Simeprevir as Effective, Better Tolerated than Telaprevir in HCV Triple Therapy

The recently approved next-generation hepatitis C virus (HCV) protease inhibitor simeprevir (Olysio) produced sustained virological response rates similar to those of telaprevir (Incivek or Incivo) when combined with pegylated interferon and ribavirin, but with fewer side effects, researchers reported at theViral Hepatitis Congress taking place this week in Frankfurt.

Many people with hepatitis C and their providers desire all-oral interferon free regimens that are easier to take and better tolerated, but in countries where newer direct-acting antivirals are not yet available, triple therapy with telaprevir or boceprevir (Victrelis) remains an option.

At this week's conference, researchers presented data from a subset of participants from Europe and Israel in the Phase 3 ATTAIN trial. This group had a slightly better response rates in both the simeprevir and telaprevir arms -- 58% and 60%, respectively -- than the study population as a whole.

Below is an edited excerpt from a Janssen press release describing the findings in more detail.

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.

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

10/10/14

Source

Janssen R&D. Janssen Demonstrates Continued Commitment to Combating Hepatitis C in European Patients With Data Presented at Viral Hepatitis Congress. Press release. October 10, 2014.