PITTSBORO, NC -- 07/26/07 --
Biolex Therapeutics today announced
successful initial results from the SELECT-1 Phase 2a clinical trial of
Locteron(TM), the first controlled-release interferon alfa being developed
for the treatment of chronic hepatitis C. In the 12-week Phase 2a trial,
the combination of the highest dose of Locteron evaluated and the antiviral
drug ribavirin achieved an early virologic response (EVR) in 100% of the
hepatitis C patients treated. Importantly, the study results also
indicated that patients receiving Locteron experienced side effects that
were less frequent and less severe than those previously reported in
clinical trials for the currently marketed pegylated interferons and for
albumin-fused interferon (Albuferon(TM)) currently under development.
Biolex is co-developing Locteron with its partner OctoPlus N.V.
SELECT-1 (Safety and Efficacy of Locteron: European Clinical Trial-1) was
designed to evaluate a range of up to four doses of Locteron administered
once every two weeks in combination with ribavirin in a total of 32
treatment-naïve hepatitis C patients with the genotype-1 variant of the
virus. The SELECT-1 protocol calls for patients to be treated for 12 weeks
with the Locteron/ribavirin combination, and the repeat-dose study will
assess viral response, safety and tolerability for each dose cohort. Under
the protocol, dosing was commenced in January 2007 for the first three
eight-patient cohorts of the study, the 160, 320 and 480 microgram (µg)
doses, and dosing of the 640 µg cohort was to be triggered based on an
assessment of safety and tolerability for the first three dose cohorts. As
a result of a favorable safety and tolerability review for the first three
dose cohorts, dosing of patients in the 640 µg cohort commenced in May 2007
and results are expected to be available in the fourth quarter of 2007.
"We are very pleased with the results from SELECT-1 as they support our
original hypothesis for Locteron, that a controlled-release interferon alfa
has the potential to provide a high level of efficacy while resulting in an
improvement in side effects and patient tolerability," said Mr. Jan Turek,
Biolex President and Chief Executive Officer. "Even in advance of
completion of the highest-dose cohort in the study, SELECT-1 has
highlighted two doses that appear to provide a combination of efficacy and
improved tolerability. We believe that the need for improved patient
tolerability will become even greater with the emergence of new antiviral
products. These emerging antiviral products are associated with additional
side effects, further adding to the potential for Locteron to be the
interferon of choice for future combination therapy as a result of its
potential for improved patient tolerability."
SELECT-1 Antiviral Results
The study has been completed for the 160, 320 and 480 µg dose cohorts of
the study. The 12-week antiviral results for the two Locteron doses that
were most effective, the 320 and 480 µg doses, compare favorably with
results previously reported in clinical trials for the currently marketed
pegylated interferon alfa products and for Albuferon. At the conclusion of
the study, 12 weeks of treatment, the results for the 160, 320 and 480 µg
dose cohorts were as follows:
-- A dose response was observed in the study, with patients treated with
the 320 and 480 µg doses of Locteron demonstrating a greater reduction in
hepatitis C virus than the patients treated with the 160 µg dose at all
measurement times. Average viral reduction after 12 weeks of treatment for
the 320 and 480 µg doses was 4.5 and 4.2 logs, respectively, compared to
1.8 logs in the lowest dose of 160 µg.
-- After 12 weeks of treatment, plasma hepatitis C RNA was reduced to
undetectable levels ( < 28 IU/ml) in 63% (5/8) and 63% (5/8) of the
patients in the 320 and 480 µg dose cohorts, respectively, compared to 13%
(1/8) of the patients in the lowest-dose group of 160 µg.
-- The percentage of patients who achieved early virologic response
(EVR), defined as at least a two-log reduction in hepatitis C virus after
12 weeks of treatment, was 88% (7/8) and 100% (8/8) in the 320 and 480 µg
dose cohorts, respectively, compared to 38% (3/8) of the patients in the
lowest-dose group of 160 µg. Achievement of EVR has been broadly
established to be a pre-requisite for long-term response.
SELECT-1 Safety and Tolerability Results
The following Locteron side effect and patient tolerability results were
observed during the 12 weeks of treatment for the 160, 320 and 480 µg dose
cohorts:
-- Locteron was safe and well tolerated.
-- There were no serious adverse events.
-- The vast majority (over 90%) of the adverse events that were
experienced were rated as mild.
-- Dose reductions were limited to one patient each in the 320 and 480 µg
dose cohorts with none in the 160 µg dose cohort.
-- No patients discontinued treatment.
The majority of the side effects experienced by patients treated with
Locteron in the SELECT-1 study in the 160, 320 and 480 µg dose cohorts
appear to be less frequent and less severe than the side effects reported
in previous clinical trials for pegylated interferons and Albuferon. For
example, only one patient in the SELECT-1 study receiving Locteron
experienced an adverse event rated as severe, indicating an improvement
over previously reported results in clinical trials for Pegasys® and
Albuferon as illustrated in Figure 1.
Although many of the side effects experienced by patients in the SELECT-1
trial and clinical trials for other interferon products are subjective in
nature, the occurrence of fever is an objective point of comparison and is
a marker for the family of adverse events characterized as flu-like
symptoms and. Fever, characterized by a temperature reading of at least 38
degreesC, occurred in only one (4%) of the Locteron patients in SELECT-1,
notably lower than other interferon products as illustrated in Figure 2.
Furthermore, the rates of other side effects previously reported in
clinical trials for pegylated interferons and Albuferon, such as chills,
diarrhea, dizziness, headache, irritability, and nausea, also appeared to
be lower in patients treated with Locteron in SELECT-1. All other side
effects experienced by patients treated with Locteron in SECLECT-1 were
predominantly mild and appeared as a group to be comparable with other
interferon products.
Locteron Overview
Locteron combines BLX-883, a recombinant interferon alfa produced by Biolex
in its patented LEX System(SM), with PolyActive(TM), an advanced
controlled-release drug delivery technology developed by OctoPlus.
Locteron is the first controlled-release interferon alfa under clinical
development for the treatment of hepatitis C and is designed to improve
patient care through a more favorable side-effect profile and more
convenient patient dosing. Locteron is configured to allow dosing once
every two weeks, an improvement in patient convenience compared to
currently marketed pegylated interferon alfa products that require dosing
every week. More importantly, Locteron's controlled-release mechanism
results in the gradual release of interferon alfa to patients over the
duration of two weeks. This controlled-release mechanism is designed to
cover inter-dose troughs while reducing the frequency, duration and
severity of side effects, including flu-like symptoms, commonly experienced
by patients treated with currently marketed pegylated interferons and with
Albuferon.
Biolex and OctoPlus plan to commence SELECT-2, a Phase 2b trial of Locteron
in 2008 after assessment of the final results from the SELECT-1 Phase 2a
trial, expected to occur in the fourth quarter of 2007. The 12-week
results of the Phase 2b trial will be used as the basis for dose selection
for the commencement of the Phase 3 development program.
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.
About Biolex Therapeutics
Biolex Therapeutics is developing and commercializing therapeutic proteins
based on its proprietary LEX System(SM), an expression system that enables
the commercially viable production of hard-to-make proteins and the
optimization of monoclonal antibodies. The Company is developing a
proprietary pipeline of biologic product candidates that have known
mechanisms of action and have the potential to provide a reduced risk
profile while targeting large, proven pharmaceutical markets. Biolex's lead
candidate, Locteron(TM), under joint development with OctoPlus N.V., is in
Phase 2 clinical development as a controlled-release interferon alfa for
the treatment of hepatitis C. The Company's second product candidate,
BLX-155, is a direct-acting thrombolytic, designed to break up blood clots
in patients with diseases or conditions such as acute peripheral arterial
disease, deep vein thrombosis and hemodialysis graft thrombosis. In
addition, the potential capabilities of the LEX System has led to
collaborations with Centocor, Medarex, Genmab and other leading
pharmaceutical and biotech companies. Biolex is a venture capital-backed
company located in the Research Triangle region of North Carolina, United
States. For additional information, please visit Biolex's web site at
www.biolex.com.
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