SOURCE: Biolex Therapeutics

Biolex Therapeutics

April 15, 2010 02:01 ET

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, NC--(Marketwire - 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 PEG-Intron® 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:

SELECT-2 Interim Results  
% of Patients with Undetectable HCV RNA  
  640 µg   480 µg   320 µg   PEG-Intron  
  (n=29)   (n=29)   (n=28)   (n=30)  
12 Weeks 41 % 38 % 39 % 40 %
36 Weeks 52 % 41 % 46 % 50 %

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 controlled-release 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:

SELECT-2 Interim Results  
Reduction in Flu-Like Adverse Events Compared to PEG-Intron Control  
  640 µg   480 µg   320 µg  
Through 12 Weeks 53 % 55 % 59 %
  p < 0.001   p < 0.001   p < 0.001  
Through 36 Weeks 65 % 65 % 65 %

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.

Locteron Overview
Locteron is a controlled-release interferon alpha designed to improve patient care in the treatment of hepatitis C through a more favorable side-effect profile and dosing convenience compared to existing pegylated interferon products. In contrast to Locteron's controlled-release mechanism, the currently approved products, Pegasys® and PEG-Intron, and the investigational product Zalbin™, are immediate-release products that lack a controlled-release mechanism. Interferon alpha serves as the foundation of current combination therapy for hepatitis C patients. It is estimated that worldwide sales of interferon products for the treatment of hepatitis C will approach $6 billion by 2016.

Locteron incorporates an advanced controlled-release drug delivery technology that allows dosing once every two weeks, more convenient than Pegasys and PEG-Intron, each of which require dosing every week. More importantly, Locteron's controlled-release mechanism results in the gradual release of interferon alpha 2b to patients over the duration of two weeks and avoids the early peak plasma levels of the active interferon that characterize the pegylated interferons and Zalbin. This controlled-release mechanism is designed to reduce the frequency, duration and severity of flu-like symptoms commonly experienced by patients treated with pegylated interferons and with Zalbin. 

About Biolex Therapeutics
Biolex is a biopharmaceutical company that uses its patented LEX System(SM) to develop follow-on biologics, hard-to-make therapeutic proteins and to optimize monoclonal antibodies. The LEX System is a novel technology that genetically transforms the aquatic plant Lemna to enable the production of biologic product candidates. The company's product candidates are designed to provide superior efficacy/tolerability profiles and to address large, proven pharmaceutical markets. Biolex's lead product candidate, Locteron®, is in Phase 2b clinical testing for the treatment of chronic hepatitis C. Biolex has also developed two other product candidates that capitalize on the benefits of the LEX System. BLX-301 is a humanized anti-CD20 antibody glyco-optimized for the treatment of non-Hodgkin's B-cell lymphoma and other diseases. BLX-155 is a direct-acting thrombolytic designed to dissolve blood clots in patients.

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