Locteron Phase 2b Clinical Results

Interim results from three Phase 2b studies were the subject of three presentations at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria. Each study achieved our objective by demonstrating viral kinetics and response rates that were comparable to the standard of care while also achieving up to a 65% reduction in flu-like adverse events.

SELECT-2 Phase 2b Trial
The SELECT-2 Phase 2b trial is being conducted in the United States and Europe in 116 treatment-naïve, genotype-1, chronic hepatitis C patients. Patients were randomized into one of four dosing cohorts, the 320, 480 or 640 µg dose of Locteron (administered once every two weeks) or a control arm consisting of PEG-Intron (1.5 µg/kg, administered every week), with all patients receiving weight-based ribavirin. Patients will be treated for 48 weeks and will be followed for an additional 24 weeks to determine the sustained virologic response (SVR) rate. All patients in the trial have completed at least 36 weeks of study.

Through 36 weeks of treatment in SELECT-2, Locteron administered once every two weeks in the 640 and 480 µg dose cohorts demonstrated reductions in viral loads (mean changes in HCV RNA from baseline) that were comparable to that achieved with PEG-Intron administered once per week. Although the reduction in mean HCV RNA for the 320 µg dose of Locteron were comparable to PEG-Intron after 36 weeks of treatment, patients treated with this lower dose of Locteron demonstrated a slower viral kinetics (compared to the Locteron 480 and 640 µg doses and PEG-Intron) at earlier time points.

In SELECT-2, flu-like adverse events were predefined to include arthralgia, chills, fever, headache, and myalgia. A substantial reduction in flu-like adverse events for patients treated with Locteron was evident even in the first week of the trial and continued through the 36-week time point available for evaluation. Under the statistical analysis plan for the trial, the reductions in flu-like adverse events were tested after four and 12 weeks of treatment and were statistically significant for all three Locteron doses. After 36 weeks of treatment, total flu-like adverse events reported in each of the three Locteron cohorts were 35% of the total events reported in the PEG-Intron control group, a 65% reduction.

EMPOWER Phase 2b Study
In the EMPOWER study, the 480 µg dose of Locteron demonstrated viral kinetics and response rates that were comparable to the PEG-Intron® control while also achieving a 57% reduction in flu-like adverse events.

The objective of the EMPOWER study was to test the hypothesis that the 480 ug dose of Locteron dosed once every two weeks reduces flu-like symptoms but retains equivalent efficacy compared to PEG-Intron (1.5 µg/kg, administered every week). All patients were also treated with weight-based ribavirin. The 133 patients in the EMPOWER study were enrolled in two contributing Phase 2b trials (SELECT-2 and the 480 STUDY). All patients were treatment-naïve-genotype-1 subjects with chronic hepatitis C. A total of 30 sites participated in the two trials (14 sites in the US, 11 in Europe, and five in Israel). All patients in EMPOWER have completed at least six weeks of study, and over 80% of the patients have completed 12 weeks of study.

Through six weeks of treatment, Locteron 480 µg administered once every two weeks demonstrated reductions in viral loads (mean changes in HCV RNA from baseline) that were somewhat more rapid than that achieved with PEG-Intron administered once per week. Rates of undetectable HCV RNA achieved after six weeks of treatment were 31% for Locteron 480 µg and 19% for PEG-Intron. The currently available results after 12 weeks of treatment (a number of patients have not yet reached the 12-week time point) suggest comparable reductions in mean HCV RNA and rates of undetectable HCV RNA for Locteron 480 µg and PEG-Intron.

In EMPOWER, flu-like adverse events were predefined to include arthralgia, chills, fever, headache, and myalgia. A substantial reduction in flu-like adverse events for patients treated with Locteron was evident even in the first week of the trial and continued through the 12-week time point available for evaluation. After six weeks of treatment, total flu-like adverse events reported for Locteron 480 µg were 52% less than the total events reported for PEG-Intron. Available results after 12 weeks of treatment suggest total flu-like adverse events reported for Locteron 480 µg were 57% less than the total reported for PEG-Intron.

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