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Phase II all-oral combination studies of Simeprevir (TMC435), TMC647055 (non nuc polymerase inhibitor) and IDX719 (NS5A) for the treatment of Hepatitis C to be initiated shortly - 4 articles below
  press release 28-Jan-13 Stockholm, Sweden -

STOCKHOLM--Jan 28, 2013 - Regulatory News: Medivir AB today announced a non-exclusive collaboration between Janssen Pharmaceuticals Inc. (Janssen) and Idenix Pharmaceuticals for the clinical development of an all-oral (interferon-free) direct-acting antiviral (DAA) hepatitis C (HCV) combination therapy. The collaboration will evaluate combinations including simeprevir (TMC435), a once-daily protease inhibitor jointly developed by Janssen R&D Ireland and Medivir, TMC647055, a potent once-daily NNI (non-nucleoside inhibitor) of the HCV polymerase, boosted with low dose ritonavir, being developed by Janssen and IDX719, Idenix's once-daily pan-genotypic NS5A inhibitor.

Clinical development plans include an initial drug-drug interaction study to begin in the first quarter of 2013, followed by phase II studies as agreed between the companies, and pending approval from regulatory authorities. The phase II program is expected to first evaluate the two-DAA combination of IDX719 and simeprevir plus ribavirin for 12 weeks in treatment-naïve HCV-infected patients. Subsequently, the companies plan to evaluate a three-DAA combination of IDX719, simeprevir, TMC647055/r, with or without ribavirin. The clinical trials will be conducted by Idenix. Both companies retain all rights to their respective compounds under this agreement.

"This collaboration agreement underscores our strong commitment to develop interferon-free treatment options with simeprevir as a base for hepatitis C patients", says Charlotte Edenius, EVP of Research and Development, Medivir AB. "We are committed to develop these new treatments, where already four different interferon-free combinations with simeprevir are under investigation, with the potential to achieve high viral cure rates after only 12 weeks of total treatment, and we look forward to start this new collaboration with Idenix."

About Simeprevir (TMC435) Simeprevir is a once-daily potent investigational hepatitis C protease inhibitor in late phase III clinical development being jointly developed by Janssen R&D Ireland and Medivir AB to treat chronic hepatitis C virus infections. Simeprevir is being investigated in combination with PegIFN/RBV in phase III trials and is also being evaluated with Direct-acting Antiviral (DAA) agents in four other phase II interferon-free combinations both with and without ribavirin (RBV).

Global phase III studies of simeprevir in combination with PegIFN/RBV include the following studies:

· QUEST-1 and QUEST-2 in treatment-naïve patients.

· PROMISE in patients who have relapsed after prior interferon-based treatment.

· ATTAIN in prior null-responder patients and studies in Japanese HCV genotype 1 patients.

In parallel to these trials, phase III studies for simeprevir are ongoing in treatment-naïve and treatment-experienced HIV-HCV co-infected patients and in HCV genotype 4 patients.

Simeprevir is also being studied in phase II interferon-free trials both with and without ribavirin:

· Simeprevir in combination with Gilead Sciences' sofosbuvir (GS7977) in hepatitis C genotype 1 treatment-naïve or prior null responder patients.

· Simeprevir in combination with BMS's, daclatasvir in hepatitis C genotype 1 treatment-naïve or prior null responder patients.

· Simeprevir in combination with Janssen's TMC647055 and low dose ritonavir in hepatitis C genotype 1 treatment-naïve, prior relapser or null responder patients.

· Simeprevir in combination with Vertex's VX-135 in hepatitis C genotype 1 treatment-naïve patients to commence in 2013.

For additional information about simeprevir, please visit www.clinicaltrials.gov

About IDX719

IDX719 is an NS5A inhibitor with low picomolar, pan-genotypic antiviral activity in vitro. To date, IDX719 has been safe and well tolerated after single and multiple doses of up to 100 mg in healthy volunteers (n=36; up to 7 days duration) and HCV-infected patients (n=69; up to 3 days duration). There have been no treatment-emergent serious adverse events reported in the program. IDX719 has demonstrated potent pan-genotypic antiviral activity in HCV-infected patients with mean maximal viral load reductions up to approximately 4.0 log10 IU/Ml across HCV genotypes 1-4 in a proof-of-concept, three-day monotherapy study. For more information about IDX719, please visit www.idenix.com.

About TMC647055

TMC647055 is a potent non-nucleoside hepatitis C polymerase inhibitor with broad genotypic coverage. TMC647055 is in phase II clinical development and is developed by Janssen R&D Ireland to treat chronic hepatitis C virus infections. TMC647055 is being investigated in combination with other DAA agents in all oral interferon-free regimens. There have been no treatment-emergent serious adverse events reported in the program.


Idenix Update Slides - IDX184 Nucleotide, new IDX719 NS5A (slides attached from investor call this morning), 2 new nucleotides in development (IDX19368/IDX19370)



A Phase IIa Interferon Free Combination Hepatitis C Trial of Simeprevir (TMC435) and TMC647055 Will Commence Shortly

STOCKHOLM, September 20, 2012 /PRNewswire/ --

Medivir AB (OMX: MVIR), announced today that simeprevir (TMC435) and TMC647055, a non-nucleoside inhibitor (NNI) will enter a phase IIa interferon free combination trial.

Simeprevir is a once daily potent HCV NS3/4A protease inhibitor in phase III clinical development for the treatment of chronic hepatitis C jointly developed by Medivir and Janssen Research & Development Ireland (Janssen). TMC647055 is a potent NNI (non-nucleoside inhibitor) of the HCV NS5B polymerase and is being developed by Janssen R&D.

"This study is in line with Medivir's and Janssen's strategy to evaluate different combination possibilities with simeprevir for interferon-free HCV treatments. This will broaden our understanding of simeprevir, which we believe has the necessary characteristics to potentially become a key component of future hepatitis C treatment regimens, including combination with interferon and ribavirin as well as interferon-free therapies," comments Charlotte Edenius , Medivir's EVP of Research and Development.

Study design

This will be an open label study in patients who are chronically infected with HCV genotype-1a or 1b to assess the efficacy, safety and tolerability of the combination. The primary endpoint in the study will be SVR12 (sustained virologic response 12 weeks after end of treatment). Simeprevir, TMC647055 and low-dose ritonavir will be co-administered once daily, with and without ribavirin.

Approximately 40 patients will be enrolled in this study, which is divided in two parts. The first part will include patients chronically infected with HCV genotype-1, who are either treatment-naive or have relapsed after prior pegylated interferon (PegIFN)/ribavirin treatment. The treatment will consist of simeprevir, TMC647055 and low-dose ritonavir, with and without ribavirin for 12 weeks.

The second part of the trial will investigate the same regimen in prior null responder patients chronically infected with HCV genotype 1a.

Additional information about this study will be posted on http://www.clinicaltrials.gov


Idenix Announces Positive Clinical Data for HCV Drug Candidates IDX184 and IDX719

In an Interim Analysis From an Ongoing Phase IIb Clinical Trial of IDX184, an HCV Nucleotide Inhibitor, 89% of Patients Who Completed an Additional 12 Weeks of Pegylated Interferon Plus Ribavirin Treatment Achieved SVR4; 100% (4/4) in 100 mg Arm and 80% (4/5) in 50 mg Arm

IDX719, an HCV NS5A Inhibitor, Achieves Potent Pan-Genotypic Activity in Three-Day Proof-of-Concept Clinical Trial

CAMBRIDGE, Mass., June 19, 2012 (GLOBE NEWSWIRE) -- Idenix Pharmaceuticals, Inc. (Nasdaq:IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced results from an ongoing phase IIb study of IDX184 in combination with pegylated interferon and ribavirin (PegIFN/RBV). Of the first cohort of 31 patients enrolled in the study, those who achieved an eRVR (n=18), defined as having undetectable levels of virus at 4 weeks and 12 weeks, were randomized to stop treatment after either an additional 12 weeks (n=9) or 36 weeks (n=9) of PegIFN/RBV. Of the nine patients who completed their 12-week PegIFN/RBV extended treatment phase, 100% of patients (4/4) in the 100 mg arm and 80% of patients (4/5) in the 50 mg arm achieved a sustained virologic response four weeks after the completion of treatment (SVR4). Patients who did not achieve an eRVR automatically entered the 36-week PegIFN/RBV extended treatment phase which is ongoing. To date, the side effect profile of IDX184 combined with PegIFN/RBV is consistent with that of PegIFN/RBV alone.

"We are encouraged by the initial SVR results from the phase IIb program, which have confirmed previous data showing that IDX184 is a potent nucleotide inhibitor with a profile supporting its potential role as a key component of all-oral direct-acting antiviral (DAA) combination regimens for HCV," stated Ron Renaud, President and Chief Executive Officer of Idenix. "We look forward to initiating interferon-free DAA combination studies in the near term."

IDX184 Phase IIb Study Design

In July 2011, the company initiated enrollment of treatment-naive genotype 1 HCV-infected patients into a randomized, double-blind, parallel group phase IIb clinical trial of IDX184. The study features two treatment arms, either 50 mg or 100 mg of IDX184 administered once-daily for 12 weeks, each arm in combination with PegIFN/RBV. Response-guided therapy was used to complete an additional 12 or 36 weeks of PegIFN/RBV treatment. Study objectives include safety and tolerability, and antiviral activity endpoints.

IDX719 Proof-of-Concept Clinical Trial Data and Study Design

Idenix also announced today positive data from a three-day proof-of-concept study evaluating IDX719, an NS5A inhibitor, in 64 treatment-naïve, genotype 1, 2, 3 or 4 HCV-infected patients. Genotype 1 patients were randomized to receive placebo, 25 mg QD (once-daily), 50 mg QD, 50 mg BID (twice-daily) or 100 mg QD for three days. Genotype 2, 3 or 4 patients were randomized to receive placebo, 50 mg BID or 100 mg QD for three days.

IDX719 was well tolerated with no serious adverse events reported. Treatment with IDX719 exhibited potent pan-genotypic activity across genotypes:

· In genotype 1 patients (n=28), mean maximal viral load reductions were 3.2 log10 IU/mL in the 25 mg QD arm, 3.7 log10 IU/mL in the 50 mg QD arm, 3.2 log10 IU/mL in the 50 mg BID arm and 3.5 log10 IU/mL in the 100 mg QD arm.

· In genotype 2 patients (n=8), the mean maximal viral load reduction was 2.0 log10 IU/mL in both the 50 mg BID and 100 mg QD dose arms with a greater variability in responses among these patients (range: 0.3 - 4.1 log10 IU/mL). The company is currently conducting pharmacokinetic and sequencing analyses to further characterize these results.

· In genotype 3 patients (n=8), mean maximal viral load reductions were 3.3 log10 IU/mL in the 50 mg BID arm and 3.4 log10 IU/mL in the 100 mg QD arm.

· In genotype 4 patients (n=7), mean maximal viral load reductions were 3.9 log10 IU/mL in the 50 mg BID dose arm and 3.4 log10 IU/mL in the 100 mg QD dose arm.

More detailed findings are expected to be presented at a scientific meeting in the second half of 2012.

"We are pleased to demonstrate the first clinical validation of IDX719 in patients in a multiple-dose study with robust activity across multiple HCV genotypes," commented Douglas Mayers, M.D., Chief Medical Officer of Idenix. "Given these promising findings, we look forward to initiating a phase II combination study of IDX719 with IDX184 by the end of this year."


IDX184 is an unpartnered, novel, liver-targeted nucleotide prodrug of 2'-methyl guanosine, which includes Idenix's proprietary liver-targeting technology. This technology enables the delivery of nucleoside monophosphate to the liver, leading to the formation of high levels of nucleoside triphosphate, potentially maximizing drug efficacy and limiting systemic side effects with low, once-daily dosing. In the ongoing phase IIb clinical trial, IDX184 has been well tolerated with a side effect profile similar to that of PegIFN/RBV. In the first cohort of 31 patients, at 12 weeks in an intent-to-treat analysis, the complete early virologic response ( < 25 IU/mL at 12 weeks) was 93% for the 100 mg IDX184 arm (n=15) and 81% for the 50 mg IDX184 arm (n=16) of the study. The company completed enrollment of a second cohort of 36 additional patients in May 2012.


IDX719 is an NS5A inhibitor with low picomolar, pan-genotypic antiviral activity in vitro. In 36 healthy volunteers, IDX719 was safe and well tolerated at single doses of 5-100 mg as well as multiple doses of 100 mg for 7 days. Single doses of IDX719 demonstrated potent pan-genotypic antiviral activity in 18 genotype 1, 2 or 3 HCV-infected patients, with greater than 3 log10 viral load reductions achieved in the 100 mg dose arm.

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