Galectin Therapeutics (Nasdaq:GALT), the leading developer of
therapeutics that target galectin proteins to treat fibrosis and
cancer, announces that final results from its Phase 1 trial show
that GR-MD-02 had an effect on a serum biomarker (as assessed by
FibroTest®) and liver stiffness (as assessed by FibroScan®) that
suggest a potential for therapeutic effect on fibrosis that
warrants further exploration. This first-in-man study, which
enrolled 30 patients in three cohorts, principally evaluated the
safety, tolerability and pharmacokinetics for single and multiple
doses of its galectin-inhibiting drug GR-MD-02 when administered
intravenously to patients with fatty liver disease, or nonalcoholic
steatohepatitis (NASH) with advanced fibrosis. The study also
secondarily examined exploratory biomarkers as well as a newer
non-invasive liver stiffness measure. Final Phase 1 data are
included in a new corporate presentation which is available on the
Company's website (www.galectintherapeutics.com).
GR-MD-02 administered to patients in three cohorts in doses up
to 8 mg/kg for a total of four doses was found to be safe and
well-tolerated. There were no serious adverse events or
treatment-emergent adverse events attributed to the study drug.
Mild (grade 1) adverse events possibly attributable to drug were
identified in more patients receiving placebo (4 patients) than
those receiving active drug (2 patients). The pharmacokinetic
analysis of GR-MD-02 plasma levels for the 8 mg/kg dose shows that
plasma drug coverage was in the upper portion of the targeted
therapeutic range derived from NASH animal model studies.
Therefore, the highest dose in the third cohort suggested a desired
dose for testing in Phase 2 clinical trials.
"The final conclusion of the Phase 1 trial is that GR-MD-02 is
safe and well tolerated after multiple doses," said Stephen A.
Harrison, M.D., the lead investigator of the trial and Chief of
Hepatology at Brooke Army Medical Center in Fort Sam Houston.
"Additionally, the highest dose utilized is within the therapeutic
range, and had significant effects on a relevant biomarker of
fibrotic liver disease and a potential signal indicating a
reduction in liver stiffness. These findings provide a firm
foundation for a Phase 2 clinical trial program and I am
enthusiastic about participating in these trials." Dr. Harrison
also presented interim results of the study at the 2014 AASLD
annual meeting, where he represented a group of principal
investigators from leading medical institutions in the U.S., many
of whom have authored seminal publications on liver disease and
NASH in particular.
Evaluation of FibroTest®, a biomarker consisting of a composite
score of five blood tests that correlates with the extent of liver
fibrosis, showed a statistically significant reduction between
patients administered 8 mg/kg GR-MD-02 and those administered
placebo in cohort 3. In contrast, there was no evidence of a
significant reduction with the doses administered in the first two
cohorts (2 mg/kg and 4 mg/kg), thereby suggesting a dose-dependent
pharmacodynamic effect of GR-MD-02, which will be further explored
in Phase 2 studies. The decrease in FibroTest® score was
attributable to a marked, statistically significant reduction in
serum alpha-2 macroglobulin (A2M), a component of the FibroTest®
score and a serum protein that has been associated with liver
fibrosis. A2M is a relevant marker for liver fibrosis because it
has been shown that serum levels correlate with liver fibrosis.
Moreover, it may be involved in the pathogenesis of fibrosis
because it is known to inhibit proteases such as collagenase, which
may promote fibrosis, and is increased in fibrogenic stellate cells
in liver fibrosis.
Patients in the third cohort were also evaluated for liver
stiffness with FibroScan®, an ultrasound-based instrument approved
by the U.S. Food and Drug Administration (FDA) for use in
non-invasive liver diagnosis. Liver stiffness as measured by
FibroScan® has been shown in multiple studies to correlate with the
degree of liver fibrosis as assessed by liver biopsy. The area of
the liver interrogated with this method is approximately 100-times
larger than the size of a standard liver biopsy. Although not
cleared by the FDA specifically to assess fibrosis, FibroScan® is
believed to represent a promising non-invasive, out-patient method
for measuring changes in liver fibrosis over time without the need
for invasive surgical liver biopsy.
While FibroScan® analysis was added during cohort 2, too few
scans were obtained among those patients for analysis. In cohort 3
there were technically adequate scans at baseline, Day 38 and Day
63 in 5 patients administered GR-MD-02 and 3 patients administered
placebo. Five patients in cohort 3 were not available for
FibroScan® analysis (3 placebo and 2 active) because of
unavailability of the instrument at the site (1 placebo and 1
active), unavailability of the appropriate instrument probe (1
active), a technically inadequate baseline scan (1 placebo) and the
Day 63 scan not being performed (1 placebo). All 3 placebo patients
showed no significant change in FibroScan® scores from baseline to
Day 63, defined as changes of ±20% from baseline. In contrast, 3 of
the 5 patients administered GR-MD-02 showed a reduction in
FibroScan® scores at Day 63 with reductions of 25%, 49% and 53%.
While the number of patients in this analysis is small, these
findings suggest there may be a reduction in liver stiffness with
GR-MD-02 in some patients, which may correlate with the state of
fibrosis and warrants that these observations be further explored
in Phase 2 studies.
"We are pleased that our Phase 1 trial of GR-MD-02 in NASH
patients with advanced fibrosis was a success in all key measures
of safety and pharmacokinetics, while the exploratory marker A2M
and non-invasive liver stiffness measure via FibroScan® are
encouraging," said Peter G. Traber, M.D., Chief Executive Officer,
President and Chief Medical Officer of Galectin Therapeutics. "The
additional finding in the third cohort that liver stiffness may be
decreased following administration of GR-MD-02 is an exciting one
that opens additional avenues for Phase 2 study designs. The
results of the Phase 1 trial provide the basis for launching a
Phase 2 program that will include several concurrent trials focused
on NASH patients with advanced fibrosis and cirrhosis. We plan to
announce details of the Phase 2 program in February 2015 and to
initiate trials in the second quarter of 2015."
Dr. Traber added, "I extend sincere thanks to three groups for
their involvement in this study. First and most importantly, I
thank the patients who donated time and effort to help promote a
promising therapy – their dedication to our protocol is recognized
as critical to progress. Second, I thank the world-class group of
investigators and their support teams who worked on this trial.
Lastly, I thank Clinical Trial and Consulting Services, who as our
contract research partner worked tirelessly to accomplish these
results."
The Phase 1 multicenter, double-blind, placebo-controlled
clinical trial was conducted in patients with NASH with advanced
fibrosis (Brunt Stage 3) who received four doses of GR‑MD‑02 over a
35- to 42‑day period. Each of the three planned cohorts consisted
of patients randomized to receive active drug or placebo. Trial
design details can be found here.
GR-MD-02 is a complex carbohydrate drug that targets galectin-3,
a critical protein in the pathogenesis of fatty liver disease and
fibrosis. Galectin-3 plays a major role in diseases that involve
scaring of organs including fibrotic disorders of the liver, lung,
kidney, heart and vascular system. The drug binds to galectin
proteins and disrupts their function. Preclinical data in animals
have shown that GR-MD-02 has robust treatment effects in reversing
liver fibrosis and cirrhosis.
About Fatty Liver Disease with Advanced
Fibrosis
Non-alcoholic steatohepatitis (NASH), also known as fatty liver
disease, has become a common disease of the liver with the rise in
obesity rates. NASH is estimated to affect 9 to 15 million
people in the U.S., including children. Fatty liver disease is
characterized by the presence of fat in the liver along with
inflammation and damage in people who consume little or no alcohol.
Over time, patients with fatty liver disease can develop fibrosis,
or scarring of the liver, and it is estimated that as many as 3
million individuals will develop cirrhosis, a severe liver disease
where liver transplantation is the only treatment available.
Approximately 6,300 liver transplants are performed annually in the
U.S. There are no drug therapies approved for the treatment of
liver fibrosis.
About Galectin Therapeutics
Galectin Therapeutics is developing promising carbohydrate-based
therapies for the treatment of fibrotic liver disease and cancer
based on the Company's unique understanding of galectin proteins,
key mediators of biologic function. Galectin is leveraging
extensive scientific and development expertise as well as
established relationships with external sources to achieve
cost-effective and efficient development. The Company is pursuing a
clear development pathway to clinical enhancement and
commercialization for its lead compounds in liver fibrosis and
cancer. Additional information is available at
www.galectintherapeutics.com.
Forward Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. These statements relate to future events or future financial
performance, and use words such as "may," "estimate," "could,"
"expect" and others. They are based on management's current
expectations and are subject to factors and uncertainties that
could cause actual results to differ materially from those
described in the statements. These statements include those
regarding the hope that Galectin's development program for GR-MD-02
will lead to the first therapy for the treatment of fatty liver
disease with fibrosis. Factors that could cause actual performance
to differ materially from those discussed in the forward-looking
statements include, among others, that Galectin may not be
successful in developing effective treatments and/or obtaining the
requisite approvals for the use of GR-MD-02 or any of its other
drugs in development. The Company's current clinical trial and any
future clinical studies may not produce positive results in a
timely fashion, if at all, and could prove time consuming and
costly. Plans regarding development, approval and marketing of any
of Galectin's drugs are subject to change at any time based on the
changing needs of the Company as determined by management and
regulatory agencies. Regardless of the results of any of its
development programs, Galectin may be unsuccessful in developing
partnerships with other companies that would allow it to further
develop and/or fund any studies or trials. Galectin has
incurred operating losses since inception, and its ability to
successfully develop and market drugs may be impacted by its
ability to manage costs and finance continuing operations. For a
discussion of additional factors impacting Galectin's business, see
the Company's Annual Report on Form 10-K for the year ended
December 31, 2013, and subsequent filings with the SEC. You should
not place undue reliance on forward-looking statements. Although
subsequent events may cause its views to change, management
disclaims any obligation to update forward-looking statements.
CONTACT: Galectin Therapeutics Inc.
Peter G. Traber, M.D.
President, CEO & CMO
(678) 620-3186
ir@galectintherapeutics.com
LHA
Kim Golodetz
(212) 838-3777
kgolodetz@lhai.com
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