in the simeprevir arm achieved SVR12 versus 69 percent of patients in the telaprevir arm.
SVR12 rates across patient subgroups were generally similar between the simeprevir and telaprevir arms, including among patients with the HCV genotype 1a Q80K mutation. Twenty-seven percent of patients with the HCV Q80K mutation achieved SVR12 in the simeprevir arm versus 26 percent in the telaprevir arm. The study also found that 60 percent of patients with the IL28B CC genotype, 55 percent of CT patients and 48 percent of TT patients in the simeprevir arm achieved SVR12, versus 67, 57 and 50 percent of patients in the telaprevir arm, respectively.
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, including pruritus (31 percent versus 43 percent), fatigue (32 percent versus 38 percent), headache (25 percent versus 29 percent), anemia (13 percent versus 37 percent), and nausea (17 percent versus 28 percent). Thirty-four percent and 18 percent of simeprevir-treated patients experienced on-treatment failure and relapse, respectively, compared to 32 percent and 17 percent of telaprevir-treated patients, respectively. Two percent of patients in the simeprevir arm and eight percent of patients in the telaprevir arm discontinued treatment early due to an adverse event. Serious adverse events were reported in two percent of patients in the simeprevir arm and nine percent of patients in the telaprevir arm.
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