10 Results of a Proof of Concept Study (C210) of Telaprevir Monotherapy and in Combination With Peginterferon Alfa-2a and Ribavirin in Treatment-Naive Genotype 4 HCV Patients

Benhamou, Yves; Moussalli, J.; Ratziu, Vlad; Lebray, Pascal; Gysen, V.; Backer, K. de; Ghys, A; Heeswijk, Rolf van; Vangeneugden, Tony; Picchio, Gastón; Beumont–Mauviel, Maria

doi:10.1016/s0168-8278(09)60012-x

Cited by 53 publications

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“…Significant genetic differences between genotypes 1 and 3 explain that the activity of protease inhibitors and that the potency of non-nucleoside polymerase inhibitors is either low or inexistent against genotype 3 37 . Activity against genotypes 2 and 4 can be identified, although it is usually very low.…”

Section: The Future Of Chronic Hepatitis C Treatmentmentioning

confidence: 99%

Perspectivas futuras en el tratamiento de la hepatitis crónica C

Fernández-Montero¹,

Soriano²

2011

Rev. esp. sanid. penit.

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The main lines of research into new drugs and treatment strategies against type C viral hepatitis are described. This disease is a major public health problem, with more than 700,000 people affected by the illness in Spain and with a high degree of prevalence amongst prison inmates. Limitations on current treatment for viral hepatitis C have led to research into new drugs in the form of two main product lines, some of which are soon to be available on the market: NS3/4ª serine-protease inhibitors (telaprevir, boceprevir, danoprevir and vaniprevir) and the NS5B RNA polymerase inhibitors (RG-7128, RG-7227, Filibuvir, ANA-598). The latter are in a somewhat earlier stage of development. It is expected that these new drugs will have to be used alongside the current standard treatment of pegylated interferon plus ribavirin and under these conditions of use the new drugs have already shown greater effectiveness than the current standard treatment. Despite this encouraging perspective, the new medicines have limitations such as the development of resistances, toxicity, and the little knowledge available of their effectiveness on viral genotypes that are different from 1. That being said, their appearance opens up new possibilities in the treatment of this disease.

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Section: The Future Of Chronic Hepatitis C Treatmentmentioning

confidence: 99%

Perspectivas futuras en el tratamiento de la hepatitis crónica C

Fernández-Montero¹,

Soriano²

2011

Rev. esp. sanid. penit.

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“…Telaprevir binds the NS3/4A protease of HCV GT 2, 3, and 4 with lower affinity, and data both from phase 1 monotherapy studies examining HCV viral load declines on telaprevir alone and from phase 2 combination therapy regimens suggest that while telaprevir has activity against GT 2 virus, its activity against GT 3 and 4 virus is limited [5,11,12].…”

Section: Treatment Naïvementioning

confidence: 99%

New Frontiers of HCV Therapy in HIV/HCV Co-infection

Amorosa

2010

Curr HIV/AIDS Rep

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“…[16] Phase II : Preliminary results of a proof-ofconcept, phase IIa (C210; NCT00580801) study indicated that telaprevir plus peg-IFN alfa-2a plus RBV showed greater antiviral activity than telaprevir monotherapy or peg-IFN alfa-2a plus RBV alone in treatment-naive patients with hepatitis C genotype 4. [76,77] Among hepatitis C genotype 2 and genotype 3 subjects receiving telaprevir monotherapy in a phase IIa study, six and three patients, respectively, developed a viral breakthrough by day 15; no viral breakthroughs were observed in the TPR2&PR22 arm. Viral breakthroughs were associated with viral variants with decreased susceptibility to telaprevir.…”

Section: Combination Therapymentioning

confidence: 99%

“…Between 41% and 72% of patients randomized to receive treatment with a 24-week telaprevir-based regimen maintained undetectable viral load at 12 weeks post-treatment. [65] Earlier interim results of PROVE 3 had shown that 60 [59,61,78,87] 16 April 2010 Efficacy and adverse events data from a phase II rollover trial (Study 107) in treatment-experienced patients with hepatitis C presented at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL-2010) [36,37] 9 April 2010 Final efficacy data added from the phase IIb trial (PROVE 3) in patients with hepatitis C who have failed prior therapy [88,89] 6 Mitsubishi Tanabe Pharma and Vertex Pharmaceuticals amend agreement for the development and commercialization of telaprevir in Asia [7] 10 July 2009 The rights to milestone payments for telaprevir in the EU are available for purchase (http://www.vrtx.com) [14,46,47] 26 April 2009 Antimicrobial data from an in vitro study in hepatitis C presented at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL-2009) [67] Continued next page [77,79] 26 April 2009 Interim efficacy data from a phase IIa, C210 trial in hepatitis C presented at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL-2009) [76,77] 25 April 2009 Efficacy data from an intent-to-treat analysis of a phase II trial (PROVE 3) in hepatitis C presented at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL-2009) [41,90] 31 [66] 17 October 2008 Tibotec initiates enrollment in the phase III, REALIZE trial for hepatitis C (treatment-experienced patients) in the US [56] 12 May 2005 Data from a media release have been added to the adverse events and viral infections therapeutic trials sections [55,57] 11 November 2004 Phase-Ib clinical trials in hepatitis C treatment in Europe (PO)…”

Section: Provementioning

confidence: 99%

Telaprevir

2010

Drugs R D

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Telaprevir (LY 570310; LY570310; MP 424; VX 950; is an orally administered peptidomimetic inhibitor of the hepatitis C virus (HCV) protease NS3/4A. It is being developed by Vertex Pharmaceuticals and its licensees for the treatment of HCV infections and has recently been submitted to the US FDA for approval. As the first ever HCV protease inhibitor in phase III development, it is being studied in trials in combination therapy with pegylated interferon alfa-2a and ribavirin in Europe, the US, Australia, Canada, and Puerto Rico in treatment-naive and treatmentexperienced patients with HCV genotype 1 infection. Phase III trials of telaprevir as combination therapy are also in progress in Japan. This review discusses the key development milestones and therapeutic trials of this drug to date. IntroductionTelaprevir is an orally administered peptidomimetic inhibitor of the hepatitis C virus (HCV) protease NS3/4A. It is being developed by Vertex Pharmaceuticals and its licensees, Janssen Pharmaceutica, Tibotec, as well as Mitsubishi Tanabe Pharma Corporation (formerly Mitsubishi Pharma Corporation), for the treatment of HCV infections. A rolling new drug application (NDA) submission is underway in the US in this indication. Telaprevir is the first ever HCV protease inhibitor to begin phase III development. The agent is being studied in phase III trials as part of combination therapy with pegylated interferon (peg-IFN) alfa-2a and ribavirin (RBV) in Europe, the US, Australia, Canada, and Puerto Rico in treatment-naive and treatment-experienced patients with HCV genotype 1 infection, the most difficultto-treat variant of the disease. Phase III trials of telaprevir as combination therapy are also in progress in Japan. A phase II study of telaprevir in combination with the HCV NS5B polymerase inhibitor VX 222 is in progress in the US. Phase II development of telaprevir as a monotherapy is also ongoing in various countries.NS3/4A protease activity is essential for viral replication and is partially responsible for the ability of HCV to evade clearance by the immune system of the host. Therefore, protease inhibition could offer a double hit strategy against HCV. Company AgreementsIn June 2006, Vertex entered into a license, development, manufacturing, and commercialization agreement with Janssen Pharmaceutica (a subsidiary of Johnson & Johnson). Under the collaboration agreement, Vertex will collaborate with Janssen to develop and commercialize telaThis drug profile has been extracted from Wolters Kluwer's AdisÔ R&D Insight drug pipeline database. R&D Insight tracks and evaluates drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch. This is an open access article published under the terms of the Creative Commons License ''Attribution-NonCommercial-NoDerivative 3.0'' (http://creativecommons. org/licenses/by-nc-nd/3.0/) which permits non-commercial use, distribution, and reproduction, provided the original work is properly cited an...

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10 Results of a Proof of Concept Study (C210) of Telaprevir Monotherapy and in Combination With Peginterferon Alfa-2a and Ribavirin in Treatment-Naive Genotype 4 HCV Patients

Cited by 53 publications

References 0 publications

Perspectivas futuras en el tratamiento de la hepatitis crónica C

Perspectivas futuras en el tratamiento de la hepatitis crónica C

New Frontiers of HCV Therapy in HIV/HCV Co-infection

Telaprevir

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