THE WOODLANDS, Texas,
Oct. 12, 2012 /PRNewswire/
-- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), a
biopharmaceutical company focused on discovering breakthrough
treatments for human disease, announced positive, top-line data
from a recently completed Phase 2 study in carcinoid syndrome with
telotristat etiprate. Results from the trial will be presented at
the North American Neuroendocrine Tumor Society on Saturday, October 13, 2012 in San Diego, California.
Carcinoid syndrome is a chronic condition caused by
neuroendocrine tumors that usually originate from the
gastrointestinal tract. It is characterized by severe diarrhea and
flushing episodes with long-term consequences including
malnutrition, heart disease, and death. Carcinoid syndrome has been
linked to excess production of serotonin by metastatic tumor cells.
Telotristat etiprate is an oral investigational new drug designed
to treat carcinoid syndrome by reducing serotonin production in
patients with metastatic carcinoid tumors. Telotristat
etiprate has Fast Track status and Orphan Drug designation from the
Food and Drug Administration, and Orphan Drug designation from the
European Medicines Agency.
The primary efficacy endpoint of the trial was the reduction of
bowel movements from baseline in patients with metastatic carcinoid
syndrome who were refractory to or could not tolerate somatostatin
analog therapy. Patients experienced a 46.4% median reduction from
baseline at week 12, with the number of daily bowel movements
steadily decreasing over time. All observed changes from baseline
were statistically significant at p < 0.001. This change
corresponded with an increased proportion of patients reporting
adequate relief of their carcinoid symptoms, a global assessment
which also improved over time, with 75% of the patients with data
at week 12 reporting improvement. Clinically relevant decreases
from baseline were likewise seen for a number of key secondary
endpoints, including statistically significant improvements in
stool consistency (p < 0.001) and trends of reductions in
abdominal pain (p=0.09) and the number of cutaneous flushing
episodes (p=0.052). The median percentage reductions from baseline
of urinary 5-HIAA at weeks 8 and 12 were 68.3% (p=0.019) and 72.7%
(p=0.031), respectively. Urinary 5-HIAA is a biomarker of serotonin
synthesis and is of key interest in these patients.
"In this trial, telotristat etiprate provided rapid and durable
benefit across several dimensions of carcinoid syndrome, a
devastating metastatic cancer syndrome with few treatment options
for patients," said Dr. Pablo
Lapuerta, Lexicon's senior vice president and chief medical
officer. "Of additional interest was improvement seen in two
patients who were not on background somatostatin analog therapy,
the only currently-approved treatment."
The open-label, dose-escalation study was conducted in
Europe in 15 patients with
metastatic carcinoid syndrome who were refractory to or could not
tolerate somatostatin analog therapy. Efficacy measures included
change in bowel movement frequency, relief of symptoms, and
reduction in serotonin synthesis. Patients received ascending doses
of 150 mg, 250 mg, 350 mg and 500 mg of telotristat etiprate,
administered three times daily (TID), for 14 days on each dose
until reaching a maximal dose, which was then continued until the
completion of 12 weeks of therapy. Escalation to a higher dose was
contingent on tolerability and clinical response. Fourteen patients
(93%) completed the trial, and 12 of these 14 patients were treated
with 500 mg TID of study drug during the last four weeks of the
treatment period. The one patient who discontinued early withdrew
from the 350mg TID dose level for reasons not related to drug
safety. Notably, the two patients in the study who were not
receiving background somatostatin analog therapy observed
reductions in bowel movements of 67% and 48% from baseline to week
12.
Telotristat etiprate was well tolerated. There was no evidence
of dose–limiting toxicity, and no patient discontinued from the
study early due to an adverse event. Only three patients reported a
serious adverse event, none of which was related to study drug.
"The positive results from this second Phase 2 trial of
telotristat etiprate further support its potential utility in the
treatment of carcinoid syndrome in a population that is refractory
to or cannot tolerate current therapies," said Dr. Arthur T. Sands, Lexicon's president and chief
executive officer. "Building upon results from our previously
reported placebo-controlled four-week Phase 2 trial, this study
showed strongly positive results in multiple parameters over twelve
weeks of therapy, the same treatment period in our upcoming
registrational, Phase 3 clinical trial."
About Telotristat Etiprate (LX1032)
Telotristat etiprate was discovered and developed at Lexicon to
reduce serotonin production by inhibiting tryptophan hydroxylase
(TPH), a key enzyme in the synthesis of serotonin. Excessive
levels of serotonin have been associated with carcinoid syndrome,
especially diarrhea and carcinoid heart disease. Serotonin's
breakdown product, 5-HIAA, is a biomarker used in the diagnosis of
the condition. In preclinical studies, telotristat etiprate
reduced 5-HIAA and peripheral serotonin in several different
species without affecting serotonin levels in the brain.
Telotristat etiprate is being developed under Fast Track and
Orphan Drug designation from the U.S. Food and Drug Administration
and Orphan Drug designation from the European Medicines Agency.
Telotristat etiprate is a member of a new class of oral drugs
invented by Lexicon, the serotonin synthesis inhibitors, which are
being developed in a spectrum of gastrointestinal
indications. Lexicon is also currently carrying out a Phase 2
trial of telotristat etiprate in mild to moderate ulcerative
colitis.
About Carcinoid Syndrome
Carcinoid syndrome is a chronic condition caused by metastatic
neuroendocrine tumors that usually originate from the
gastrointestinal tract. Patients with carcinoid syndrome
currently have limited therapeutic options, and the standard of
care includes chronic therapy with somatostatin analogs, which are
delivered by injection. With current therapy, carcinoid
syndrome symptoms return over time in most patients, hence the need
for new agents.
About Lexicon
Lexicon is a biopharmaceutical company focused on discovering
breakthrough treatments for human disease. Lexicon currently has
four drug programs in mid-stage development for diabetes, carcinoid
syndrome, irritable bowel 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. 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 Lexicon's clinical development of
telotristat etiprate (LX1032), including characterizations of the
results of and projected timing of clinical trials, and the
potential therapeutic and commercial potential of telotristat
etiprate. 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 telotristat
etiprate 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.
Unless specifically indicated otherwise, results reported as trends
were not statistically significant. 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, 2011, 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.