Date: 2014-01-13
Type of information:
phase: 2
Announcement: interim results
Company: Medivir (Sweden) Janssen Pharmaceuticals (J&J - USA) Idenix Pharmaceuticals (USA)
Product: simeprevir (TMC435), samatasvir (IDX719), TMC647055
Action
mechanism: Samatasvir (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). 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.
TMC647055 is a 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. Medivir and Janssen have recently announced that simeprevir (TMC435) and TMC647055, have entered a phase IIa interferon free combination trial.
Simeprevir (TMC435) is a once daily 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).
Disease: hepatitis C
Therapeutic area: Infectious diseases
Country:
Trial
details: * The HELIX-1 trial is a 12-week, randomized, double-blind, parallel group study evaluating the safety and tolerability of simeprevir and samatasvir in addition to antiviral activity endpoints, with a target enrollment of 90 treatment-naïve, non-cirrhotic, genotype 1b or 4 HCV-infected patients. Patients in part A of the study (n=63) were enrolled in one of three treatment groups receiving 50, 100, or 150 mg samatasvir once-daily for 12 weeks in combination with 150 mg of simeprevir plus a weight-based dose of ribavirin. In part B of the ongoing HELIX-1 study, exploratory cohorts of patients have been added to evaluate the safety and antiviral activity of a 25 mg dose of samatasvir in genotype 1b-infected patients and of a 100 mg dose of samatasvir in genotype 6-infected patients.
* A second phase II trial (HELIX-2) was initiated in December 2013 evaluating samatasvir, simeprevir and TMC647055, a once-daily non-nucleoside polymerase inhibitor plus a low-dose ritonavir being developed by Janssen, with and without ribarivin in genotype 1-infected patients who are either treatment-naïve or have previously relapsed after treatment with pegylated interferon and ribavirin.
Latest
news: * On January 13, 2014, Medivir and Idenix Pharmaceuticals have released interim data from the ongoing phase II HELIX-1 clinical trial evaluating an all-oral, direct-acting antiviral (DAA) HCV combination regimen of samatasvir (IDX719), Idenix’s once-daily pan-genotypic NS5A inhibitor, and simeprevir , a once-daily protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB, and ribavirin.
The combination regimen of the study was well-tolerated. In the treatment-naïve, non-cirrhotic, genotype 1b or 4 HCV-infected patients receiving 50 mg of samatasvir and 150 mg of simeprevir plus ribavirin for 12 weeks, 85 percent (n=17/20) of the patients achieved SVR4 (undetectable HCV RNA four weeks after end of treatment). The 50 mg dose of samatasvir is the selected dose in the ongoing 3-DAA HELIX-2 clinical trial. The HELIX-1 study results are expected to be presented at a scientific meeting in 2014.
* On May 30, 2013, Medivir has announced that Idenix Pharmaceuticals has initiated a phase II clinical trial, called HELIX-1, evaluating an all-oral, direct-acting antiviral (DAA) HCV combination regimen of simeprevir, and samatasvir (IDX719). The HELIX-1 trial is the first study in HCV-infected patients to commence under a non-exclusive collaboration agreement signed between Janssen and Idenix in January 2013. A second trial (HELIX-2) of simeprevir, samatasvir and TMC647055, a once-daily non-nucleoside polymerase inhibitor boosted with low-dose ritonavir being developed by Janssen, is expected to commence in the second half of 2013.
* On January 28, 2013, Medivir has announced a non-exclusive collaboration between Janssen Pharmaceuticals 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.
Simeprevir is being investigated in combination with PegIFN/RBV in phase III trials and is also being evaluated with 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.
