THE WOODLANDS, Texas,
Dec. 1, 2015 /PRNewswire/
-- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX)
announced today that top-line data from its TELECAST Phase 3
study showed results of telotristat etiprate in treating carcinoid
syndrome in cancer patients with metastatic neuroendocrine tumors
consistent with the clinical benefit observed in its pivotal
TELESTAR study. The TELECAST study was designed as a
companion to TELESTAR primarily to provide additional safety
exposure while further evaluating telotristat etiprate's activity
in carcinoid syndrome. TELECAST mostly enrolled patients
treated with somatostatin analog (SSA) therapy, the current
standard of care, with carcinoid syndrome characterized by less
severe bowel movement frequency than those patients in the TELESTAR
study, together with a smaller number of carcinoid syndrome
patients not treated with SSA therapy.
Telotristat etiprate met the study's primary efficacy endpoint,
the percent change from baseline in urinary 5-hydroxyindoleacetic
acid (5-HIAA, the main metabolite of serotonin) at week 12, the
final week of the double-blind treatment portion of the study
(p<0.001 for both dose arms compared to placebo). In
addition, despite the lower baseline bowel movement frequency than
in TELESTAR, telotristat etiprate achieved statistically
significant reductions in daily bowel movement frequency over the
12 weeks of the study (p=0.004 for the 250 mg dose arm and
p<0.001 for the 500 mg dose arm compared to placebo).
Safety and tolerability was one of the primary objectives of
the TELECAST study, and telotristat etiprate was well tolerated
during the double-blind treatment period, with profiles similar to
placebo for both the 250 mg and 500 mg dose arms and no overall
differences observed in gastrointestinal disorders or psychiatric
disorders, including changes in mood.
"We are very pleased with the efficacy and safety results of
telotristat etiprate in this study, notably including evidence of
benefit in a patient population whose bowel movement frequency was
lower at baseline than was the case in TELESTAR," said Lexicon
Executive Vice President and Chief Medical Officer Pablo Lapuerta, M.D. "TELECAST was intended to
complement our pivotal Phase 3 trial, TELESTAR. We now have
experience in more than 200 patients with carcinoid syndrome, with
TELECAST contributing consistent efficacy data and favorable safety
results. The data further support that the compound is acting
directly on the cause of carcinoid syndrome, by reducing serotonin
production within tumor cells."
Carcinoid syndrome is a rare disease affecting thousands of
cancer patients with metastatic neuroendocrine tumors (mNETs) that
have spread to the liver and other organs from the gastrointestinal
tract. The condition is characterized by frequent and debilitating
diarrhea that often prevents patients from leading active,
predictable lives, as well as by facial flushing, abdominal pain,
fatigue and, over time, heart valve damage.
Results from Lexicon's pivotal TELESTAR Phase 3 study were
presented earlier this year at the European Cancer Conference and
the annual symposium of the North American Neuroendocrine Tumor
Society.
TELECAST Results
The double-blind TELECAST study enrolled 76 patients with or
without concomitant SSA therapy provided they qualified based on at
least one sign/symptom of carcinoid syndrome, such as at least two
episodes of flushing per day, elevated urinary 5-HIAA at baseline,
or nausea present on at least one out of five days at
baseline. Patients who were not receiving SSA therapy could
also qualify for the study based on experiencing at least four
bowel movements per day as their sign/symptom. The three-arm
study evaluated two doses of oral telotristat etiprate – 250 mg and
500 mg, each taken three times daily – against placebo over a
12-week period with primary outcome measures consisting of safety
and the percent change from baseline in urinary 5-HIAA, and
secondary outcome measures including change from baseline in the
number of daily bowel movements. Patients in both the treatment and
placebo arms who were on SSA therapy at baseline continued their
SSA therapy throughout the study.
Data showed that patients treated with telotristat etiprate at
both the 250 mg and 500 mg doses experienced a statistically
significant percent reduction from baseline compared to placebo in
urinary 5-HIAA, the main metabolite of serotonin, at week 12, the
final week of the double-blind treatment portion of the study
(p<0.001), meeting the study's primary efficacy endpoint.
In addition, data showed that patients treated with telotristat
etiprate at both the 250 mg and 500 mg doses experienced a
statistically significant percent reduction from baseline compared
to placebo in the average number of daily bowel movements over the
12 weeks of the study (p=0.004 for the 250 mg dose arm and
p<0.001 for the 500 mg dose arm compared to placebo).
Treatment with telotristat etiprate was well tolerated during
the double-blind treatment period. The proportions of
patients with treatment-emergent adverse events (AEs) were 100% in
the 250 mg arm, 84% in the 500 mg arm and 81% in the placebo group
during the 12-week study period. The proportions of patients
with serious AEs (none of which were deemed related to treatment)
were 4% in the 250 mg arm, 8% in the 500 mg arm and 19% in the
placebo group. The proportions of patients who discontinued
treatment due to AEs were 8% in the 250 mg arm, 0% in the 500 mg
arm and 4% in the placebo group. Notably, in terms of
pre-defined AEs of special interest, both doses of telotristat
etiprate appeared similar to placebo, with three patients
experiencing nausea in the 250 mg arm, two in the 500 mg arm and
four in the placebo group, and one patient experiencing depression
or depressed mood in each of the 250 mg and 500 mg arms and two in
the placebo group.
About Telotristat Etiprate
Discovered using Lexicon's unique approach to gene science,
telotristat etiprate is the first investigational drug in clinical
studies to target tryptophan hydroxylase, an enzyme that triggers
the excess serotonin production within mNET cells that leads to
carcinoid syndrome. While existing treatments for carcinoid
syndrome work to reduce the release of serotonin outside tumor
cells, telotristat etiprate works at the source to reduce serotonin
production within the tumor cells. By specifically inhibiting
serotonin production, telotristat etiprate seeks to control this
important driver of carcinoid syndrome and, in turn, provide
patients with more control over their disease.
Telotristat etiprate has received Fast Track and Orphan Drug
designation from the U.S. Food and Drug Administration.
Lexicon retains rights to market telotristat etiprate in the
U.S. and Japan, and is building
the in-house commercial infrastructure to serve the U.S. market.
Lexicon has a license and collaboration agreement with Ipsen to
commercialize telotristat etiprate in Europe and other countries outside the U.S.
and Japan.
About Lexicon
Lexicon is a fully integrated biopharmaceutical company that is
applying a unique approach to gene science based on Nobel
Prize-winning technology to discover and develop precise medicines
for patients with serious, chronic conditions. Through its
Genome5000™ program, Lexicon scientists have studied the role and
function of nearly 5,000 genes over the last 20 years and have
identified more than 100 protein targets with significant
therapeutic potential in a range of diseases. Through the precise
targeting of these proteins, Lexicon is pioneering the discovery
and development of innovative medicines to safely and effectively
treat disease. Lexicon has a pipeline of promising drug candidates
in clinical and pre-clinical development in oncology, diabetes and
metabolism. For additional information please visit
www.lexpharma.com.
Safe Harbor Statement
This press release contains "forward-looking statements,"
including statements relating to Lexicon's clinical development of
telotristat etiprate (LX1032) and the results of and projected
timing of clinical trials and the potential therapeutic and
commercial potential of telotristat etiprate. In addition,
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 the risk that clinical studies of
telotristat etiprate may be halted, delayed or otherwise not
demonstrate safety or efficacy, the risk that Lexicon and its
licensees may be unable to file for regulatory approval of
telotristat etiprate with the FDA and other regulatory authorities
in accordance with its currently anticipated timelines, the risk
that the FDA and other regulatory authorities may not grant
regulatory approval of telotristat etiprate in accordance with
Lexicon's currently anticipated timelines or at all, and the risk
that such regulatory approvals, if granted, may have significant
limitations on the approved use of telotristat etiprate. As a
result, telotristat etiprate may never be successfully
commercialized. Other risks include Lexicon's ability to meet
its capital requirements, successfully conduct preclinical
and clinical development and obtain necessary regulatory
approvals of its other potential drug candidates, 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. Any of these risks, uncertainties and other
factors 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 "Risk Factors" in Lexicon's
annual report on Form 10-K for the year ended December 31, 2014, 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.
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SOURCE Lexicon Pharmaceuticals, Inc.