THE WOODLANDS, Texas,
Dec. 14, 2010 /PRNewswire-FirstCall/
-- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), a
biopharmaceutical company focused on discovering breakthrough
treatments for human disease, announced top-line results from a
recently completed Phase 2a study of LX2931 in patients with
rheumatoid arthritis (RA). LX2931 is an orally-delivered,
small molecule drug candidate that inhibits sphingosine-1-phosphate
(S1P) lyase, an enzyme important for modulating the immune system
by controlling S1P levels in lymphoid tissues. The trial was the
first test of this new anti-inflammatory mechanism of action in
patients and was designed to obtain safety and tolerability
information and signals of efficacy.
Results from the 12-week, randomized, double-blind,
placebo-controlled study in 208 patients with RA demonstrated that
all three doses tested, 70 mg, 110 mg, and 150 mg given once per
day, were well tolerated over the 12-week treatment period.
Taken together, the data also suggested that patients treated
with 150 mg once daily of LX2931 showed an improvement in the
primary efficacy endpoint, the percentage of patients achieving an
American College of Rheumatology 20 (ACR20) response at week 12
(60% versus 49% for placebo). Patients treated with 70 mg or
110 mg once daily did not indicate improvement in the ACR20 at week
12 (44% and 41% response rates, respectively) relative to placebo.
Adverse events for all three LX2931 dose groups were predominantly
mild-to-moderate, with frequencies similar to the placebo
group.
"We believe the preliminary signal of efficacy and the favorable
safety profile observed in this trial supports further study of
additional higher doses of LX2931 as an orally-delivered treatment
for rheumatoid arthritis," said Dr. Arthur T. Sands, president and
chief executive officer of Lexicon. "While we were
disappointed by the unusually high placebo effect in this trial, we
are encouraged by the excellent overall safety profile observed in
the first test of this new mechanism of action in patients with
RA."
The company intends to commence discussions with potential
pharmaceutical partners to pursue further development of LX2931 in
rheumatoid arthritis.
Clinical Trial
The recently completed study was a 12-week, randomized,
double-blind, placebo-controlled study in 208 patients on stable
dose methotrexate with progressing rheumatoid arthritis. Patients
were randomized to receive either placebo (n=49) or LX2931, 70 mg
(n=55), 110 mg (n=54), or 150 mg (n=50), once daily for 12 weeks.
In addition to measurements to assess the drug's safety,
efficacy endpoints included the primary endpoint, ACR20 at week 12,
as well as secondary endpoints of ACR20, ACR50, ACR70 and DAS28 at
weeks 4, 8 and 12. The trial was conducted at sites within
the United States and Eastern Europe.
About S1P Lyase and the Role of S1P in Autoimmune
Disease
S1P lyase is responsible for the irreversible degradation of
S1P, a biologically active lipid that can act as a second messenger
in signal transduction pathways important for immune function.
Changes in local S1P concentrations and gradients in immune
tissues can modify lymphocyte migration, inflammatory cell
response, and affect barrier function of endothelial cells.
Inhibiting S1P lyase results in an increase in S1P levels,
primarily in lymphoid tissues. The physiological outcome of
raising S1P levels in the lymphoid system is immune-modulation,
which offers new opportunities for treating autoimmune and
inflammatory diseases.
About Lexicon
Lexicon is a biopharmaceutical company focused on discovering
breakthrough treatments for human disease. Lexicon currently
has four drug candidates in mid-stage development for diabetes,
irritable bowel syndrome, carcinoid syndrome and rheumatoid
arthritis, all of which were discovered by Lexicon's research team.
Lexicon has used its proprietary gene knockout technology to
identify more than 100 promising drug targets. Lexicon has
focused drug discovery efforts on these biologically-validated
targets to create its extensive pipeline of clinical and
preclinical programs.
In addition to LX2931, Lexicon has three other drug candidates
progressing through Phase 2 clinical trials: LX4211, an
orally-delivered, once-daily, dual inhibitor of sodium glucose
transporter 1 (SGLT1) and SGLT2 for type 2 diabetes; LX1031, a
locally-acting serotonin synthesis inhibitor for irritable bowel
syndrome; and LX1032, a peripherally-available serotonin synthesis
inhibitor for carcinoid syndrome. For additional information
about Lexicon and its programs, please visit www.lexpharma.com.
Safe Harbor Statement
This press release contains "forward-looking statements,"
including statements relating to the characterization of the
safety profile of LX2931 observed in the Phase 2 clinical trial as
favorable, the characterization of the results of the Phase 2
clinical trial of LX2931 as demonstrating a preliminary signal of
efficacy and supporting further study as a potential treatment for
rheumatoid arthritis, the mechanism of action of LX2931, and the
potential therapeutic and commercial potential of LX2931
generally. This press release also contains forward-looking
statements relating to Lexicon's growth and future operating
results, discovery and development of products, strategic alliances
and intellectual property, as well as other matters that are not
historical facts or information. All forward-looking
statements are based on management's current assumptions and
expectations and involve risks, uncertainties and other important
factors, specifically including those relating to Lexicon's
ability to successfully conduct clinical development of LX2931 and
preclinical and clinical development of its other potential drug
candidates, advance additional candidates into preclinical and
clinical development, obtain necessary regulatory approvals,
achieve its operational objectives, obtain patent protection for
its discoveries and establish strategic alliances, as well as
additional factors relating to manufacturing, intellectual property
rights, and the therapeutic or commercial value of its drug
candidates, that may cause Lexicon's actual results to be
materially different from any future results expressed or implied
by such forward-looking statements. Information identifying
such important factors is contained under "Factors Affecting
Forward-Looking Statements" and "Risk Factors" in Lexicon's annual
report on Form 10-K for the year ended December 31, 2009, as filed with the Securities
and Exchange Commission. Lexicon undertakes no obligation to
update or revise any such forward-looking statements, whether as a
result of new information, future events or otherwise.
SOURCE Lexicon Pharmaceuticals, Inc.