PSI-7977
PSI-7977
PSI-7977 is an investigational nucleotide analog currently in Phase 2 for treatment of chronic HCV infection. PSI-7851 is a mixture of two similar molecules, PSI-7976 and PSI-7977, which exist in PSI-7851 as isomers of each other. Once inside a liver cell, both molecules are rapidly converted to the same active triphosphate. Given the ability to more easily manufacture PSI-7977, and potentially advantageous in vitro characteristics, PSI-7977 was selected for further clinical development.
Phase 2b Studies
In March 2011, Pharmasset began screening a Phase 2b study evaluating PSI-7977 in combination with pegylated interferon alfa-2a and ribavirin called ATOMIC. This Phase 2b trial is planned to enroll approximately 300 patients with chronic HCV genotype 1 who have not been treated previously. The primary endpoint of the trial will be the safety and tolerability of PSI-7977 400mg QD in combination with peginterferon and ribavirin over 12 or 24 weeks. The trial will be conducted in the U.S. Patients will be randomized (1:2:3) into the following arms.
HCV GT1 patients will be stratified by IL28B status and baseline HCV RNA to ensure balance across cohorts. An additional 25 treatment-nave patients with HCV genotype 4, 5, 6 or indeterminate genotype, will receive PSI-7977 400mg QD with peginterferon and ribavirin for 24 weeks.
In August 2010, Pharmasset began a Phase 2b study evaluating PSI-7977 in combination with pegylated interferon alfa-2a (Peg-IFN) and ribavirin (RBV) called PROTON. This study compares PSI-7977 200mg QD, 400mg QD, or placebo in combination with Peg-IFN/RBV in approximately 125 treatment-nave non-cirrhotic patients with HCV genotype 1.
The primary goal of the study is to assess the safety and tolerability of PSI-7977 in combination with Peg-IFN/RBV for 12 weeks. The primary efficacy endpoint of the study is the proportion of patients who achieve an SVR12 and SVR24, defined as HCV RNA below the limit of detection (<15 IU/ml) 12 and 24 weeks, respectively, after the discontinuation of all therapy.
Patients will receive PSI-7977 in combination with Peg-IFN/RBV for 12 weeks, followed by an additional 12 weeks of PegIFN/RBV if their HCV RNA is below the limit of detection at week 4 through week 12; otherwise, patients will continue on Peg-IFN/RBV through week 48. All patients randomized to placebo/ Peg-IFN/RBV will receive a total of 48 weeks of therapy.
We expect to report interim results from the first 12 weeks of treatment for HCV GT1 during the second quarter of calendar year 2011.
In a fourth, open label arm of the PROTON study, we enrolled 25 treatment-nave patients with HCV genotype 2 or 3. These 25 treatment-nave patients are receiving PSI-7977 400mg QD with Peg-IFN/RBV for 12 weeks with no Peg-IFN/RBV follow-up. Patients will be monitored for an additional 24 weeks after discontinuation of therapy to assess SVR at 12 weeks and 24 weeks.
We expect to report preliminary 12 week safety results from this open label arm during the first quarter of calendar year 2011 and to report SVR12 from this arm during the second quarter of calendar year 2011. We also expect to initiate a 24-week Phase 2b study of PSI-7977 in combination with Peg-IFN/RBV during the second calendar quarter of 2011.
In December 2010, we initiated a Phase 2b ELECTRON study of PSI-7977 in combination with ribavirin (RBV) administered with and without pegylated interferon alfa-2a (Peg-IFN). The study is expected to enroll approximately 40 treatment-nave patients with HCV genotype 2 or 3 and is designed to assess SVR with 12 weeks of PSI-7977/RBV (no IFN) and with different, limited durations of treatment with Peg-IFN.
We expect to report interim results from the ELECTRON trial during the second half of calendar year 2011.
Phase 2a Study
During May 2010, we announced efficacy and preliminary safety results from the 28 day phase 2a study with PSI-7977 dosed once daily (QD) in combination with Pegasys(R) (peginterferon alfa-2a) and Copegus(R) (ribavirin), the current standard of care (SOC) in patients with hepatitis C virus (HCV) genotype 1 who were nave to antiviral therapy.
The primary efficacy endpoint of the trial was the proportion of patients who achieved a rapid virologic response (RVR), defined as HCV RNA below the limit of detection (<15 IU/mL as measured by the TaqMan assay) four weeks after the initiation of treatment. Following 28 days of combination therapy, patients will receive a further 44 weeks of SOC and will be followed through a Sustained Virologic Response (SVR) endpoint.
Potent and consistent antiviral activity was demonstrated in this study following 28 days of treatment with PSI-7977 in combinatio
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