Janssen Infectious Diseases-Diagnostics BVBA (Janssen), has announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending the approval of twice daily (BID) dosing 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 (PR).
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. The current approved dose for INCIVO is 750mg every eight hours in combination with PR.
“This positive opinion from the CHMP is an important development for a more convenient treatment regimen for patients which should help lead to greater adherence, a critical factor in HCV treatment,” said Gaston Picchio, Hepatitis Disease Area Leader at Janssen R&D. “Telaprevir has already played a huge part in improving treatment outcomes for people living with hepatitis C with more than 80,000 people treated to date globally with telaprevir combination treatment. This recommendation is the next step in our commitment to improving the lives of more people living with hepatitis C and supporting healthcare professionals around the world.”
Janssen presented clinical trial results showing that the relative efficacy of a twice daily (BID) investigational dosing regimen of INCIVO® (telaprevir) 1125mg combination treatment was similar to an every eight hours (q8h) regimen of INCIVO® (telaprevir) 750mg combination treatment in HCV genotype-1 patients regardless of fibrosis or cirrhosis based on sustained virological response rates at 12 weeks after the last treatment dose (SVR12).(1) These results, a sub-analysis from the OPTIMIZE Phase 3 trial, were presented during the 48th annual meeting of the European Association for the Study of the Liver (EASL) in Amsterdam (http://www.easl.eu/_the-international-liver-congress). Additional sub-analyses from this study evaluating anaemia management,(2) efficacy in patients by the IL28B genotype(3) and patient adherence(4) were also presented.
“Simplifying available treatment regimens for HCV, without compromising on cure rates is especially important for patients with fibrosis or cirrhosis. We know that telaprevir combination treatment offers patients improved cure rates over treatment with pegylated interferon and ribavirin alone. These results confirm that a twice daily dosing schedule for a telaprevir-based regimen gives patients a similar chance of achieving SVR12 as the current approved dose in a population who desperately need more effective treatment,” said Yves Horsmans, Lead Study Investigator and Professor at Cliniques Universitaires Saint-Luc, Belgium.
Results from the sub-analysis of the 740 patients included in the OPTIMIZE study showed that those with cirrhosis who received a twice daily dose of telaprevir 1125mg in combination with PR, achieved similar SVR12 rates compared with those who received telaprevir 750mg every eight hours in combination with PR (54% versus 49%).(1) Patients at other stages of fibrosis, F0 to F4, also achieved similar SVR12 rates with a twice daily dose of telaprevir 1125mg in combination with PR compared with those who received telaprevir 750mg every eight hours in combination with PR (see table 1).
The safety and tolerability of telaprevir across fibrosis or cirrhosis stages were consistent with previous studies.(1) Grade 3 or 4 adverse events (AEs) were reported in 41% of patients with and 40% of patients without cirrhosis.(1) Serious adverse events and discontinuations due to adverse events were higher in patients with cirrhosis than those without (14% and 21% vs 8% and 16%, respectively).(1) The most common adverse events experienced were fatigue, pruritus, anaemia, nausea and rash.(5) The proportion of patients who experienced a low haemoglobin level (≤10g/dL) was higher among patients with (50%) than without cirrhosis (42%).(1)
Results from an additional sub-analysis of the OPTIMIZE study found that adherence was greater in patients who received twice daily dosing of telaprevir compared to every eight hours.(4) “Treating HCV can be complex and therefore anything that can help make effective treatments simpler and adherence easier for patients will ultimately improve their chance of achieving a cure,” said study investigator Dr Maria Buti, Hospital Val d’Hebron, Spain.
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) Poster 985.
Zeuzem S, Buti M, Agarwal K et al. Anemia and its management in patients treated with telaprevir twice-daily versus every 8 hours in the Phase III OPTIMIZE study. 2013. European Association for the Study of the Liver (EASL) Abstract 919.
Buti M, Agarwal K, Horsmans Y. Efficacy of telaprevir dosed twice daily versus every 8 hours by IL28B genotype: results from the Phase III OPTIMIZE study. 2013. European Association for the Study of the Liver (EASL) Abstract 798.
Sievert W, Buti M, Agarwal K. Adherence with telaprevir BID vs q8h dosing in treatment-naïve HCV-infected patients: results from the Phase III OPTIMIZE study. 2013. European Association for the Study of the Liver (EASL) Abstract 905.
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.LB-8