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Medivir HCV Report: Nucleotide Preclinical Development Started
  Key news from the ongoing Capital Markets Day

15-Nov-11 Medivir AB (OMX: MVIR), a research-based speciality pharmaceutical company focused on infectious diseases, reports the following key news concerning their hepatitis C projects.

Medivir programmes in collaboration with Tibotec Pharmaceuticals Medivir and Tibotec Pharmaceuticals have two programmes for the development of antiviral therapies for future treatment of hepatitis C (HCV), these are based on the HCV protease and polymerase drug targets.

In the protease project, TMC435 is in global phase III development in both treatment naïve and in patients that have relapsed after previous treatment with pegylated interferon (PegIFN) and ribavirin (RBV) in patients with chronic hepatitis C genotype 1.

The HCV polymerase collaboration program consists of two early development projects, a nucleoside and a nucleotide inhibitor.

TMC435 (NS3/4A protease inhibitor) presently in development in Hepatitis C genotype 1 infected patients.

Phase IIb studies

Final SVR24 data from the phase IIb study PILLAR, in treatment-naïve patients, was presented last week at the the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco, CA, USA. Results from this final PILLAR analysis showed that TMC435 administered in combination with peginterferon α-2a and ribavirin (PR) resulted in significantly higher sustained virologic response (SVR) rates compared to placebo plus PR, with the majority of TMC435 patients able to shorten total treatment duration to 24 weeks based on response-guided therapy.

· In the 150 mg TMC435 treatment groups, 81-86 percent of patients achieved SVR24, compared to 65 percent of patients treated in the placebo arm. In addition, 86 percent of patients in the TMC435 treatment arms had a shortened treatment duration of 24 weeks, compared to a 48 weeks treatment duration for patients who received placebo plus P/R.

· The once daily dosed TMC435 was generally safe and well tolerated at all doses and treatment durations.

Medivir recently issued a press release on final results from phase IIb study ASPIRE

This trial evaluated TMC435 once daily in addition to pegylated interferon (PegIFN) and ribavirin (RBV) in patients with chronic hepatitis C whose prior treatment with PegIFN and RBV was unsuccessful either because they relapsed, had a partial response or had a null response.

· Data from the ASPIRE study showed that patients in each of these subgroups who were treated with TMC435-based combination therapy achieved superior rates of sustained virologic response (viral cure) compared to those retreated with pegylated-interferon and ribavirin alone.

· All TMC435 subgroups achieved substantially higher viral cure rates (SVR24) compared to control group (PegIFN and RBV alone): 85% vs. 37% in prior relapsers, 75% vs. 9% in prior partial responders and 51% vs. 19% in prior null responders.

The once daily TMC435 was generally safe and well tolerated at all doses and treatment durations.

Phase III studies

SVR12 - new endpoint

· In the ongoing phase III studies in naïve and patients that have relapsed following previous treatment, the primary endpoint has been changed from SVR24 to SVR12 following recent discussions with the FDA. These studies (QUEST 1 &2 and PROMISE) were all fully recruited in August.

Phase III study in non-responder patients to be initiated

· Phase III study in prior partial and null responder HCV genotype 1 patients will start within six months. This study will evaluate efficacy, safety and tolerability for TMC435 vs telaprevir in combination with PegINFα-2a and Ribavirin in chronic Hepatitis C patients.

Phase II interferon free combination study with TMC435 and PSI-7977

This interferon free phase II combination study will commence shortly. It will evaluate TMC435 and PSI-7977 in combination with and without ribavirin for 12 and 24 weeks in genotype 1 patients who had a prior null response to Peg-IFN/RBV. The study design is now posted on

HCV polymerase collaboration

TMC649128 TMC649128, the first NS5B nucleoside polymerase inhibitor under the collaboration, entered into clinical development in Q1-2011. It was safe and well tolerated at all doses tested for up to 14 days. However the antiviral activity failed to meet the target product profile and therefore the clinical development has now been discontinued.

Nucleotide program

The focus of HCV polymerase collaboration is now on a liver targeted nucleotide polymerase inhibitor program. A clinical candidate has been selected and the project is now in preclinical development stage.

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