Locteron, controlled-release interferon alpha 2b, 3 studies at EASL 2010 Vienna

Locteron, controlled-release interferon alpha 2b, 3 studies at EASL 2010 Vienna - 3 company press releases


Company says:

-- Phase 3 ready in 2011

-- Locteron incorporates PolyActive, a controlled-release technology, which provides a gradual release of interferon alpha to patients without the high initial blood levels associated with the significant side effects experienced by patients today.

-- Locteron is also formulated to allow dosing once every two weeks

BIOLEX ANNOUNCES PRESENTATION AT EASL OF INTERIM RESULTS FROM 480 STUDY, A PHASE2b TRIAL OF LOCTERON® IN CHRONIC HEPATITIS C Phase 2b Results in Oral Presentation at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria -

PITTSBORO, NORTH CAROLINA, April 19, 2010 - Biolex Therapeutics, Inc. announced that interim results from a Phase 2b trial of Locteron®, the "480 STUDY," were presented Friday evening at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria. Locteron, controlled-release interferon alpha 2b, is designed to improve patient care by providing a more convenient once-every-two week dosing schedule and by reducing the flu-like symptoms associated with pegylated interferons, the current standard of care. Through six and 12 weeks of treatment in the trial, Locteron achieved the Company's objective by demonstrating viral kinetics and response rates that were at least comparable to the PEG-Intron® control while also achieving a reduction in flu- like adverse events.

The Phase 2b trial is being conducted in Europe and Israel and includes 74 treatment-naïve hepatitis C patients with the genotype-1 variant of the virus. The 480 STUDY is designed to provide, in combination with the SELECT-2 Phase 2b trial, patient results for use in the EMPOWER analyses of efficacy and tolerability of the 480 µg dose of Locteron versus PEG- Intron (interim results from SELECT-2 and EMPOWER were also presented at the EASL conference last week). The 480 STUDY includes the first clinical evaluation of the single- injection drug configuration of Locteron planned for use in Phase 3 trials.

In Panel A of the 480 STUDY, 42 patients were randomized in Europe to receive treatment with either the 480 µg dose of Locteron (in the same two-injection configuration as the SELECT-2 trial) or PEG-Intron. In Panel B, 32 patients in Israel were randomized to receive treatment with either the 480 µg dose of Locteron (single-injection format) or PEG-Intron. Participants in the 480 STUDY are treatment-naïve, genotype-1, chronic hepatitis C patients, and all participants also received weight-based ribavirin. All patients in Panel A of the trial have completed 12 weeks of study and all patients in Panel B have completed at least six weeks of study.

In both Panel A and Panel B, the Locteron 480 µg dose administered once every two weeks demonstrated reductions in viral loads (mean changes in HCV RNA from baseline) that were at least comparable to that achieved with PEG-Intron administered once per week. Rates of undetectable HCV RNA achieved in each Panel and on a combined basis are outlined in the table below:


In the 480 STUDY, flu-like adverse events were predefined to include arthralgia, chills, fever, headache, and myalgia. After six weeks of treatment, total flu-like adverse events reported for Locteron 480 µg for Panel A and Panel B combined 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 58% less than the total reported for PEG- Intron. The majority of the difference occurred in Panel A as the flu-like adverse events reported in Panel B, which is still in process, were low in both cohorts.

The 480 STUDY results were presented by the lead author, Zahariy Krastev, MD, Principal Investigator, University Hospital "St Ivan Rilski," Sofia, Bulgaria, in an oral presentation titled "Randomized, Open-Label, 12-Week Comparison of Controlled-Release Interferon Alpha2b + Ribavirin Vs. Pegylated-Interferon Alpha2b + Ribavirin in Treatment-Naïve Genotype1 Hepatitis C: 4 Week Results from 480 STUDY (Panel A)."

"We are pleased that the efficacy of Locteron in these interim results is at least comparable to PEG-Intron despite the fact that Locteron was dosed half as frequently," said Dr. Krastev. "There is a need for a more convenient and more tolerable interferon component of hepatitis C therapy, particularly with the advent of triple-combination therapy, and I look forward to participating in expanded trials of Locteron in the future."

One serious adverse event has been reported to date for Locteron 480 µg and three were reported for PEG-Intron. All events were expected labeled events for interferon alpha. No Grade 4 reductions in hematological measurements have been reported to date for either Locteron 480 µg or for PEG-Intron. There were no novel toxicities identified in either cohort of the trial.

BIOLEX ANNOUNCES PRESENTATION AT EASL OF INTERIM RESULTS FROM EMPOWER PHASE 2b STUDY OF LOCTERON® IN CHRONIC HEPATITIS C

Locteron dosed once every two weeks demonstrated a comparable reduction in viral load compared to once-weekly standard of care with 57% less flu-like adverse events

PITTSBORO, NORTH CAROLINA, April 16, 2010 - Biolex Therapeutics, Inc. announced that interim results from EMPOWER, a prospectively designed analysis of results from two Phase 2b trials of Locteron®, were presented yesterday in a late-breaker session at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria. Locteron, controlled-release interferon alpha 2b, is designed to improve patient care by providing a more convenient once-every-two week dosing schedule and by reducing the flu-like symptoms associated with pegylated interferons, the current standard of care. 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). The 133 patients in the EMPOWER study were enrolled in two contributing Phase 2b trials:

· SELECT-2, a Phase 2b dose-finding trial evaluating the 320, 480 or 640 µg doses of Locteron versus PEG-Intron. Interim results from SELECT-2 were also presented at EASL yesterday. SELECT-2 contributed a total of 59 Locteron 480 µg and PEGIntron patients to EMPOWER.

· The 480 STUDY, a Phase 2b trial evaluating the 480 µg dose of Locteron versus PEGIntron. Interim results from the 480 STUDY will be presented in an oral presentation at EASL later today. The 480 STUDY contributed 74 patients to EMPOWER.

All patients were treatment-naïve-genotype-1 subjects with chronic hepatitis C, and all patients were also treated with weight-based ribavirin. 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 PEGIntron.

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.

The EMPOWER results were presented by the lead author, Walker Long, MD, Chief Medical Officer and Vice President, Drug Development, Biolex Therapeutics, in the form of a poster titled "Q2Week Controlled-Release Interferon Alpha2b + Ribavirin Reduces Flu-like Symptoms >50% and Provides Equivalent Efficacy in Comparison to Weekly Pegylated Interferon Alpha2b + Ribavirin in Treatment-Naïve Genotype 1 Chronic Hepatitis C: Results from EMPOWER, a Randomized Open-Label 12-week Comparison in 133 Patients."

"The EMPOWER study allows us to focus on the activity associated with one specific dose of Locteron and test our hypothesis that equivalent efficacy can be achieved while greatly reducing flu-like adverse events," said Dr. Long. "These results exceed our expectations. We believe that the importance of reducing flu-like adverse events will grow with the advent of direct-acting virals and the shortening of therapy, due to the prevalence of these side effects during the first three months of treatment."

Three serious adverse events were reported for Locteron 480 µg and three were reported for PEG-Intron. All events were expected labeled events for interferon alpha. Higher rates of mild or moderate (Grade 2 and Grade 3) reductions in measurements of white blood cell counts, platelets and neutrophils were observed for Locteron 480 µg compared to PEG-Intron, while higher rates of mild or moderate reductions in measurements of hemoglobin were observed for PEG-Intron. There were no Grade 4 reductions in hematological measurements for either Locteron 480 µg or for PEG-Intron. There were no novel toxicities identified in either cohort of the trial.

BIOLEX ANNOUNCES PRESENTATION AT EASL OF INTERIM RESULTS FROM SELECT-2 PHASE2b TRIAL OF LOCTERON® IN CHRONIC HEPATITIS C

Locteron dosed once-every-two-weeks demonstrated a comparable reduction in viral load compared to once-weekly standard of care with a 65% reduction in flu-like adverse events

PITTSBORO, NORTH CAROLINA, April 15, 2010 - Biolex Therapeutics, Inc. announced that interim results from its SELECT-2 Phase 2b dose-finding trial of Locteron® are being presented today at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria. Locteron, controlled-release interferon alpha 2b, is designed to improve patient care by providing a more convenient once-every-two week dosing schedule and by reducing the flu-like symptoms associated with pegylated interferons, the current standard of care. Through 36 weeks of treatment in the trial, Locteron achieved the Company's objective by demonstrating viral kinetics and response rates that were comparable to the PEGIntron® control while also achieving a 65% reduction in flu-like adverse events.

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.

Rates of undetectable HCV RNA achieved in each cohort are outlined in the table below:


A substantial proportion of patients treated with interferon experience flu-like adverse events, particularly during the first three months of treatment. Market research shows that flu-like symptoms are associated with hesitation to initiate therapy, lack of adherence during therapy, and significant discomfort and dissatisfaction with the current standard of care. A major objective of the SELECT-2 trial was to further test the hypothesis that Locteron's controlledrelease mechanism would reduce the flu-like adverse events experienced by patients.

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. The percentage reduction in total flu-like adverse events reported for each cohort of Locteron versus those reported for PEG-Intron are summarized in the table below:


The SELECT-2 results were presented by the lead author, Eric Lawitz, MD, Medical Director and Principal Investigator, Alamo Medical Research, in the form of a poster titled "Early Viral Response of Controlled-Release Interferon Alpha2b and Ribavirin vs. Pegylated-Interferon Alpha2b and Ribavirin in Treatment-Naïve Genotype-1 Hepatitis C: 12 Week Results (Select-2 Trial)."

"The interim results from the SELECT-2 trial are certainly consistent with the promise of this drug candidate," said Dr. Lawitz. "I look forward to seeing the development of Locteron expanded to larger trials and to testing in combination with direct-acting anti-viral agents."

Total serious adverse events reported for Locteron 640, 480 and 320 µg doses, and for PEG-Intron, were two, two, four and one, respectively. All serious adverse events were expected and consistent with labeled events for interferon alpha. Higher rates of mild or moderate (Grade 2 and Grade 3) reductions in hematological measurements (white blood cell counts, platelets, hemoglobin, and neutrophils) were observed on the 640 and 480 µg doses of Locteron in comparison to PEG-Intron but did not lead to higher rates of discontinuation or lower rates of viral response. There were no Grade 4 reductions in hematological measurements in any of the Locteron doses, and only one Grade 4 reduction in the PEG-Intron arm (one neutrophil count <500). There were no novel toxicities identified in any cohort of the trial.

Locteron is an investigational therapeutic candidate and has not been approved for sale by the United States Food and Drug Administration or by any international regulatory agency.