Samatasvir (IDX719), an NS5A Inhibitor
Idenix’s lead NS5A inhibitor, samatasvir (or IDX719), is in phase II clinical development for all-oral combination treatment of HCV infection. Samatasvir has been shown to have low picomolar, pan-genotypic antiviral activity with high selectivity in vitro. In phase I/II clinical studies, samatasvir demonstrated a positive safety profile and was 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. Further, samatasvir 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 phase I/II monotherapy study. In July 2012, the FDA granted Fast Track designation for samatasvir for the treatment of HCV infection.
In January 2013, Idenix entered into a non-exclusive collaboration with Janssen Pharmaceuticals, Inc. for the clinical development of all-oral direct-acting antiviral (DAA) HCV combination therapies. The collaboration will evaluate combinations including samatasvir, simeprevir (TMC435), a once-daily protease inhibitor jointly developed by Janssen and Medivir AB, and TMC647055, a once-daily non-nucleoside polymerase inhibitor, boosted with low dose ritonavir, being developed by Janssen.
In May 2013, Idenix initiated the phase II HELIX-1 clinical trial evaluating the all-oral combination of samatasvir and simeprevir plus ribavirin. The HELIX-1 trial is a 12-week, randomized, double-blind, parallel-group study evaluating the safety, tolerability and antiviral activity of the combination regimen in treatment-naïve, non-cirrhotic, genotype (GT) 1b or 4 HCV-infected patients. In Part A, patients are randomized equally across three treatment arms, receiving either 50, 100, or 150 mg samatasvir once-daily for 12 weeks in combination with simeprevir plus ribavirin. Part B includes exploratory cohorts that have been added to evaluate a 25 mg dose of samatasvir in combination with simeprevir and ribavirin in GT 1b-infected patients and a 100 mg dose of samatasvir in combination with simeprevir and ribavirin in GT 6-infected patients. All patients have completed enrollment in Part A, and SVR4 data for these patients are anticipated late in the fourth quarter of 2013.
Idenix is planning to initiate a second trial (HELIX-2) of samatasvir, simeprevir and TMC647055. The HELIX clinical trials will be conducted by Idenix. Janssen and Idenix retain all rights to their respective compounds under this agreement.
Novel Nucleotide Prodrug Discovery Program
Idenix maintains robust R&D programs to identify and develop next-generation nucleotide polymerase prodrug inhibitors for HCV, leveraging the Company’s significant nucleotide chemistry expertise as well as its strong intellectual property position.
IDX21437, a next-generation uridine nucleotide prodrug inhibitor, has received approval to enter clinical trials in Canada and Belgium. Idenix has initiated the healthy volunteer portion of a phase I/II clinical trial. Extensive preclinical testing for IDX21437 demonstrated favorable antiviral activity across genotypes 1-6 and a safety profile which supported advancement into clinical trials.
Idenix is conducting additional preclinical work as requested by the United States Food and Drug Administration for IDX20963, a uridine nucleotide prodrug candidate.
Idenix remains focused on the discovery and development of nucleotides and continues its program to identify new compounds and evaluate multiple candidates for development from this discovery program. The nucleoside discovery capability can also be applied to other therapeutic areas outside of HCV, and the Company looks forward to exploring new indications.
Use of Non-Human Primates (NHPs) in the Discovery and Development of Medicines
“Idenix Pharmaceuticals, Inc. has voluntarily decided to continue its practice of not using great apes in research.”